Korean Journal of Biological Psychiatry

At the beginning, researches on the biology of depression or affective illness have focused mainly on the receptor functions and neuroendocrine activities. And the studies of the past years did not break new theoretical background, but the recent advances in the research on the molecular mechanisms underlying neural communication and signal transduction do add some insights to many established ideas. This article will overview some of the more recent advances in the clinical researches of depression. Our major concerns to be presented here include the followings：(1) alterations in the post-synaptic neural transduction；(2) changes in the neurons of hypothalamic neuropeptides；(3) decreased peptidase enzyme activities；(4) associations of hypothalamic-pituitary-adrenal axis abnormalities with serotonin neurotransmission；(5) role of serotonin transporter；(6) changes in the responsiveness of intracellular calcium ion levels；(7) the inositol deficiency theory of lithium and depression；(8) the transcription factors including immediate early genes；(9) recent genetic studies in some families. This brief overview will suggest that changes in DNA occur during antidepressant therapy. These changes at the DNA level initiating a cascade of events underlying antidepressant modality will give us the insights on the molecular biological basis of the pathogenesis of depression and cues for a new class of antidepressants.

Depression;Neurobiology;Serotonin;Neuropeptide;Enzyme.

In order to understand the pathogenesis and progression of some synaptic loss related neuropsychiatric diseases, We attempted to develop a computer model in this study. We made a simple autoassociative memory network remembering numbers, transformed it into a disease model by pruning synapses, and measured its memory performance as a function of synaptic deletion. Decline in performance was measured as amount of synaptic loss increases and its mode of decline is sudden or gradual according to the mode of synaptic pruning. The developed computer model demonstrated how synaptic loss could cause memory impairment through a series of computer simulations, and suggested a new way of research in neuropsychiatry.

Computer model;Dementia;Neural network;Schizophrenia;Synapse.

Traumatic Brain Injury(TBI) of any severity can result in broad and persisting biopsychosocial sequelae. Depression after TBI occur at a greater frequency than in the general population, with estimates approaching 25% to 50% for major depression, and 155 to 30% for dysthmia. Acute onset depressions are related to lesion location and may have their etiology in biological response of the injured brain, whereas delayed onset depressions may be mediated by psychosocial factors, suggesting psychological reactions as a possible mechanism. Anxious depressions are associated with right hemisphere lesions, whereas major depressions alone are associated with left dorsolateral frontal and left basal ganglia lesions. However, there is insufficient information to postulate a specific neuroanatomic model for TBI-related depression.

Brain injury;Head injury;Depression.

While depression is certainly a prevalent disorder, it is often severe and debilitating and does not always have the good prognosis we have been led to expect. Social approaches to affective disorders have not been subjected to the same level of scrutiny as the interventions used in the management of schizophrenia. Psychosocial Rehabilitation is now at a critical stage. Psychoeducation, social skill training, cognitive remediation, family education, vocational rehabilitation and case management programs are essential for the rehabilitation of chronic depression.

Chronic depression;Biopsychosocial model;Psychosocial rehabilitation.

New antidepressants have become available for clinical use in the 1990s. Before this decade, the drugs available to treat depression consisted essentially of monoamine oxidase inhibitors, tricyclic antidepressants, and lithium. Following the introduction of SSRIs, the options have expanded and now include SSRIs, nefazodone, venlafaxine, mirtazapine, reboxetine, tianeptine. Newer antidepressants possess a variety of pharmacological characteristics that are relevant to the choice of an antidepressant for clinical use. This review summarizes some of the major pharmacological characteristics among the drugs.

Depression;Newer antidepressants;SSRIs.

This review focused on the pharmacological treatment of alcoholism, eespeciallyalcoholism-related mental disorder. The pharmacological agent for alcoholism can be divided into the following categories：anticraving agent, aversive agent, agent to treat acute alcohol withdrawal, agent to diminish drinking by treating associated psychiatric pathology, agent to induce sobriety in intoxicated individuals. Following trends are included in new trends of pharmacological treatment of alcoholism. What are precise conditions amenable to pharmacological intervention?；How can psychosocial and behavioral intervention be integrated with pharmacotherapy to enhance treatment outcome?；Is the concept of “matching” specific pharmacotherapy treatment to different aspect of alcoholism more efficacious than a more generalized medicational approach to treatment? One of the most important factors for alcoholics treatment is good and proper therapeutic relationship with patients and setting up individually specialized treatment program is also important.

Pharmacological treatment;Alcohol dependence.

Polypharmacotherapy, both psychotropic and nonpsychotropic, is widespread in various situations including psychiatric hospitals and general hospitals. As the clinical practice of using more than one drug at a time increase, the clinician is faced with ever-increasing number of potential drug interactions. Although many interactions have little clinical significances, some may interfere with treatment or even be life-threatening. The objective of this review is evaluation for drug-drug interactions often encountered in psychiatric consultation. Drug interactions can be grouped into two principal subdivisions：pharmacokinetic and pharmacodynamic. These subgroups serve to focus attention on possible sites of interaction as a drug moves from the site of administration and absorption to its site of action. Pharmacokinetic processes are those that include transport to and from the receptor site and consist of absorption, distribution on body tissue, plasma protein binding, metabolism, and excretion. Pharmacodynamic interactions occur at biologically active sites. In psychiatric consultation, these two subdivisions of drug interactions between psychotropic drugs and other drugs are likely to happen. We gathered informations of the drugs used in physically ill patients who are consulted to psychiatric department in Korea University Hospital. And we reviewed the related literatures about the drug-drug interactions between psychotropic drugs and other drugs.

Drug-drug interaction;Psychotropic agents;Cytochrome P450(CYP);Physically ill patients.

The cAMP-dependent protein kinase(PKA) is an intracellular enzyme with serine-threonine kinase activity that plays a key role in cell growth, differentiation, and apoptosis in eukaryotes. In order to understand the PKA signal transduction pathway regulating cell life cycle and identify its role, we focused on the characterization of up-/down-regulated genes by PKA using the differential display polymerase chain reaction. Seven differentially expressed sequence tags(DEST) have been obtained. Among these DESTs, 2 DESTs were homologous to the sequence of genes from BLAST search result. KC1-5 DEST that was up-regulated in A123.7 cells was highly corresponded to mouse apoptosis-related gene(MA-3) or mouse mRNA for topoisomerase inhibitor suppressed(TIS). MA-3 was induced in various types of apoptosis, specially in NGF-deprived apoptotic PC12 cells. TIS was down-regulated in the RVC lymphoma cells incubated with topoisomerase inhibitor that induces DNA strand breakages. PG1-1 DEST that was highly expressed in PC12 cells was corresponded to transposon Tn10 3'-end. Tnansposon Tn10 was up-regulated in differentiated myeloblastic ML-1 cells by 12-O-tetradecanoylphorbol-13-acetate. This study illuminates that MA-3/TIS was down-regulated by PKA activity, and transposon Tn10 was up-regulated by it.

cAMP-dependent protein kinase(PKA);A123.7 cell;PC12 cell;DD-PCR.

This study was performed to investigate the mechanism of the clozapine-induced seizures in partially restrained rats by concomitant treatment with drugs affecting monoaminergic systems. Partially restrained rats treated with acute single doses of 10mg/kg clozapine exhibited myoclonic jerks(MJs). Drugs affecting the monoaminergic systems, including 2mg/kg haloperidol, 5mg/kg propranolol, 2mg/kg ritanserin, 20mg/kg fluoxetine, and 20mg/kg imipramine, were concomitantly treated with clozapine to observe the effects of these drugs on the MJs. The drugs were given intraperitoneally either as acute single doses(haloperidol, propranolol, ritanserin, and fluoxetine) or as chronic doses for 21days(haloperidol, imipramine, ritanserin, and fluoxetine). The effects of the concomitant treatment of other drugs on the clozapine-induced MJs were evaluated by comparison of the total numbers of the MJs between the clozapine-treated and concomitantly treated groups. The results were as follows. 1) Concomitant treatment with acute single doses of haloperidol, propranolol, and fluoxetine reduced the total numbers of the clozapine-induced MJs, while concomitant treatment with ritanserin did not. 2) Concomitant treatment with chronic doses of imipramine and ritanserin increased the total numbers of the MJs, while concomitant treatment with fluoxetine reduced them. Concomitant chronic treatment with haloperidol did not affect the numbers of the MJs. These results suggest that dopamine and serotonin, not noradrenalin may be involved in the clozapine-induced MJs in partially restrained rats. Future research needs to study the function of each subtype of monoaminergic receptors on the mechanism of the clozapine-induced seizure.

Clozapine;Myoclonic Jerk;Dopamine;Serotonin;Noradrenalin;Monoamine.

Objectives：Significant progress has been made in understanding psychosocial, psychological, and environmental factors associated with suicide. However it is only recently that attention has been paid to the understanding of the neurobiology of suicide. The aim of this study was to examine the relationship between platelet serotonin level and suicidal behavior and psychological features of the suicidal attempters.

Methods：After a suicidal attempt platelet serotonin level was measured from 21patients and compared it with those from depression patients and normal controls. Also MMPI, HAM-D, Barratt impulsiveness scale(BIS) were done to evaluate their psychological features.

Results：1) There was no significant difference in sex ratio of the suicidal attempters. 2) There was no significant difference in platelet serotonin levels among three groups. 3) The analysis of MMPI revealed that the scores of D, Hs, Pt in clinical scales were significantly higher in suicide patients and scores of D, Pa, Si were in depression patients. 4) The HAM-D score was significantly higher in depression and suicide patients, especially in depression patients. 5) The analysis of Barratt impulsiveness scale revealed that the scores of nonplanning, motor and cognitive impulsiveness scale were significantly higher in suicide patients.

Conclusions：There was no significant difference in platelet serotonin levels among three groups. However the analysis of psychological features revealed significant differences. Therefore we concluded that psychological examinations are benefit to evaluate the suicidal tendency.

Suicide;Serotonin;MMPI;HAM-D;BIS.

To understand a mechanism of underlying cognitive deficit in schizophrenia, the risk factors, cognitive function, blood dopamine concentrations and glutamate dehydrogenase activities of male schizophrenics with tardive dyskinesia(N＝30) were compared with those of schizophrenics without tardive dyskinesia(N＝30). The results were as following；1) The age, duration of illness and duration of medication were significantly more in schizophrenics with tardive dyskinesia than schizophrenics without tardive dyskinesia(respectively p<0.005, p<0.0001, p<0.0001). 2) The scores of MMSE, TIQ, VIQ and PIQ were significantly lower in schizophrenics with tardive dyskinesia than schizophrenics without tardive dyskinesia(rspectively p<0.0001). 3) Plasma dopamine concentrations were tended to be higher, and serum glutamate dehydrogenase activities were tended to be lower in schizophrenics with tardive dyskinesia than schizophrenics without tardive dyskinesia. 4) The cognitive deficit seemed to be negatively correlated with duration of illness and duration of medication(respectively γ＝-0.496, γ＝-0.615).

Schizophrenia;Tardive dyskinesia;Cognitive deficit.

Background：Since dysthymia begins in late childhood or adolescence and has a chronic course, long-term pharmacotherapy may be required. New generation antidepressant, moclobemide, with more acceptable side effect profiles, is effective in the treatment of dysthymia. The main objective of this study was to determine whether they exhibit comparable efficacy and tolerability in dysthymia to amitriptyline.

Method and Materials：The efficacy and tolerability of the moclobemide and amitriptyline, were compared in a eight-week single-centre double-blind study in patients(n＝37) with dysthymia using he HAMD-17, the Clinical Global Impression Scale(CGI), the Montgomery-Asberg Depression Rating Scale(MADRS), Efficacy Index-Therapeutic Index(EITE), 4-point Index Side Effect Scale(4-PISES), and Efficacy Index- Side Effect Scale(EISE).

Results：A total of 37 patients entered the study, 19 were randomly assigned to the moclobemide group and 18 to be amitriptyline group. Demographic and illness characteristics were similar in both groups. There were no significant difference between two groups at the total 17-HDRS score, the HAMD-17% improvement, the total MADRS score, CGI response, and the EITE. In the comparison of EISE between two groups, the scores of the moclobemide group were relatively lower than the amitriptylinen group in full treatment. And the differences were significant(moclobemide group 1.39±0.61；amitriptyline group 2.00±0.85, p<.001). At the 4-PISE, There was no serious or treatment threatening side effects. And there was no specific difference in side effects between two groups. The moclobemide group reported higher EIR scores than the amitriptyline group at every follow up day, but the differences were not significant. And, there was no significant differences in the scores of five HRQOL subcategories which is compared between two groups at every follow up days.

Conclusions：In terms of 17-HDRS and MADRS, moclobemide and amitriptyline are equally effective at least in allevating dysthymic symptoms. But moclobemide tended to be less troubling and better tolerated than amitriptyline. Therefore, moclobemide treatment can be used as a safe, and higher satisfactory treatment strategy for the dysthymia.

Dysthymia;Moclobemide;Amitriptyline;Efficacy;Tolerability.

Objectives：The alcohol dependence in elderly people has been prevalent because of increase in geriatric population. However, it is difficult to find out alcohol dependence in the aged, because they have less specific clinical features as compared with adult alcoholics. The aims of this study were to screen alcohol dependence among elderly Koreans and to know the clinical characteristics of Korean delerly alcoholics.

Methods：The questionnaires translated into Korean such as Michigan Alcoholism Screening Test(MAST-K), the Brief MAST and the MAST-Geriatirc Version(MAST-KG) were used to screen alcohol dependence in the elderly alcoholic inpatients aged over 60(N＝43), adult alcoholic inpatients within 20-59 Yrs of age(N＝60), which were compared with age matched normal healthy aged(N＝18) or adult controls(N＝45). The demographic data such as sex, age, education, occupation, socioeconomic status, marital status, numbers of children, dwelling and religion as well as alcohol history such as duration of alcohol drinking, onset age, family history, impulsivity, somatic illness and motivation were also obtained to identify characteristic features of Korean aged alcoholics by structured interviews.

Results：1) The aged alcoholics had the charateristic features of more in males, lower age, low education levels, more in blue-collar workers, lower socioeconomic class, more in single, few babies, more living alone, having no religion without statistical significance. 2) The onset age of alcohol dependence was significantly higher in the aged alcoholics(45.3±13.6Yrs) than in the adult alcoholics(27.7±8.7Yrs)(p<0.0001). The duration of problematic alcohol drinking was significantly longer in the aged alcoholics(22.0±15.1Yrs) than in adult alcoholics(14.2±8.4Yrs)(p<0.01). Otherwise, there were no significant difference between aged and adult alcoholics in the family history, imulsivity, somatic illness and motivation. 3) The mean score of the MAST-K was significantly higher in the aged alcoholics(20.6±5.4) than in the normal aged(6.7±4.4)(p<0.0001), which was significantly lower than in the adult alcoholics(26.2±8.0) and in normal adult controls(9.5±3.2)(p<0.05). The mean score of the Brief MAST was significantly lower in the aged alcoholics(9.3±3.5) than in the adult alcoholics(14.5±6.6)(p<0.0001). The mean score of the MAST-KG was significantly higher in the aged alcoholics(10.6±3.5) than in the normal aged(4.8±4.3)(p<0.0001). The former was significantly lower than in the adult alcoholics(12.9±4.3)(p<0.005), and the mean score was 4.5±2.8 in normal adult controls. 4) The items which showed statistically significant differences between aged alcoholics and normal aged controls could be found in 10 items of the MAST-K(items 2, 3, 4, 5, 11, 14, 17, 21, 22 and 23), 2 items of the Brief MAST(items 2 and 9), and 7 items of the MAST-KG(items 6, 13, 18, 19, 22, 23 and 24)(p<0.01).

Conclusions：The scores of the MAST-K, the Brief MAST and the MAST-KG were significantly lower in the aged alcoholics than those in the adult alcoholics(p<0.05). The statistically significant differences between aged alcoholics and normal aged controls could be found in 10 items of the MAST-K, 2 items of the Brief MAST and 7 items of the MAST-KG. Therefore, a briefer rating scales around 10 items are needed to screen alcohol dependence among Korean elderly people.

Aged alcoholics;Onset age;MAST-K;The Brief MAST;MAST-KG.

Objectives：There have been several evidences that the central nervous system defect is one of the etiologic factors in schizophrenia and high nailfold plexus visibility can reflect these defects indirectly. These are particularly related to the negative symptoms of schizophrenia. In this study, we examined the relationship between nailfold plexus visibility and various clinical variables in schizophrenia. 

Methods：Forty patients(20 males, 20 females) satisfying the DSM-lV criteria for schizophrenia and forty normal controls(20 males, 20 females) were measured for Plexus Visualization Score (PVS) by using capillary microscopic examination. We used Positive and Negative Syndrome Scale(PANSS), Ulmann-Giovannoni Process-Reactive Questionnaire(PRQ), Phillips Premorbid Adjustment Scale(PAS), Continuous Performance Test, and Backward Masking for psychopathology and clinical variables. 

Results：There was no significant relationship between schizophrenic subjects and normal controls in PVS. PVS was correlated with PANSS positively except negative symptom subscore. PVS was correlated with PRQ score negatively, and with PAS score positively. 

Conclusions：This study shows high PVS are associated with more severe psychotic symptoms and with clinical variables, such as disease process and premorbid adjustment, in some schizophrenics.

Schizophrenia;Plexus visualization score;Negative symptoms.

This study was done to examine whether cigarette smoking improved smooth pursuit eye movement(SPEM) abnormalities in chronic schizophrenic inpatients. Fifteen schizophrenic and twelve alcoholic subjects abstained from their usual cigarette smoking for a minimum of nine hours and their baseline performances during the constant velocity smooth pursuit tasks were assessed. Then, the subjects smoked as much as they desired in a 10 minutes period and were retested immediately after smoking and 15 minutes after smoking. Electrooculographic recordings during the eye movements were converted and saved as digitized files. Power spectral density curves and natural logarithm value of signal/noise(Ln S/N) ratios were computed from them. In the schizophrenic patients, Ln S/N ratios increased significantly immediately after smoking compared to baseline. But, Ln S/N ratios showed no statistically significant changes after 15 minutes compared to baseline. In alcoholic subjects, Ln S/N ratios showed no statistically significant changes immediately after smoking and after 15 minutes compared to baseline. In conclusion, SPEM was improved in schizophrenic patients immediately after smoking and we hypothesized that nicotinic receptor dysfunction maybe a candidate mechanism for smooth pursuit eye movement abnormalities in schizophrenia.

Cigarette smoking;Nicotine;SPEM(Smooth Pursuit Eye Movement);Ln S/N ratio;Schizophrenia;Alcoholism.

The purposes of this study were to test the negative association between schizophrenia and rheumatoid arthritis(RA) and to clarify the role of prolactin and estrogen as protective factors in this association. The author compared the prevalence rate of RA between 561 patients with schizophrenia and 222 patients with mood disorder. For investigating the role of estrogen and prolactin, the author checked the plasma prolactin and estradiol level in 80 patients with paranoid schizophrenia and 77 patients with RA. The results were as follows. 1) Epidemiological data The prevalence rate of RA in the schizophrenic group was 0/561 and that of RA in the mood disorder group was 2/222. To compare these results between two groups, the author applied the Binomial test using the average prevalence rate of RA(0.8%) in the general population as a reference rate. The prevalence rate of RA in the schizophrenic group was significantly lower than that of RA in the general population. However, the prevalence rate of RA in the mood disorder group was not significantly different to that of RA in the general population. 2) Comparison of plasma prolactin and estradiol level between two groups The plasma level of prolactin in the schizophrenic group was significantly higher than that of prolactin in the RA group(p＝0.000). However, the plasma level of estradiol in the schizophrenic group was significantly lower than that of estradiol in the RA group(p＝0.017). These results were not consistent across gender. To contrast with the results in the female group, which were consistent with the results in the total subjects, for the male group, the plasma levels of prolactin and estradiol in the schizophrenic group were significantly higher than those of prolactin and estradiol in the RA group. These results support the results of previous studies which confirm the negative association between schizophrenia and RA. These results also suggest that the elevation of plasma prolactin level in the patients with schizophrenia has a antirheumatic effect while the elevation of plasma estradiol level in the patients with RA has a anti-schizophrenic effect, and that these effects act as a possible mechanism in the negative association between two disorders. However, these results suggest that this association is specific to female patients.

Schizophrenia;Rheumatoid arthritis;Negative association;Prolactin;Estrogen.

The authors described a case of male schizophrenia who developed myoclonic jerk repeatedly and one episode of convulsive seizure during the treatment of clozapine. According to literatures and reported cases, myoclonic jerks induced in a small amount of clozapine may precede and predict the development of a convulsive seizure. Therefore clinicians have to pay attention to the development of a myoclonic jerk during the administration of clozapine. They may decrease the dosage of clozapine step by step at first in the convulsive state, and observe EEG changes of patients frequently.

Clozapine;Myoclonic jerk;Convulsive seizure.

Transgenic mice models of Alzheimer's disease were produced by overexpressing APP(amyloid precursor protein) mutant and presenilin mutant genes using the promotors that induced neuronal expression. The neuropathologies, electrophysiological changes and behavioral changes that were demonstrated in these transgenic mice models were amyloid changes, gliotic changes, A-beta increases, deficit in LTP(long-term potentiation) and behavioral changes. Some or all of the above changes were found in each transgenic mice model. These models generally showed amyloid neuropathology but they usually lacked the neurofibrillary tangles. So, they can be regarded as partial models of Alzheimer's disease. The development of them is undoubtedly the great progress toward future research.

Alzheimer's dementia;Transgenic mice;APP;PS.

Animal models can provide a useful tool for the study of some aspects of psychiatricdisorders and their treatment. The four criteria for the evaluation of animal models ofpsychiatric disorders are as following：1) similarity of inducing conditions 2) similarityof behavioral state 3) common underlying neurobiological mechanisms 4) reversal by clinically effective treatment techniques. Several animal models have been proposed for schizophrenia：phenylethylamine model, L-dopa model, hallucinogen model, cocaine model, amphetamine model, phencyclidinemodel, noradrenergic reward system lesion model, reticular stimulation model, social isolation model, conditioned avoidance reaction, catalepsy test, paw test, self-stimulation paradigms, latent inhibition paradigms, blocking paradigms, prepulse inhibition of the startle reflex, rodent interaction, social behavior in monkeys, hippocampal damage, high ambient pressure, and models using selective breeding. Among them, animals with bilateral lesion of the hippocampus may provide an adequate animal model for several symptoms of schizophrenia, and ketamine model can reproduce negative symptoms and cognitive deficits as well as positive symptoms of schizophrenia. In conclusion, no model of schizophrenia is entirely representative of the disease, andfindings gleaned from model systems must be cautiously interpreted. Furthermore,the process of developing and validating animal models must work in concert with theprocess to identify reliable measures of human phenomenology.

Schizophrenia;Latent inhibition paradigm;Hippocampal lesion model;Ketamine model;Models using selective breeding.

There are a number of approaches in developing experimental models for depression, but there is no such thing as a best model for depressive syndrome. Animal models are subject to the obvious limitations inherent in the assumption that human psychopathology can be represented accurately in lower animals. Recently, the concern increasingly is to develop a variety of experimental paradigms in animals to study selected aspects of human psychopathology, and animal models should be understood as basically experimental preparations that are developed to carry out these objects. Therefore, a battery of a variety of animal models should be applied to permit detailed pathophysiological studies and to develop new antidepressant treatments. Animal models of depression basically consider behavioral isomorphism with the human depression a plus, but not a requirement, and the model behavior should be defined operationally in order to be reproduced reliably by other researchers and be responsive to those agents possessing demonstrated clinical efficacy in human depression.In conclusion, animal models of depression have played a significant role in elucidating pathophysiology of depression and developing current treatments for depression, but there is no single comprehensive model for depression until now. Each of the proposed animal model has its advantages and limitations. In other words, certain paradigms are suitable for studying certain phenomena, whereas others are more suitable for studying other aspects. The best model for depression depends upon what the question is.

Depression;Animal model;Validity.

Until recently, the etiology of schizophrenia was generally attributed to abnormalities in dopaminergic neurotransmission. Specifically, an excess of dopaminergic activity in the mesolimbic system has been postulated to produce the positive symptoms, while decreased dopaminergic activity in the mesocortical system has been suggested to cause negative symptoms. Accordingly, we performed an association study of schizophrenia with TH gene. Three hundred and seventy four biologically unrelated schizophrenic patients meeting DSM-III-R criteria from Kangnam St. Mary's Hospital affiliated with Catholic university of Korea were recruited for our study. The 393 healthy controls were volunteers for DNA library of Kangnam St. Mary's Hospital without personal or family history of psychiatric and neurologic illness. DNA was extracted from peripheral mononuclear cells and polymorphic region was amplified by polymerase chain reaction. TH intron 1 VNTR polymorphism was typed by silver staining. The allele distributions of TH gene were not different between schizophrenics and controls. However, the frequency of allele A was significantly higher in positive group than that of negative group of schizophrenics. These findings suggest that poitive schizophrenia may be associated with allele A of TH gene.

Schizophrenia;Tyrosine hydroxylase;Genetics;Association.

Objective：The purpose of this study was to evaluate the effects of alcohol on neurocognitive function, psychomotor performance and subjective response in healthy Korean adults with different ALDH2 genotypes.

Method：A total of 24 males, half with active ALDH2*1/2*1 and the other with inactive ALDH2*1/2*2, was selected through genotyping using restriction fragment length polymorphism. In a double-blind, placebo-controlled cross-over design, each subject consumed 0.5g/kg dose of alcohol, given as a mixture of 40% vodka and orange juice, and placebo(orange juice) on two separate occasions on an average of weekly intervals. The blood alcohol concentrations(BACs) were measured using a breath analyzer at baseline and at 30, 60 minutes after drinking. P300s were measured at baseline and at 30 minutes after alcohol and placebo intake. Vital signs and psychomotor performance[Critical Flicker Fusion Threshold(CFFT), Choice Reaction Time(CRT), Digit Symbol Substitution(DSS)] were measured at baseline and at 60 minutes after alcohol and placebo intake. Subjective responses were measured at the end of the study. The statistical analysis focused on whether there were any differences between groups with different ALDH2 genotypes.

Results：The major results are as follows. 1) BACs in the inactive group were overall equivalent to those in the active group. Only in terms of time, BACs were significantly higher overall at 30 minutes than at 60 minutes after alcohol intake. 2) Pulse rates were significantly increased after alcohol intake compared with placebo, and the increase was greater in the inactive than in the active group. 3) P300 latencies in leads Fz(frontal), Cz(cental) and Pz(parietal) were significantly increased after alcohol intake compared to placebo, and the increase was greater in the inactive than in the active group. P300 amplitudes in leads Cz and Pz were significantly decreased overall after alcohol intake compared to placebo. 4) Compared with placebo, alcohol produced significant effect on the psychomotor performance：impairment in the inactive group, improvement in the active group.5) Compared with placebo, alcohol significantly induced a negative or an intense effect on the subjective responses in the inactive group, but little negative and even a somewhat positive effect in the active group.

Conclusions：These results suggest that ALDH isozyme variance might be an important factor to determine the effects of acute dose of alcohol on the various psychobehavioural functions and also to determine the alcohol use pattern and to predict the future development of alcohol overuse and/or abuse.

Alcohol;ALDH2;P300;Psychomotor performance;Subjective response.

The genetically determined CYP2D6 activity may be considered to be associated with antipsychotic induced extrapyramidal side effects with inter-individual variation. Genetic polymorphism of CYP2D6was determined by polymerase chain reaction(PCR) and MspI restriction fragment length polymorphisms(RFLP) for 194 schizophrenics. Subjects with a 334bp band were classified a1 a1, those with 229bp and 105bp bands a2-a2, and those with all three bands a1 a2. We did not identify schizophrenic subject with poor metabolizer. 194 schizophrenic patients previously treated neuroleptic medication, were assessed by Extrapyramidal Symptom Rating Scale(ESRS).The cases were composed of 33 akathisia, 47 parkinsonism, 21 tardive dyskinesia. These results are similar to the previous understanding that the poor metabolizer is very rare in Orientals compared to Caucasians, therefore, it considered that CYP2D6 genotypes have maybe no association with schizophrenia and extrapyramidal side effects in Koreans.

CYP2D6;Schizophrenia;EPS;Antipsychotics.

This study was designed to evaluate the effects of opioid receptor agonists on the spontaneous alternation behaviour in an animal model of obsessive-compulsive disorder in rats. According to the theory that dopamine is related to the biological etiology of obsessive-compulsive disorder, the effect of the nalbuphine(opioid kappa agonist) and the tramadol(opioid mu agonist), which act as manipulating agents on the inhibition or stimulation of dopamine release, in the spontaneous alternation behaviour were evaluated. 24 hours prior to the experiment, rats were food-deprived. These rats were put into the T-maze, in which white and black goal boxes were baited with small amounts of chocolate milk. Each rat was given 2 set of 7 trials during which it was placed in the start box and allowed to choose the one of the goal boxes for each time. After identifying the stable baseline of spontaneous alternation behaviour, nonselective 5-HT agonist 5-MeODMT(1.25mg/kg/IP) disrupted spontaneous alternation. Rats were stratified into fluoxetine(10mg/kg/IP), nalbuphine(10mg/kg/IP), tramadol(46.4mg/kg/IP), and saline(0.5cc/IP) injec-tion group with experimental drug treatment for 21 days. The effects on the 5-MeODMT(1.25mg/kg/IP) induced disruption of spontaneous alternation behaviour were checked at the next day of discontinuation of drug treatment. The results were as follows； 1) At the day after 21 days of the drug treatment, the nalbuphine treated group and the fluoxetine treated group showed significant difference from the tramadol treated group and the saline treated group in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. 2) Within each drug treatment group, the fluoxetine treated group showed significant difference between before and after the treatment of fluoxetine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. And also, the nalbuphine treated group showed significant difference between before and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. There was no difference between the baseline and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour.

Opioid receptor agonists;Animal model;Spontaneous alternation behaviour.

Schizophrenia has many clinical expressions and probably different etiologic factors. Infections, autoimmune mechanism and related neurodevelopmental abnormalities have been suggested as possible etiologic factors of schizophrenia. It has been reported that immunoreactivity to heat shock proteins, which play a protective role against environmental stresses in a cell, might be related to the pathogenesis of schizophrenia. Therefore, we examined the immunoreactivity to heat shock protein 70kDa and 90kDa (HSP70 and 90) in 91 patients with schizophrenia and 83 normal controls. Ig G antibodies to HSP70 and 90 of sera were quantitated by ELISA. The optical density(OD) was measured by an automated microplate reader at a wavelength of 490nm. The amounts of antibodies to HSPs were expressed as arbitrary units(AU)/ml related to a standard serum. The limit for elevated antibody titers (anti-HSPs positive or negative) was set at two standard deviations added to the mean of the normal controls. Twenty nine(31.9%) of the 91 patients showed anti-HSP70 positive and 19(20.9%) of those showed anti-HSP90 positive. On the other hand, only 1(1.4%) of the normal controls and 4(4.8%) of those showed anti-HSP70 positive and anti-HSP90 positive, respectively. The titers of anti-HSP70 positive were related with BPRS scores, while those of anti-HSP90 positive were not. There were no relationship between antibody titers and clinical variables including age at onset, duration of illness, family history of schizophrenia or number of admission. The titers of anti-HSP70 positive were significantly associated with anti-HSP90 positive. Our results suggest the presence of abnormal immune reactivity involving HSP70 and HSP90 in a subset of patients with schizophrenia.

Schizophrenia;Heat shock protein;Antibody;Autoimmune mechanism.

Objectives：The aims of this study were to discriminate the clinical differences,to measure the estrogen and homovanillic acid levels, to evaluate a correlation between estrogen and homovanillic acid, and to identify an association of cognitivedeficit with estrogen and homovanillic acid among male and female schizophrenics.

Methods：In addition to the structured interviews, the plasma estrogen levels by radioimmunoassay and the homovanillic acid levels by HPLC were measured in 20 male and 21 female schizophrenics as well as 10 healthy male and 9 female controls.

Results：1) The plasma estrogen levels were higher in females than males, andsignificantly higher in female schizophenics than female controls. The homovanillicacid levels were higher in female schizophrenics than female controls, and werelower in male schizophrenics than male controls. 2) The onset age seemed to be earlier in male schizophrenics, and the frequencyof admission, duration of antipsychotic drug administration, dosage of antipsychoticsand duration of illnesses were more in males. The estrogen and homovanillic acid levels were significantly higher in female schizophrenics. 3) The estrogen levels had a significant positive correlation with sex, age and onset age, while the homovanillic acid levels did with sex. However, estrogen were notcorrelated with homovanillic acid levels. 4) The estrogen and homovanillic acid levels were not significantly different betweenmale and female schizophrenics with cognitive deficits. In the schizophrenic patients without cognitive deficits, the estrogen levels were significantly higher in females, while there were no significant sex differences in homovanillic acid.5) In the male and female schizophrenics predominantly with negative symptoms, there were no significant differences in estrogen and homovanillic acid levels. Inthose predominantly with positive symptoms, the estrogen levels were significantlyhigher in females, while there were no sex differences in homovanillic acid levels. 6) In schizophrenics with undifferentiated subtype, the estrogen and homovanillic acid levels were significantly higher in females. In those with paranoid or disorganized subtypes, the estrogen levels were significantly higher in females, while there were no sex differences in the homovanillic acid levels. 7) The mean values of PANSS-negative, PANSS-total, PANSS-CF, MMSE-K and estrogen levels were significantly higher in male schizophrenics with cognitivedeficits. The mean values of illness duration, CGI, PANSS-positive, PANSS-negative, PANSS-total, PANSS-CF and MMSE-K were significantly higher in femaleschizophrenics with cognitive deficits. 8) The variables which showed significant correlation with cognitive deficits werePANSS-negative, PANSS-total, PANSS-CF, MMSE-K and estrogen levels in male schizophrenics. The variables which showed significant correlation with cognitivedeficits were subtypes, onset age, illness durataion, CGI, PANSS-positive, PANSS-negative, PANSS-total, PANMSS-CF and MMSE-K in female schizophrenics.The estrogen levels were significantly correlated with admission frequencies, history of antipsychotic administration, duration of antipsychotic administration and cognitivedeficits in male schizophrenics, while age were not correlated with in females.The homovanillic acid levels had a significant correlation with subtypes and onset age in male schizophrenics, while there were no correlation among variables in females.

Conclusions：Although the plasma concentrations of estrogen and homovanillicacid in female schizophrenics were significantly higher than males, we could not find an association between them. Furtheremore, the various factors affecting on thecognitive deficits, estrogen and homovanillic acid levels seemed to be somewhat different according to sex.

Schizophrenia;Estrogen;Dopamine metabolites;Cognitive deficits;Positive symptoms;Undifferentiated type.

Objectives：The aims of this study were to evaluate changes in plasma superoxide dismutase(SOD) activities in alcohol depedence, to find out variables to influence on the SOD activities, and finally to identify the correlation of SOD activities with the alcohol-associated cognitive disorders.

Methods：For 24 male alcoholics and 21 healthy male controls, plasma SOD activities were measured by spectrophotometry after 1∼2 wks on alcohol withdrawal.Structured interviews and laboratory tests were also performed.

Results：1) Upon comparing SOD activities between controls and alcoholics, the SOD activities were significantly(p<0.01) lower in alcoholics(0.308±0.140 units/mL) than in healthy controls(0.313±0.086 units/mL). 2) Upon comparing SOD activities according to the presence of alcohol-related cognitive disorders, the SOD activities were significantly(p<0.05) lower in alcoholics with cognitive disorders(0.247±0.049 units/mL) than in alcoholics without cognitive disorders(0.317±0.148 units/mL). 3) Upon comparing SOD activities according to the presence of alcoholic polyneuropathy or alcohol withdrawal seizure, the SOD activities showed no significant differences between alcoholics with polyneuropathy or epilepsy and those without.4) Upon analyzing variables influencing on the SOD activities in alcoholics, the SOD activities had the negative correlation with hemoglobin(γ=-0.433) and severity of alcohol withdrawal symptoms(γ=-0.375). 5) Upon comparing variables according to the presence of alcohol-related cognitive disorders, the occurrence of alcoholic polyneuropathy(p<0.05) and blood phosphorus concentrations(p<0.01) were significantly higher in alcoholics with cognitive disorders than those without. 6) Upon analyzing an association between SOD activities and variables in alcoholics with cognitive disorders, the SOD activities were positively correlated with the onset age(γ=0.995), and negatively correlated with the severity of alcohol withdrawal symptoms(γ=-0.996).

Conclusions：Lower SOD activities in alcohol dependence suggested alcohol-associated cognitive disorders and alcohol withdrawal symptoms might be caused by oxidative stress.

Alcohol dependence;Superoxide dismutase activities;Cognitivedisorder;Hemoglobin;Severity of alcohol withdrawal symptoms;Blood phosphorus concentration.

An association of low total cholesterol in blood with psychiatric diseases and suicidal behavior has been suggested. As part of an attempt to further explore this relationship, we examine first, whether serum cholesterol levels in psychiatric patients with suicidal attempt would be lower than in non-suicidal psychiatric inpatients or normal controls, second, whether such significant difference of cholesterol levels would be present when the diagnostic groups are analyzed separately, third, whether low cholesterol level would be associated with a history of serious suicidal attempts, and finally, whether low cholesterol level in suicide attempters is a state or a trait marker. We determined the serum cholesterol levels in 231 patients admitted to an emergency room following an suicidal attempt, in the same numbers of age-, sex- and diagnosis- matched non-suicidal psychiatric controls, and in the same numbers of age-, sex matched normal controls. The seriousness of an attempt was divided into 5 grades according to the degree of the resulting medical injury. Total cholesterol levels in suicide attempters were significantly lower compared with both psychiatric and normal controls, when sex, age, and nutritional status (i.e., body mass index) were controlled for. This significant relationship was observed in major depressive disorders and personality disorders, but not in schizophrenia and bipolar type I disorders. The severity of suicide by a lowering of blood cholesterol was related to the magnitude of the cholesterol reduction. After treatment of their psychiatric ailments, the cholesterol levels in suicide attempters were significantly increased. This result suggests that low cholesterol level in psychiatric patients might be a potential biological marker of suicide risk. It is hypothesized that low cholesterol levels is associated with the suicide by modifying the serotonin metabolism, the production of interleukin-2 and melatonin metabolism in psychiatric patients.

Cholesterol;Depression;Suicide.

Objectives：The purpose of this study was to evaluate the difference of depressive symptoms and attention between estrogen user and non-user in postmenopausal women.

Methods：30 Estrogen users and 30 non-users were participated in this study. They were all menopausal for at least 1 year and have 12 or more education years. We used BDI(Beck depression inventory), digit span and digit symbol to evaluate depressive symptoms and attention in both groups. WWe also measured the plasmaestradiol level and identified the correlation between estradiol level and BDI, digit span and digit symbol.

Results：The demographic data was not different between both groups. Estrogen users scored higher than non-users in digit span(forward) and lower than non-users in BDI. The correlation between estradiol level and BDI, digit span and digit symbol was not significant.

Conclusion：Estrogen replacement therapy was effective in alleviating depressive symptoms but ineffective in improving attention in postmenopausal women.

Postmenopausal women;Estrogen;Depression;Attention.

Objective：Daytime drowsiness or sedation and changes in night sleep are commonly seen in patients treated with clozapine. There is, however, very limited information on their degree and nature during the course of treatment. The purpose of this study was to understand the sleep patterns in chronic schizophrenic patients with clozapine treatment over a period of 24 weeks.

Method：The sleep pattern was evaluated using a set of 5-point scale questionnaire, to record subjective impressions of the night sleep induction, maintenance and quality, and daytime drowsiness and fatigue. In addition, unusual experiences associated with night sleep were recorded. The sleep questionnaire was repeatedly administered at baseline and at 1, 2, 4, 8, 12 and 24 weeks of drug treatment. At present, data on 12 patients has been collected.

Results：All the components of night sleep were significantly improved in the 1st through the 12th week after treatment with clozapine. Daytime drowsiness was significantly higher in the 1st to the 2nd week after the treatment and fatigue was also significantly higher in the 1st to the 4th week after the treatment. Eight patients experienced noticeable increases in salivation during night sleep, and of these, one also reported frequent nocturnal urination and even enuresis. However, all these adverse factors did not affect the major sleep patterns.

Conclusions：These findings suggest that the beneficial effects of clozapine on night sleep might last much longer than the undesirable effect of daytime drowsiness and fatigue. In other words, tolerance of the hypnotic action of clozapine might develop late and tolerance of the daytime drowsiness and fatigue might be evident earlier.

Clozapine;Chronic schizophrenia;Sleep.

The fluoxetine is one of the most frequently prescribed drugs for the treatment of depression and obsessive-compulsive disorder(OCD). This has been known as one of the most safest medication. But since the advent of this drug, there have been several reports of side effects-the mania and suicidal ideation-encountered during coadministration of fluoxetine with or without other psychotropic drugs. We experienced a case of 20 years old male OCD patient who developed into abrupt manic state and also was preoccupied with intense suicidal ideation following fluoxetine use. He was a only child in his family and his father had a history of alcoholism about 15years ago. Our patient's obsessive-compulsive symptoms have been occured since puberty. His OCD symptoms and anxiety were aggravated since joining the army. Beside these facts, we could not find any other psychiatric history such as depressive disoder and bipolar disorder. We used the fluoxetine starting dosage of 20mg and increased to 40mg at second week. About 3 weeks after the treatment, he developed sudden manic symptom and more aggravated suicidal ideation without any OCD symptoms. He felt vitalized and energetic without having enough sleep and food. These symptoms were ceased over two weeks by stopping medication. Up to this point, the reason why fluoxetine induces mania and suicidal preoccupation is unclear. But somehow the fluoxetine has effects on serotonin receptor and serotonin-dopamine regulations, thus we could make an assumption that fluoxetine can induce mania, extrapyramidal symptoms(EPS) and suicidal ideation in some part of the serotonin unbalanced patients.We think this would be the first report to remark on fluoxetine's suicidal and manic side effects in Korea. So here we present the case with the summary of reviewed articles.

Fluoxetine;Mania;Suicide.

Nefazodone, a newer antidepressant is a phenylpiperazine derivative that inhibits the reuptake of both norepinephrine and serotonin, and antagonizes 5-HT_2A and a1 adrenergic receptors. Compared with SSRIs, nefazodone caused the fewer activating symptoms, adverse gastrointestinal effects(nausea, diarrhea, anorexia) and adverse effects of sexual function, but is associate d with the more dizziness, dry mouth, constipation, visual disturbances and confusion. We report on 4 cases of visual disturbances and hallucinations in patients taking nefazodone. It is not certain what mechanisms mediated these side effects, but three mechanisms are possible. 1) Nefazodone, as a 5-HT₂ antagonist, might induce visual disturbances. 2) mCPP, metabolite of nefazodone might contribute to the hallucination through action on 5-HT receptor. 3) Dopaminergic enhancing activity of nefazodone might cause hallucination. These case report raises the possibility that dose-related perceptual disturbances may exist with nefazodone. The fact emphasizes the need to pay close attention to all possible drug interactions, particularly in patients treated with multiple psychoactive agents, older patients, and patients with decreased hepatic function.

Nefazodone;Adverse effect;Visual disturbance;Hallucination.

Object：This study was designed to evaluate the effects of olanzapine on the schedule- induced polydipsia(SIP) which is one of animal model of obsessive-compulsive disorder in rats. We administered olanzapine as a serotonin and dopamine blocking agent, fluoxetine as a selective serotonin reuptake inhibitor, and haloperidol for the dopamine antagonist to rats which showed schedule-induced polydipsic behavior.

Methods：Spraque-Dawley rats weighing 200-250gm were individually housed and maintained and allowed free access to water. The rats were placed on a restricted diet. To induce polydipsia, rats were placed in the cage where a pellet dispenser automatically dispensed 90mg pellets on a fixed-time 60 seconds(FT-60s) feeding schedule over 150 minute test session per day. Water was available at all times in the cage. After 4 weeks of daily exposure to the FT 60s feeding schedule, experimental rats met a predetermined criterion for polydipsic behavior (greater than 3 times of water per session on average). 5 groups of rats were administered olanzapine (3mg/kg, i.p), olanzapine(10mg/kg, i.p), fluoxetine (5mg/kg, i.p.), haloperidol (0.1mg/kg, i.p.), and vehicle (1cc/kg, i.p.) for 3 weeks. The rats were tested once a week to access schedule induced polydipsic behavior. Water bottles were weighed before and after the 150-minute test session. The chronic effects of administration of experimental drugs on schedule induced polydipsic behavior were analyzed with ANOVA and Scheffe test as a post-hoc comparison. In order to measure water consumption in non-polydipsic food-deprived rats, a separate group of rats (N=8) were individually housed and given a single bolus (14.5gm) of food per day which maintained them at their average body weight.

Results and Conclusion：The results were as follows；1) After 4 weeks of scheduled feeding procedure, the experimental group showed significant differences than the bolus control in the amount of water consumption as compared with their average water intakes for 4 weeks. At the same periods, there were no differences between the experimental group and the bolus control in the body weight. 2) The fluoxetine group showed significant decrease in the amount of water intake over the 3 weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 3mg group showed significant decrease in the amount of water intake at 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 10mg group showed significant decrease in the amount of water intake at 2nd and 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. However, the haloperidol group and the vehicle control group showed no changes of amounts of water intake for 3 weeks of treatment as compared with their average amount of polydipsic water intakes. 3) The fluoxetine group showed significantly lower amounts of water intake than the haloperidol group at 2nd weeks of drug treatment. And also the fluoxetine group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. The olanzapine 3mg group and the olanzapine 10mg group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. Above findings suggest that the fixed time feeding procedure for schedule-induced polydipsia as an animal model of obsessive compulsive disorder was effective to the evaluation of pharmacological challenge study. The authors assume that the serotonin hypothesis and the serotonin-dopamine interaction hypothesis are preferred to the dopamine hypothesis in the biological etiology of obsessive-compulsive disorder.

Olanzapine;Animal model of obsessive-compulsive disorder;Schedule-induced polydipsia.

The neurophysiological study has been widely used in search of the relationship between brain and behavior. The basic techniques for the animal experiments of this kind such as stereotaxic techniques, lesioning methods, the methods of electrical stimulation and recording, and confirmation of histological location were briefly reviewed. Nevertheless, the importance of complementary neurochemical, neuroanatomical and behavioral studies can not be neglected.

Stereotaxic techniques;Lesioning;Electrical stimulation;Electrical recording;Histology;Behavioral tests.

Advances in molecular biology contribute to the understanding genetic mechanism of psychiatric disorders. They have renewed hope for the discovery of disease relevant gene. However, the results somewhat confused. And we will wait for a long time for the application of gene therapy in schizophreniar. Fortunately we could classified the schizophrenia with genotypes of dopamine and serotonin receptors. It is expected that this genetic classification could provide key strategy for the therapeutic application in biological treatment for schizophrenia. The purpose of this article is to call attention of the institute participants to linkage, association, mRNA expression, genotypic classification and to the need for more systemic research. The author summarized the modified methods which were done in his laboratory in appendix.

Schizophrenia;Linkage;Association;mRNA expression;Genotypic classification;Therapeutic application.

We provide the reader with a brief introduction to the neurobiology of neuropeptides. Several comprehensive reviews of the distribution and neurochemical, neurophysiological, neuropharmacological and behavioral effects of the major neuropeptides have recently appeared. In reviews of the large number of neuropeptides in brain and their occurance in brain regions thought to be involved in the pathogenesis of major psychiatric disorders, investigators have sought to determine whether alternations in neuropeptide systems are associated with schizophrenia, mood disorders, anxiety disorders, alcoholism and neurodegenerative disease. There is no longer any doubt that neuropeptide-containing neurons are altered in several neuropsychiatric disorders. One of the factors that has hindered neuropeptide research to a considerable extent is the lack of pharmacological agents that specifically alter the synaptic availability of neuropeptides. With the exception of naloxone and naltrexone, the opiate-receptor antagonists, there are few available neuropeptide-receptor antagonists. Two independent classes of neuropeptide-receptor antagonists has been expected to be clinically useful. Naltrexone, a potent μ-receptor antagonist, has been used successfully to reduce the need for alcohol consumption. And cholecycstokinin antagonists are now in development as a new class of anxiolytics, which would be expected to be free from tolerance and physical dependence and lack of sedation. In this review, we deal with these two kinds of neuropeptide system, the opioid system and cholesystokinins in the brain. The role of opioid systems in the reinforcement after alcohol consumtion and that of cholesystokinins in the pathogenesis of anxiety will be discussed briefly. As we know, the future for neuropeptides in psychiatry remains bright indeed.

Neuropeptide;Naltrexone;Alcoholism;Cholecystokinin;Panic.

Any compound which disrupts the integrity of psychological aspects of performance, in particular, cognitive ability and psychomotor function analogous to the psychological behaviors of routine life, is known to be behaviorally toxic. A significant level of behavioral toxicity will interfere with patient safety and quality of life, and also may be counter-therapeutic by exacerbating the condition that the drug was prescribed for. Now, behavioral toxicity of psychotropic drugs has become one of the main growth areas of psychopharmacological research. Evaluation of the potential of drug-induced behavioral toxicity is important not only to the experimental researcher involved in human psychopharmacology, but also to the clinical practitioner treating psychiatric patients. This article attempts to describe behavioral toxicity of the three classes of psychotropic drugs - benzodiazepines, antidepressants and neuroleptics. After a brief discussion of some methodological issues arising in the investigation of behavioral toxicity, each of these drug classes is reviewed in the context of practical importance rather than purely scientific concern. The last session summarizes some suggestions for future studies on drug-induced behavioral toxicity.

Behavioral toxicity;Psychotropic drugs.

Clinicians can use therapeutic drug monitoring(TDM) to optimise dosage decisions with psychotropic drugs, in order to maximize efficacy and prevent toxicity, especially when individuals are nonresponsive to treatment or vulnerable to adverse reactions with standard doses because age, disease states or drug interactions. Currently, therapeutic drug concentrations have been established for the TCA and lithium. There is also evidence for the usefulness of TDM with carbamazepine, valproic acid and some antipsychotic drugs. However for most psychotropic drugs this approach remains experimental. TDM-assisted psychiatric treatment is potentially useful and cost effective, particularly when applied by psychiatrists who are knowledgeable of pharmacokinetics and pharmacodynamics.

Therapeutic drug monitoring(TDM);Psychotropic drug;Drug concentration.

Apoptosis is a form of cell death in which the cells shrink and exhibit nuclear chromatin condensation and DNA fragmentation, and yet maintain membrane integrity. Many lines of evidence have shown that brain neurons are vulnerable to degeneration by apoptosis. Also it has been suggested that apoptosis is one of the mechanism contributing neuronal loss in Alzheimer’s disease(AD), since the conditions in the disease(Aβ peptide, oxidative stress, low energy metabolism) are the inducers that activate apoptosis. Indeed some neurons in vulnerable regions of the AD brain show DNA damage, chromatin condensation, and apoptic bodies. Consistently, mutations in AD causative genes(Amyloid precursor protein, Presenilin-1 and Presenilin-2) increase Aβ peptide_1-42(Aβ_1-42) and sensitize neuronal cell to apoposis. However, several lines of evidence have shown that the location of neuronal loss and Aβ peptide deposition is not correlated in AD brain and transgenic mice brain over-expressing Aβ_1-42. Taken together, these data may indicated that Aβ peptide(and other causative factors of AD) can interact with other cellular insults or risk factors to exacerbate pathological mechansim of AD through apoptosis. Thus, this review discusses possible role and mechanism of apoptosis in AD.

Apoptosis;Alzheimer’s disease;β-Amyloid protein;Amyloid precursor protein;Presenilin 1;Presenilin 2.

The neuropsychiatric sequelae of traumatic brain injury are effects on complex aspect of cognition, emotion and behavior. They include problems with attention and arousal, concentration, executive function, intellectual changes, memory inpairments, personality changes, affective disorders, anxiety disorders, psychosis, apathy, aggression, and irritability. There are many useful therapeutic approaches available for people who have been brain injuries. Although a multifactioral, multidisciplinary, collaborative approach to treatment is proposed, for purposes of exposition the author have divided treatment into psychopharmacological, cognitive, behavioral, psychological, and social interventions.

Traumatic brain injury;Psychopharmacological treatment;Cognitive treatment;Behavioral treatment;Psychological intervention.

Objectives：Phencyclidine(PCP) or PCP-like substances such as ketamine have been known to rekindle the cognitive dysfunction in schizophrenia. The aims of this study were to identify whether PCP-like substances can produce cognitive deficit in schizophrenia, to discuss relation with aging process, and finally to speculate underlying neurochemical mecha-nisms by various drug responses.

Methods：In experiment I, radial maze tests were done in 24 Sprague-Dawley rats for 3 days to get baseline data. Being divided into 4 groups(6 rats respectively) of normal aged, normal adult controls, atropine-treated and ketamine-treated, the radial maze tests were repeated on every week for 6 weeks, and then the rats were sacrificed by intracardiac perfusion with phosphate-buffered 10% formaldehyde solution for histology. The brain specimen was stained with hematoxylin-eosin to count cells in the prefrontal cortex and hippocampus. In experiment II, radial maze tests were done for 48 rats before any drug treatment and only after ketamine administration. Thereafter, haloperidol, bromocriptine, clonidine, nimodipine, tacrine, valproic acid, naloxone and fluoxetine were intramuscularly injected on every other day in addition to ketamine. Radial maze tests were repeated on every week for 6 weeks, and then rats were prepared by the same procedure for histology.

Results：1) Reaction times of radial maze tests of atropine-treated rats were significantly prolonged than those of normal aged(p<0.05) or normal adult controls(p<0.05). Cell numbers of prefrontal cortex & hippocampus in ketamine-treated rats were significantly reduced than those in normal aged(p<0.05) or normal adult controls(p<0.005). 2) Reduced cell numbers by ketamine became significantly raised by tacrine administration in prefrontal cortex & hippocampus(p<0.05), while there were no significant changes on radial maze tests. Cell numbers also tended to be raised by nimodipine, fluoxetine and haloperidol administration.

Conclusions：In conclusion, the visuospatial memory disorders in ketamine-induced psychotic rats might be partly asso-ciated with aging process. Furthermore, the responses to the various drugs suggested cholinergic system might have an important role in the neurochemical mechanism of the cognitive dysfunction in ketamine-induced psychosis. Otherwise, calcium metabolism as well as serotonergic and dopaminergic systems seemed to be possibly related.

Ketamine;Visuospatial memory disorders;Aging;Radial maze tests;Prefrontal cortex;Acetylcholine.

The changes of electroencephalogram(EEG) in patients with dementia of Alzheimer’s type are most commonly studied by analyzing power or magnitude in traditionally defined frequency bands. However because of the absence of an identified metric which quantifies the complex amount of information, there are many limitations in using such a linear method. According to the chaos theory, irregular signals of EEG can be also resulted from low dimensional deterministic chaos. Chaotic nonlinear dynamics in the EEG can be studied by calculating the largest Lyapunov exponent(L₁). The authors have analyzed EEG epochs from three patients with dementia of Alzheimer’s type and three matched control subjects. The largest L₁ is calculated from EEG epochs consisting of 16,384 data points per channel in 15 channels. The results showed that patients with dementia of Alzheimer’s type had significantly lower L₁ than non-demented controls on 8 channels. Topographic analysis showed that the L₁ were significantly lower in patients with Alzheimer’s disease on all the frontal, temporal, central, and occipital head regions. These results show that brains of patients with dementia of Alzheimer’s type have a decreased chaotic quality of electrophysiological behavior. We conclude that the nonlinear analysis such as calculating the L₁ can be a promising tool for detecting relative changes in the complexity of brain dynamics.

Dementia of Alzheimer’s type;Chaos;Nonlinear;Dynamic;EEG;Lyapunov exponent.

Objectives：To evaluate the relation of familial history of alcoholism and plasma level of β-endorphin, ethanol, β-endorphin, cortisol and blood glucose were compared in 48 male alcoholics and 29 normal controls.

Methods：Subjects are divided into two groups by family history of alcoholism. Blood samples were obtained before and after 0.75mg/kg of ethanol consumption at 7th admission day.

Results：1) The ratio of family history positive to negative of the patient group was 2 to 1.2) The age at admission of positive family history group was younger than negative group.3) There was no significant difference in change of plasma ethanol level among three groups.4) There was no significant difference in change of plasma β-endorphin level among three groups.5) There was no significant difference in change of plasma cortisol level among three groups.6) There was no significant difference in change of fasting blood sugar level between two patient groups.

Alcoholism;Family history;β-Endorphin.

Objectives：To evaluate the relation of onset-age and plasma level of β-endorphin, Ethanol, β-endorphin, cortisol and blood glucose were compared in 48 male alcoholics and 29 normal controls

Methods：Alcoholics are divided into two groups by onset-age of alcoholism. Blood samples were obtained before and after 0.75gm/kg of ethanol consumption at the 7th admission day.

Results：1) The ratio of onset-age before 25 years to after 25 years of the patient group was 2 to 3. 2) There was no significant difference in age at admission between two patient groups. 3) There was no significant difference in change of plasma ethanol levels among three groups. 4) There was no significant difference in change of plasma β-endorphin levels among three groups. 5) There was no significant difference in change of plasma cortisol level among three groups. 6) There was no significant difference in change of fasting blood sugar level among two patient groups.

Alcoholism;Onset-age;β-Endorphin.

Bethanechol, a cholinergic agonist, has been recommended for the management of peripheral anticholinergic side effects during the treatment of antipsychotic medications. But there have been few studies which have evaluated the drug interactions of antipsychotics and bethanechol, even the treatment effects of bethanechol on anticholinergic side effects. So the authors have evaluated whether psychopathology and plasma haloperidol and reduced haloperidol concentrations are significantly changed or not when bethanechol was administrated with maintained doses of haloperidol and other coadministrated drugs(such a benztropine). Also we have evaluated the abating effects of bethanechol on anticholinergic side effects during the treatment with haloperidol. Fifteen schizophrenics with higher than 5 of total score of anticholinergic side effects of ‘Rating scale for side effect’ were assigned to two groups, and bethanechol 30mg/day and 60mg/day were applied on each group for 4 weeks. The daily haloperidol dosages were fixed before 2 weeks of study. We assessed anticholinergic side effects by’ Rating scale for side effect’ and psychopathology by BPRS, and plasma haloperidol and reduced haloperidol concentrations by HPLC at baseline, 2nd week and 4th week. The results were as followed, 1) there was no significant change of plasma haloperidol and reduced haloperidol concentration, 2) at baseline, the dosage of haloperidol showed significant correlation with the total score of anticholinergic side effect, but not at 2nd week and 4th week, 3) in 60mg/day group, dry mouth and the total score of anticholinergic side effects were significantly improved, but not in 30mg/day group, 4) there was no significant change of BPRS except withdrawal at 2nd week. These results suggest that coadministration of bethanechol influenced neither on psychopathology nor on plasma haloperidol and reduced haloperidol concentrations and that improved dry mouth and total score of anticholinergic side effects at 60mg/day.

Schizophrenia;Anticholinergic side effects;Haloperidol;Plasma haloperidol and Reduced haloperidol concentrations.

Objective：This study was a open clinical trial aimed at exploring the effectiveness of combined treatment with estrogen and antipsychotics to the chronic female schizophrenics.

Method：40 female patients who met DSM-Ⅵ criteria for schizophrenia who were chronically ill were randomly assigned to estrogen group(EG) and control group(CG). EG patients were received estrogen 1.25mg for 8weeks in addition to their routine antipsychotic regimens. CG patients were received their routine antipsychotic regimens only. Both groups were evaluated by PANSS(Postive and Negative Syndrome Scale), CGI(Clinical Global Impression) at 0, 4, 8 week during the trial period and compaired with each other.

Results：40 female patients have completed the study during 8weeks. EG was significantly improved in PANSS and CGI scores than CG during the 8weeks. In EG patients, all symptom subtypes(positive symptoms, negative symptoms, general psychopathology symptoms) of PANSS were significantly improved and positive symptoms were most significantly improved at 8week.

Conclusions：This results support the clinical value of combined estrogen therapy among chronic female schizophrenics.

Estrogen;Schizophrenia;Combined treatment.

Objective：Base on clinical practice, the authors report a case of tardive dyskinesia arising during the course of treatment with resperidal.

Methods：This article was review and analysis of a case on risperidone-induced tardive dyskinea.

Results：Mrs K, a 51-year-old woman with a 1-year history of schizophrenic disorder, gradually developed tardive dyskinetic movement of the mouth, lip, and tongue over a 4 month period(From July, 1996 to June, 1997) while taking risperidone. Initially she was treated with haloperidol and alprazolam. However, the haloperidol was subsequently discontinued because of EPS developed.From 11th March, 1997, she was observed to have a severe form of tardive dyskinesia involving her tongue, lip, and mouth. After risperidone was withdrawn at 9th May 1997, her tardive dyskinetic movement was disappeared.

Conclusions：This is, to our knowledge, the first report of the onset of tardive dyskinesia in a patient taking risperidone. However, additional controlled studies of specific questions are needed；e.g., the dose-response curves for produce tardive dyskinesia and the mechanism of producing risperidone-induced tardive dyskinea and so on.

Risperidone;Tardive dyskinesia.

Authors report a case of separation anxiety disorder, which developed as a side effect during haloperidol treatment of Tourette syndrome(TS). In this case, 14 years old boy developed attention deficit symptoms during his infancy. At 4th grade of primary school, he developed vocal tic, motor tic, and coprolalia. With 5mg/day of haloperidol treatment his symptoms of TS were subsided. During the treatment, he developed features of separation anxiety disorder, including dependence, pleading, clinging, and sadness. Symptoms of attention deficit and separation anxiety disorder were improved by 25mg/day of imipramine treatment. During haloperidol treatment of TS, careful observation may be needed whether separation anxiety disorder-like symptom develops.

Tourette syndrome;Separation anxiety disorder;Haloperidol;Imipramine.

Neuroleptic malignant syndrome(NMS) is an uncommon but potentially fatal idiosyncratic reaction to neuroleptics, characterized by muscular rigidity, fever, autonomic dysfunction, and altered consciousness. The major theories to explain NMS is central dopaminergic blockade, but it is unclear. Risperidone is a new antipsychotic drug, a benzisoxazole derivative that blocks dopamine D₂ receptor and serotonin type 2 receptor. The comparatively greater serotonin-blocking activity is believed to give risperidone the specific property of not causing any more extrapyramidal side effects than conventional antipsychotics at the optimal dose of 4-8mg/day. It is postulated that risperidone is unlikely to cause NMS. Here, we report a case of risperidone induced neuroleptic malignant syndrome.

Risperidone;Neuroleptic malignant syndrome.

Antipsychotic drugs(APDs) have been effective to alleviate psychotic symptoms of schizophrenia. However, some schizophrenic patients do not respond to APDs. In addition to psychotic symptoms of schizophrenia, negative symptoms, excitement, violence, agitation, depression, and disorganization are frequently noted in patients with schizophrenia. Though APDs are the first line drugs for these symptoms, other drugs than APDs to augment the effects of APDs are efficacious for the treatment of these symptoms. Such augmenting drugs include benzodiazepines, anticonvulsants, antidepressants, lithium, and electroconvulsive therapy. These augmentation strategies can boost the effects of APDs or decrease the requirements of APDs, and consequently decrease the chance of the occurrence of side effects of APDs. Augmenting strategies are revewed for each class of drugs or treatment modality.

Schizophrenia;Antipsychotic drugs;Augmentaion.

Mood disorder is a medical illness resulting from the disorder of CNS neurotransmission and its principal therapeutic tool is pharmacotherapy. Psychotherapeutic drugs for mood disorder have some clinical limitations which are due to no or partial response, decreased compliance for drug by the side effects, and delayed therapeutic effects. So, general hope of all clinicians that mood diorder will respond to a single psychotherapeutic agent may be the exception rather than the rule. Recently, combined drug treatments have become increasingly popular to overcome the clinical limitations of individual agent in mood disorder. Combined treatments are usually used for augmenting or initiating rapidly the effect of drug, and for treating different target symptoms or drug side effects. When combined treatments being tried, knowledge of the action mechanism, pharmacokinetics, and pharmacodynamics is crucial to cope with the possible adverse reactions of drugs.

Mood disorder;Combined drug treatment;Augmentation.

The serotonin reuptake inhibitors(SRIs) and the serotonin selective reuptake inhibitors(SSRIs) are considered the first choice agents for pharmacologic treatment of obsessive-compulsive disordr(OCD). However, many patients with OCD experience little or no improvement in their symptoms when treated with SRIs or SSRIs. Patients who have experienced a partial or no response to an SRI/SSRI at 10 to 12 weeks are often considered for augmentation strategies. Nearly every class of psychotropic medications has been tried in an open fashion, though augmentation strategies have been somewhat disappointing.

OCD;Augmentation.

While the therapeutic efficacy of antipsychotic drugs is not in doubt, a variety of undesirable side effects are common. They can be a disincentive to good compliance with treatment, resulting in increased possibilities for relapse and hospitalization. They can be distressing and disabling and thus interfering with patient safety and quality of life. Furthermore, they may be counter-therapeutic by exacerbating the condition that the drug was prescribed for. In this article, we will provide an overview of management of antipsychotic- induced side effects, with a particular emphasis on the most common side effects as well as less common but serious side effects. In addition, some practical issues regarding the management of side effects will be discussed.

Antipsychotic drugs;Side effects;Treatment strategy.

To consider current concepts of epilepsy further, the brief review begins with a discussion of what is epilepsy, discribes multifactorial nature of epileptic disorders, and ends with a presentation of current classifications. A combination of the standard antiepielptic drugs(AEDs)may be necessary to treat intractable seizures, but no studies have been done to indicate an optimal combination. The new AEDs provide alternative choices, but questions remain about the optimal timing and manner of administration. AEDs selection must individualized, no drug of choice can be named for all patients.

Current concepts of epilepsy;New AEDs.

With a rapid development of neuroscience, the theories related to the pathophysiology of schizophrenia have been changed a lot from a simple hyperdopaminergic one to the various complicated ones. Among these, the theories regarding prefrontal cortex(PFC) pathology as a cause of schizophrenia are gaining more recognition as the results of neuroimaging and neuropsychological tests in schizophrenia consistently report abnormalities in PFC. Therefore, we first reviewed the unique characteristics of PFC in anatomy, neurochemistry and neurophysiology to enhance an understanding of those ones. Secondly, various neurotransmitter, neurodevelopmental and neural network theories of schizophrenia introduced recently were reviewed in terms of PFC pathology.

Prefrontal cortex;Schizophrenia;Dopamine.

In mordern society, nutritional and appetite disorders occur in epidemic proportions and are serious health harzards. Obesity and diabetes affect over 30% of American population, while eating disorders, such as anorexia nervosa and bulimia nervosa occur in a growing number of adolescences and young adults. The changes in various sociocultural aspects with the introduction of Westernized culture have had the effect of increasing the risk of same problems in Korea. Disorderd eating patterns are a primary symptom of numerous psychiatric disorders and loss of appetite and cachexia, during illness or in the elderly, preclude proper medical treatment for restoring good health or preserving life. Increased understanding of the systems of the body and brain, related to energy and nutrient balance, may help us to treatment and ultimately prevent these commom disorders. In this review, the author highlights the psychobiological mechanisms or factors which are associated with eating behavior, especially in the view of intake psychobiology. This review would be concentrated on 1) the theoretical concepts and theories of eating behavior；2) the psychobiological determinants of food intake；and 3) the psychobiological control of eating behavior.

Psychobiology;Eating behavior;Food intake.

An association study with Korean schizophrenic patients(N＝84) and normal controls(N＝87) was performed to find the relationship between catechol-Ο-methyltransferase(COMT) gene polymorphism and schizophrenia using polymerase chain reaction-restriction fragment length polymorphism. When we compared the allele and genotype frequencies of BglI COMT gene polymorphism in schizophrenics and normal controls, there was no significant difference between two groups. Our results do not support an association between the BglI polymorphism of COMT gene and schizophrenia.

Schizophrenia;Association;COMT;Polymorphism;Alleles.

The 5-HT_2A receptor is of great interest for research into schizophrenia and psychopharmacology in light of the observation that schizophrenic patients has 5-HT cortical-subcortical imbalance and atypical antipsychotic clozpine has 5-HT_2A antagonists properties. An significant association between schizophrenia and the T102C polymorphism of the gene for 5-HT_2A receptor has been reported. In this study, we investigated an association between schizophrenia and the T102C polymorphism of the gene for 5-HT_2A receptor in Korean schizophrenic patients. The subjects consisted of 139 schizophrenic patients and 88 normal controls. Genomic DNA was amplified by PCR and digested with MsPI. The uncutt product identified allele 1(nucleotide sequence TCT)；digested products of 216bp and 156bp identified allele 2(nucleotide sequence TCC). The allele frequencies and the genotypic distribution of 5-HT_2A receptor gene were not significantly different between schizophrenic patients and normal controls. Since allele frequencies of the T102C polymorphism may differ between individuals of different ethnic backgrounds, it needs to be conducted in an advanced research.

5-HT_2A;T102C polymorphism;Schizophrenia.

Cytosine arabinoside(AraC) inhibits DNA synthesis and β-DNA polymerase, an enzyme involved in DNA repair. This, a potent antimitotic agent, is clinically used as an anticancer drug with side effect of severe neurotoxicity. Earlier reports suggested that inhibition of neuronal survival by AraC in sympathetic neuron may be due to the inhibition of a 2'-deoxycytidine-dependent process that is independent of DNA synthesis or repair and AraC induced a signal that is triggers a cascade of new mRNA and protein synthesis, leading to apoptotic cell death in cultured cerebellar granule cells. The present study would suggest whether caspase family(ICE/CED-3-like protease) involved in AraC-induced apoptosis pathway of PC12 cells. It was observed that treatment of PC12 cells with AraC led to decrease of viability by MTT assay and morphology changes, which did not suggest that AraC induced apoptosis in PC12 cells. The mRNA of caspase-1/caspase-3 were expressed in PC12 cells constitutively, and AraC did not activate caspase family. These results suggest that caspase-1/caspase-3 may not be required for AraC-induced cell death pathway in PC12 cells.

Cytosine arabinose;PC12 cell;Apoptosis.

Objective：Many evidences suggest that patients with bipolar disorder have functional abnormalities in their postreceptor signal transduction pathways, and mood stabilizing effect of lithium is exerted by modulating this dysfunctioning system. Carbamazepine, an antiepileptic agent, is also known to be effective in the treatment and prevention of bipolar disorder. But the precise mechanism of action of the drug is still poorly understood. This study was performed to elucidate the possible therapeutic mechanism of carbamazepine.

Method：The effects of chronic carbamazepine administration on protein kinase A and protein kinase C activities in frontal cortex of rat brain after 2 weeks of drug administration were measured and compared with those of control subjects.

Results：Mean(±SE) value of activity(phosphate transfer μmol/mg of protein·min) of protein kinase A in control and test group was 0.249563±0.036 and 0.539853±0.078, and that of protein kinase C was 0.654817±0.053 and 1.146205±0.052 respectively, being increased in test group. And differences between the two groups were statistically significant for both enzymes(protein kinase A；p<0.01, protein kinase C；p<0.001).

Conclusion：These results show that chronic carbamazepine administration increases protein kinase A and C activities, and concerning the possible mode of therapeutic action in bipolar disorder it is suggested that enhanced enzymes phosphorylate receptor-G-protein-effector complexes to dampen hyperfunctioning neuronal activity and thus stabilize the system.

Carbamazepine;Protein kinase A;Protein kinase C;Second messenger system.

Objectives：Alcohol-induced oxidative stress has been known to injure various tissues or organs. This stress is related with free radicals which are produced as the result of long-term alcohol consumption. Malonyldialdehyde(MDA) is produced by the interaction of free radicals and cell membrane lipids, and indicates the degree of lipid peroxidation indirectly. The purpose of this study was to investigate the relationship between red blood cell(RBC) membrane lipid peroxidation by free radicals, and associated hepatic injuries and hematologic changes.

Methods：Thirty-three subjects diagnosed as alcohol dependence according to DSM-IV diagnostic criteria were evaluated within 72 hours after discontinuing alcohol drinking. Clinical characteristics were evaluated by CAGE questionnaire and Korean Michigan Alcoholism Screening Test(MAST). RBC membrane MDA level was measured as the marker of RBC membrane lipid peroxidation. Aspartate aminotransferase(AST), alanine aminotransferase(ALT) and gamma-glutamyltransferase(GGT) were used as the biochemical markers of liver damage due to alcohol ingestion. The alcohol-induced hematologic change was assessed by mean corpuscular volume(MCV).

Results：The results were as follows. Clinical characteristics were not different between two groups having normal and abnormal levels of AST, ALT, GGT or MCV. The levels of MDA were not correlated with the clinical characteristics and serum levels of AST, ALT and GGT. However, there was a significant correlation between the levels of MDA and the value of MCV(p＝0.017).

Conclusions：These findings suggest that oxidative stress in alcohol dependence may not be reflected in liver enzyme markers such as AST, ALT and GGT, but may be reflected in MCV.

Alcohol dependence;Oxidative stress;Mean corpuscular volume;Aspartate aminotransferase;Alanine aminotransferase;Gamma-glutamyltransferase.

The authors tried to confirm the significant changes of plasma homovanillic acid(HVA) concentration after insulin administration in comparison with those of usual diurnal variation in the same subjects. Male patients with schizophrenia taking neuroleptics were participated in a study of diurnal variation and insulin induced dopaminergic perturbation, with multiple samplings at baseline, 30minutes, 60minutes and 90minutes after insulin administration(n＝18). Ten patients were sampled at baseline and 60minutes after insulin administration. There was a diurnal variation of plasma HVA concentrations, which decreased gradually from 8 am to 9：30 am. We confirmed that regular insulin(0.1 unit/kg) blocked the normal diurnal variations and increased plasma HVA concentrations. This pattern was not correlated with clinical variables, such as age, onset age, duration of illness and presence of family history. Schizophrenic patients were grouped by the positive and negative syndrome scale. In contrast to our previous study, the concentrations of positive and negative groups were similar at baseline. The HVA concentrations of negative group after insulin administration were higher than those of positive group without statistical significance. We have a plan to modify the current insulin-HVA method. In the near future, we will try to confirm whether the modified insulin-HVA method can be used as a biological indicator for the elucidation of complex clinical manifestations of schizophrenia.

Schizophrenia;Insulin;Homovanillic acid.

Object：This study was performed in order to examine the correlation between acute neuroleptic-induced dystonic reactions and serum iron level.

Method：Serum iron levels were measured in psychiatric inpatients who had developed acute neuroleptic-induced dystonia(N＝41) and in control patients with no history of acute dystonic reactions(N＝37). Serum iron levels were compared in acute dystonic inpatients before starting treatment with neuroleptics and after acute dystonic reaction.

Results：The patients exhibiting acute dystonic reactions had significantly lower serum iron levels than the patients without acute dystonic reactions.

Conclusion：This result supports an association between low serum iron and the occurrence of neuroleptic-induced acute dystonic reactions.

Serum iron;Acute dystonic reactions;Antipsychotic drug.

Objectives：Risperidone, an atypical antipsychitics which blocks both dopaminergic and serotonergic receptors, have a good response to the negative symptoms as well as positive symptoms, and improve cognitive dysfunction of schizophrenic patients. Furthermore, it has few extrapyramidal side effects and tardive dyskinesia. Although it had been reported that the atypical antipsychotics have less effect on prolactin(PRL) than the classical antipsychotics, we could experience PRL-associated symptoms such as amenorrhea, galactorrhea and hyperprolactinemia in practice. Therefore, we tried to identify the sex differences of risperidone-induced hyperprolactinemia, to evaluate factors affecting PRL levels, and to know the association between cognitive disorders and PRL.

Methods：The baseline levels of PRL and TSH prior to risperidone administration were measured by enzyme immunoassay method for 50 patients(25 males and 25 females) admitted with schizophrenia, schizoaffective disorder or schizophreniform disorder according to the DSM-IV classification, and the measurements of PRL were repeated on the 2nd and the 4th wks of risperidone administration. Concomitantly, the severity of psychotic symptoms using CGI, BPRS and PANSS, and the cognitive dysfunction using PANSS-CF were assessed prior to, on the 2nd and the 4th wks of risperidone administration. The PRL and TSH levels of 54 healthy controls(29 males and 25 females) who had no medical, neurological and psychiatric illnesses were also evaluated. Furthermore, the correlation with the psychiatric diagnosis, education, age, sex, duration of illnesses, risperidone dosage, duration of risperdone administration, TSH concentration, cognitive function, severity of psychotic symptoms were also identified.

Results：1) The baseline PRL levels of female schizophrenics(74.3±49.6ng/ml) were significantly(p<0.005) higher than those of males(36.3±24.6ng/ml), which were significantly(p<0.0001 respectively) higher than those of controls(females 16.9±6.1ng/ml, males 13.3±4.9ng/ml). The PRL levels measured on the 2nd wks(females 133.7±47.8ng/ml, males 56.9±23.6ng/ml) and on the 4th wks(females 146.1±45.9ng/ml, males 70.0±31.5ng/ml) after risperidone administration were significantly(p<0.0001 respectively) higher in females. The mean dosages of risperidone on the 2nd wks were 3.8±1.7mg(2-6mg) for the females and 4.0±1.6mg(2-6mg) for the males, and on the 4th wks were 4.5±2.1mg(2-8mg) for the females and 5.4±2.2mg(2-8mg) for the males. 2) The rise of PRL levels were positively correlated with increased risperidone dosage in males(γ＝0.307 on the 2nd wks and γ＝0.280 on the 4th wks), while they were not correlated with dosages in females. For the females, the PRL levels were negatively correlated(γ＝-0.320) with decrease of TSH concentration. The baseline PRL levels were not correlated with age, education, duration of illnesses, psychopathology, cognitive disorders in both males and females, while it was negatively correlated with TSH levels only in females(γ＝-0.320). 3) The cognitive dysfunction was not correlated with PRL levels in males, while PANSS-CF scores were negatively correlated with PRL levels(γ＝-0.220 on the 2nd wks and γ＝-0.366 on the 4th wks) in females. The psychopathology was positively correlated with cognitive dysfunction in both males and females. Therefore, the risperidone-induced cognitive improvement seemed to be correlated with improvement of psychopathology in both males and females, and with increase in PRL levels only in females.

Conclusions：The fact that the serum PRL levels of schizophrenics were higher than those of controls, especially in females suggested that it could be related with risperidone dosage in males and with primary pathological process in females. The risperidone-associated cognitive improvement seemed to be related with general improvement of psychopathology as well as the rise of PRL levels especially in females. The facts that the effect of risperidone-induced hyperprolactinemia and the cognitive function were more in females suggested that somewhat different mechanisms could be exerted on them.

Schizophrenia;Risperidone;Prolactin;Sex differences;Cognitive dysfunction.

Conventional high-dose antipsychotics tend to result in more side effects, negative symptoms and dysphoria, and at the same time lower the cognitive function which is already impaired in most schizophrenics. Florid psychotic symptoms, negative symptoms and cognitive impairment greatly impede psychosocial performance and eventual reintegration into society. The reduction of symptom and the improvement of cognitive funtions and social skills are therefore central to the psychiatric rehabilitation process. The purpose of this study was to evaluate the dose-reduction effects of antipsychotics on chronic schizophrenics prescribed conventional high-dose antipsychotics more than 1,500mg equivalent of chlorpromazine. Fifty-one chronic schizophrenics who maintained high-dose antipsychotics for more than three months were randomly assigned to two groups：20 patients comprised the dose-maintaining group and 31 patients made the dose-reduction group. Over a sixteen weekperiod Positive and Negative Syndrome Scale(PANSS), Extrapyramidal Symptom(EPS), Nurses' Observation Scale for Inpatient Evaluation(NOSIE-30), Continuous Performance Test(CPT), Quality of Life(QOL), and haloperidol/reduced haloperidol blood levels were determined at the base line and after 2, 4, 6, 8, 12, 16 weeks to evaluate the dose reduction effects of high-dose antipsychotics. The results were as follows：1) Dose-reduction is highly effective in reducing positive and negative symptoms, and general psychopathology. Effects were most prominent at 8, 12, 16 weeks. Among the dose reduction group, positive symptoms in positive symptom group and negative symptoms in negative symptom group were more reduced. 2) Extrapyramidal symptoms showed no significant difference between two groups. But the EPS was reduced time after time within two groups. 3) Hit rates of Continuous Performance Test, which indicate attentional capacity, increased significantly after dose reduction. 4) Haloperidol and reduced haloperidol blood levels decreased until the 4th week, after which they were constant. 5) Total scores of Nurses' Observation Scale for Inpatient Evaluation were unchanged between the two groups. But among the indices, social interest and personal neatness were improved in the dose-reduction group and retardation was aggrevated in the dose-maintaining group. 6) Total quality of life scores were unchanged between two groups. But in the dose maintaining group, satisfaction scores of attention, autonomy, and interpersonal relationship decreased progressively. These findings suggest that the dose reduction of antipsychotics for chronic schizophrenics on programs of high-dose antipsychotics were effective. Dose reduction should therefore be implemanted to spread the rehabilitation and improve quality of life for chronic schizophrenics.

Antipsychotics;Dose-reduction;Chronic schizophrenics.

Various neurotransmitters have been proposed as possible mediators of penile erection. Especially, norepinephrine and serotonin might have a important role in sexual arousal and penile erection. And it could be hypothesized that the psychogenic impotence is associated with the depletion or imbalance of norepinephrine and serotonin from evidences, such as the symptomatic manifestation of depression and the antidepressant-induced sexual dysfunction. The authors investigates the association of norepienphrine and serotonin with psychogenic impotence. The psychogenic impotent group(PIG) consisted of twenty-three patients with psychogenic impotence and the controlled group(CG) consisted of twenty-seven patients without psychogenic impotence. PIG had no organic cause accounting for their erectile dysfunction. The Beck Depression Inventory(BDI) and the State-Trait Anxiety Inventory(STAI) were applied to each subject to assess mood, state anxiety(SA) and trait anxiety(TA). Plasma norepinephrine level from systemic blood and 5-hydroxyindoleacetic acid(HIAA) levels from 24-hours urine were measured in each subject. The mean score of BDI of PIG was significantly higher than that of CG(p＝0.015). PIG had a tendency of higher TA compared with CG(p＝0.054). And also SA was higher in PIG, but did not show significant difference(p＝0.193). The level of norepinephrine was significantly lower in patient with psychogenic impotence(p＝0.000). And the level of 24-hours urine 5-HIAA was lower in PIG but did not show significant difference(p＝0.494). Although the authors did not exclude depressive disorders in PIG, the present findings suggest that psychogenic impotence might have higher depressive mood and trait anxiety, and be associated with the depletion of norepinephrine in systemic blood.

Psychogenic impotence;Depression;Anxiety;Norepinephrine;5-HIAA.

The mother was 24 years old, primipara, and had been taking carbamazepine 400mg(serum concentration 5.0-8.5μg/ml) during pregnancy without any clinical seizures. A male baby with physical malformation was delivered on week 39. The malformation is extradigit(polydactily) on X-ray of right foot and left mild hydronephrosis on ultrasonography and renal scan with radioactive material. We reported this rare case and reviewed related articles about teratogenic effect of carbamazepine, mechanism of action and prevention of teratogenesis.

Carbamazepine;Teratogenicity;Polydactily;Hydronephrosis.

Disturbances in memory are the most common problem in patients with an organic mental syndrome. Other patients with significant psychiatric disorders also often have difficulty with memory. So it is very important in the clinical practice of psychiatry to understand the biological and neurocognitive mechanisms of memory proessing, and to develop the assessment tools with which memory function can be evaluated reliably and validly. Moreover, memory researches provide an important viewpoint from which we can understand the pathophysiological mechanisms of major neuropsychiatric illnesses. This article focuses on our understanding of memory functions in clinical and neurobiological aspects. The relevant material will be presented in four parts：1) terminologies needed in defining major stages of various types of memory processing；2) neurochemical and neuroanatomical basis of memory processing；3) brief bed-side screening tests and more comprehensive neuropsychological tests for the evaluation of memory function；4) the characteristics of memory dysfunction in several major psychiatric illnesses.

Neurocognitive function;Neuropsychology;Psychiatric disorders;Memory.

In this article neuroanatomical theory and verbal developmental process were introduced, followed that disorders and assesment of language function were reviewed. Finally, the causes and assesment of developmental dyslexia as a childhood disorder related to verbal function were reviewed.

Language;Neuropsychology.

Attention is a phenomenon hard to define, but can be conceptualized as a mental function ranging from sustaining readiness to perceive stimuli to understanding the nature and value and selecting stimuli that are most relevant to the given situation. Manifestations of attention include vigilance, and focused, directed, selective, divided, and sustained attentions. While basic attentional tone is controlled by the interaction among reticular activating system, thalamus and prefrontal cortex, direction and selection of attention is controlled by neural circuits of prefrontal, posterior parietal, and limbic cortex. It is expected that understanding of attention and its neural control could provide answers to the relationship between pathophysiology and clinical symptoms of some major psychiatric disorders. More efforts are required to develop tools to assess more detailed and various aspects of attention in Korea.

Attention;Neural control;Psychiatric disorders.

Visual perception is a complex process engaging many different aspects of brain functioning. Like other cognitive functions, the extensive cortical distribution and complexity of visual perceptional activites make them hihgly vulnerable to brain injury. Dectection and characterization of perceptual disorders require a careful clinical assessment as well as the application of selected neuropsychological tests. In this article we reviewed neuropsychological assessment of visual perception and constructional abilities. And the principal visuospatial disorders are discussed, the associated neuropsychiatric disorders are presented.

Visual perception;Neuropsychological assessment;Neuropsychiatric disorders.

Many disorders in neuropsychiatric field demonstrate variable motor disturbances as their clinical feature or in their courses of illness and also due to psychopharmacological treatment. Although association of such motor disturbances with the pathophysiological aspect of various neuropsychiatric illness are still lacking, some form of motor disturbance offer a window through which pathophysiologic mechanism of such illnesses can be viewed. Cognitive control of motor functions are briefly reviewed in this article and the importance and method of motor function assessment in major neuropsychiatric disorders are also discussed. Motor dysfunction of major neuropsychiatric illness such as schizophrenia and mood disorders may offer a chance of a deeper understanding on the pathophysiologic aspect of their clinical presentation.

Motor function;Schizophrenia;Mood disorders.

Higher cognitive functions refer to the highest level of human intellectual functioning, including concept formation, reasoning, and executive functions. The executive functions can be conceptualized as having four components；volition, planning, purposive action, and effective performance. Because higher cognitive functions represent the most advanced stages of intellectual development, they are often highly susceptible to the effects of brain injuries and mental disorders. The ability to perform effectively within the environment is determined in large part by an individual’s adequacy in performing such higher-order functions. Especially executive functions are necessary for appropriate, socially responsible, and effectively self-serving adult conduct. Threfore, an assessment of the psychiatric patient’s performance in these areas will provide useful diagnostic information, as well as information concerning social and vocational prognosis.

Higher cognitive functions;Executive functions;Psychiatric disorders.

The author attempted to examine the allelic association between the A1 allele of Dopamine D₂ receptor and alcoholism in Koreans. The allelic distribution of Taq I polymorphism of the D₂ dopamine receptor gene with alcoholism was examined in 67 Korean alcoholics and compared with 100 Korean controls. In alcoholics, the numbers of alcoholics with A1A1, A1A2 and A2A2 were 11(16.4%), 30(44.8%) and 26(38.8%) respectively and in controls with A1A1, A1A2 and A2A2 were 17(17.0%), 42(42.0%) and 41(41.0%), respectively. The prevalence of the A1 allele in alcoholics was 61.2% and 59.0% in controls. And the frequency of the A1 allele in alcoholics and controls were 0.39 and 0.38, respectively. There was not significant difference in the frequency of the A1 allele between alcoholics and controls. This data suggest that the A1 allele is not associated with alcoholism in Koreans. The author conclude that our data do not support an allelic association between the A1 allele at Dopamine D₂ receptor and alcoholism. Further systemized studies will be necessary to determine whether the role of allele of Dopamine D₂ receptor is major effect gene or modifying effect gene in the pathogenesis of alcoholism.

Alcoholism;Dopamine D2 receptor;Allelic association.

CV(bDAT) cell line, expressing dopamine transporter stably, has been established by transfection of CV-1 cells with bovine dopamine transporter cDNA. Using CV(bDAT) cells, the effects of various antipsychotic drugs on dopamine uptake activity were investigated. All of antipsychotic drugs tested, inhibited the ［³H］dopamine uptake into CV(bDAT) cells with IC50s in the low to mid micromolar range, implying that antipsychotic drugs may produce overflow of dopamine in the synaptic cleft of dopaminergic neuron.

Dopamine transporter;Dopamine uptake;Antipsychotic drug.

Objects：Sanjoin, the seeds of Zizyphus vulgaris var. spinosus has been used as the most important hypnotic agent in chinese medicine to treat insomnia. This research was performed in order to examine the effect of betulinic acid and sanjoinine-A which are components of Sanjoin.

Method：Sleeping time, sleep recordings of EEG, EMG, serum serotonin level, and locomotor activity were measured in rats which received betulinic acid and sanjoinine-A as sleep induction material extracted from Sanjoin.

Results：1) Groups received betulinic acid, sanjoinine-A, and lorazepam showed increased sleep time than control group with saline. 2) Groups with betulinic acid, sanjoinine-A, lorazepam and saline recorded β-wave in sleep recordings of EEG. In EMG, there was no significant difference among all groups. 3) No significant difference in serum serotonin level among all groups was found. 4) In autonomic activity testing, groups of betulinic acid, sanjoinine-A, and lorazepam showed significantly more decreased in activity than saline group. In comparison of groups of betulinic acid and sanjoinine-A with a group of lorazepam, there was no significant difference.

Conclusion：These results suggest that betulinic acid and sanjoinine-A have the sedative effect like lorazepam rather than sleep effect.

Sanjoin;Sanjoinine-A;Betulinic acid;Serotonin;Sedative effect.

Objective：Accumulating evidence suggests a greater number of subcortical hyperintensities in the brain of patients with bipolar disorder. We studied the Clinical correlates of subcortical hyperintensities on magnetic resonance imaging in patients with Bipolar Disorder：

Methods：Magnetic resonance images of the brain were obtained for 32 patients with bipolar disorder. The presence and location of hyperintensities were assessed. We compared clinical variables between patients with subcortical hyperintensities and patients without them.

Results：Seven patients(21.8%) had subcortical hyperintensities, but among 8 patients who were 40 years or older, 5 patients(62%) had them. Age and age at onset of patients with subcortical hyperintensities were significantly older than patients without them. Psychotic symptoms were more frequent in patients with hyperintensities. Patients without hyperintensities had more familial loadings.

Conclusion：Given the limitations of the study, our results should be seen as preliminary. This study, however, provides preliminary evidence supporting the notion that the onset, clinical feature and course of some bipolar disorders of late onset may be determined by underlying subcortical abnormalities, with such abnormalities being the consequence of factors related to aging or neurodegeneration(such as impaired cerebral circulation) rather than genetic factors which predispose to early-onset bipolar disorders.

Magnetic resonance imaging;Bipolar disorder;Hyperintensity.

The changes of electroencephalogram(EEG) in patients with dementia are most commonly studied by analyzing power or magnitude in certain traditionally defined frequency bands. However because of the absence of an identified metric which quantifies the complex amount of information, there are many limitations in using such a linear method. According to chaos theory, irregular signals of EEG can also result from low dimensional deterministic chaos. Chaotic nonlinear dynamics in the EEG can be studied by calculating the correlation dimension. The authors have analyzed EEG epochs from three patients with dementia of Alzheimer type and three matched control subjects. The multichannel correlation dimension is calculated from EEG epochs consisting of 15 channels with 16,384 data points per channel. The results showed that patients with dementia of Alzheimer type had significantly lower correlation dimension than non-demented controls on 12 channels. Topographic analysis showed that the correlation dimensions were significantly lower in patients with Alzheimer's disease on frontal, temporal, central, and occipital head regions. These results show that brains of patients with dementia of Alzheimer type have a decreased complexity of electrophysiological behavior. We conclude that the nonlinear analysis such as calculating correlation dimension can be a promising tool for detecting relative changes in the complexity of brain dynamics.

Dementia of Alzheimer type;Chaos;Nonlinear;Dynamic;EEG;Correlation dimension.

With increasing tendency of incidence and interest for the late onset schzophrenia, concerns about whether this disorder is etiologically or phenomenogically distinctive entity or not have increased also. To clarify the disease entity of the late onset schzophrenia and the role of structural brain changes in its etiology, authors tried to prove following hypothesis：Are there any evidences of structural brain changes in the late-onset schizophrenia？；If present, are they not different from those of the early-onset schizophrenia or progressive schizophrenia？；And are they not different from those of senile dementia？ Subjects were 6 patients with the late-onset schizophrenia, 6 patients with the early-onset schizophrenia, 6 patients with progressive schizophrenia, 6 patients with Alzheimer's dementia, and 6 controls. We measured regions of interest of the magnetic resonance images by computer assisted planimetry using the AutoCad and digitizer. Our study results may suggest that the third ventricular enlargement and a reversal of normal difference between left and right temporal lobe and left-right difference in posterior lateral ventricle are common brain pathology for all types of schizophrenia including the late onset schzophrenia. And also suggest that brain structural changes of the late onset schizophrenia are related with neurodevelopmental abnormality rather than degenerative change.

Late onset schizophrenia;Early onset schizophrenia;Progressive schizophrenia;Senile dementia;Brain MRI.

This study was done to examine changes of plasma homovanillic acid(HVA), 5-hydroxyindoleacetic acid(5-HIAA), and HVA/5-HIAA ratio during an 8-week clozapine trial and to investigate the relationship between the plasma monoamine metabolites and treatment responses. Twenty-seven chronic schizophrenic patiens were treated for 8 weeks with clozapine. The psychopathology was assessed at baseline just clozapine trial and then every 2 weeks until the end of 8-week clozapine treatment using the Positive and Negative Syndrome Scale(PANSS) and the Clinical Global Impression scale(CGI). The plasma HVA and 5-HIAA levels were measured also biweekly using high preformance liquid chromatography with electrochemical detection method. Plasma HVA and 5-HIAA levels were significantly decreased during a 8-week clozapine treatment, although plasma HVA/5-HIAA ratio showed no significant change. The changes of plasma HVA levels were in significant correlations with the changes of PANSS positive scores, of general psychophathology scores, and changes of total socres. The changes of plasma 5-HIAA levels were in signfificant correlations with the changes of PANSS negative scores. But the changes of plasma HVA/5-HIAA ratio had no significant correlation with any PANSS subscale score changes. 48% of the patients treated with clozapine was categorized as responders, who showed at least a 20% decrease in PANSS total socre and a CGI severity score of mildly ill or less(≤3) at the end pint of the study. The baseline plasma HVA levels and HVA/5-HIAA ratio were significantly higher in responders(N＝13) than in nonresponders(N＝14). But no significant difference in baseline levels of plasma 5-HIAA was found between responders and nonresponders. At the end point of the study, there was significant difference in the change of plasma HVA between responders(40.3% decrement) and nonresponders(3.1% increment). But no signficant differences in the change of plasma 5-HIAA and the change of plasma HVA/5-HIAA ratio between responders and nonresponders were observed. These results suggest that the antipsychotic effect of clozapine on positive symptoms may be associated with dopaminergic blocking activity, and that on negative symptoms may be associated with serotonergic blocking activity. The baseline plasma HVA levels and the change of HVA levels from baseline may be useful predictors of treatment response with clozapine.

Clozapine;Therapeutic response;Plasma HVA;Plasma 5-HIAA;Chronic schizophrenia.

The recent hypothesis about the pathophysiology of schizophrenia has been centered mainly on two theories, i.e. dopamine hypothesis and serotonin hypothesis. We investigate the correlations between plasma monoamine metabolite concentrations and clinical symptoms in schizophrenic patients. The first purpose of our study was to examine whether the plasma levels of HVA(homovanillic acid) and 5-HIAA(hydroxyindoleacetic acid) are significantly different in schizophrenics, compared to normal controls. And, with the intention of clarifying the interaction between dopaminergic system and serotoninergic system, the ratio of HVA/5-HIAA also was measured. The second purpose was whether the basal(pre-treatment) levels of these metabolites show the correlation with clinical symptoms. Finally, third purpose was whether basal HVA and 5-HIAA levels can be held as a predictor of treatment response. We used Scale for the Assessment of Positive Symptoms(SAPS) and Scale for the Assessment of Negative Symptoms(SANS) as the clinical symptom rating scales. Our results were as followed, 1) only the level of basal plasma HVA was significantly differ in schizophrenics. 5-HIAA and HVA/5-HIAA were not. 2) basal HVA showed significant correlation with SAPS score, especially delusion subscale. 3) the higher was the basal HVA level, the more improvement in clinical symptoms was observed. The basal 5-HIAA level and the HVA/5-HIAA ratio did not show any significant findings. These results support the dopamine hypothesis of schizophrenia, but fail to examine on the possible involvement of serotonin in schizophrenia.

Schizophrenia;Plasma homovanillic acid;Plasma 5-Hydroxyindoleacetic acid;Positive symptoms;Negative symptoms.

Ginseng root, as a folk medicine, has been used in far eastern countries for thousands of years. Ginseng extract has been shown to have a variety of effects on the activity of the central nervous system, promoting stimulation as well as inhibition of the cortical activity. A survey of the relevant literatures has indicated that the putative anxiolytic activity of red ginseng has not been scientifically investigated. Therefore, the present study was designed to assess anxiolytic effect of gingseng total saponins(GTS). The putative anxiolytic effects of several fractions of GTS were investigated in mice using an elevated plus maze paradigm. Single dose administration of TS Fr.-I showed anxiolytic action in mice. Anxiolytic effect induced by TS Fr.-I was similar to that induced by diazepam. TS Fr.-II, TS Fr.-III and TS Fr.-IV did not show the anxiolytic action compared with that of TS Fr.-I. It was suggested that regulation of GABAergic neurotransmission may be important in the action of GTS. The Interaction of GTS fractions with benzodiazepine receptor was performed using rat cortical membranes. GTS inhibited the binding of [³H] Ro 15-1788 on the benzodiazepine receptor. Among from TS fractions, the binding activity of GTS in the TS Fr.-IV was highest, which did not show the anxiolytic activity. From these results, we conclude that GTS has anxiolytic action, and this is not related to benzodiazepine receptor binding activity.

Red ginseng;Total saponin fraction;Anxiolytic action.

The alcoholic neuropathies developed in approximately 34% of chronic alcoholics and the sexual dysfunction had been experienced in 8-54% of male alcoholics(Schiavi 1990). The aims of this study were to identify the prevalence of subclinical polyneuropathies and sexual disorders in alcohol dependence, and to evaluate the association between them. The nerve conduction velocity(NCV), electromyography(EMG), and pudendal somatosensory evoked potentials(SEPs) were tested for the male alcoholics(N=34) and controls(N=17 for NCV & EMG, N=25 for pudendal SEPs). The pudendal SEPs were measured by the following procedures, in which we stimulated the dorsal nerve of penis attached by the ring electrode(stimulus intensity, three times of threshold；stimulus rate, 1-4.7Hz；stimulus duration, 0.1 or 0.2msec), and recorded at the scalp(active electrode, 2cm behind Cz；reference electrode, Fz). The NCV and EMG detected signs of peripheral neuropathies in 79.4% of alcoholics. Among the alcoholics, 64.7% were abnormal on the pudendal SEPs. Among the alcoholics who revealed abnormality on EMG and NCV, 81.4% were abnormal on the pudendal SEPs, in which 51.9% were not responded. The P1 latencies of pudendal SEPs on neuropathic alcoholics were significantly delayed(p<0.05) than non-neuropathic alcoholics. There was a relative correlation between peripheral neuropathies and sexual disorders in the alcoholics. The prevalence of subclinical neuropathies and sexual disorders seemed to be much higher in alcohol dependence than expectation, and these two problems were relatively correlated, and our results suggested that the peripheral polyneuropathies were one of the prerequisites of sexual disorders.

Alcohol dependence;Peripheral neuropathy;Sexual disorders;Nerve conduction velocity;Pudendal SEPs.

This study investigated the antidepressant efficacy and it’s impact on the quality of life of depressed patients. We performed Hamilton Depression Rating Scale(HDRS), and Montgomery-Asberg Depression Rating Scale(MADRS), and Health-related Quality of Life Questionnaire(HQLQ) to both tricyclic antidepressant(TCA) and sertraline groups. There were 16 subjects in this study. The tricyclic group had 9 subjects and the sertraline group had 7. The TCA and sertraline produced a similar degree of response. Both groups experienced a reduction of 70% or more in mean HDRS and MADRS total score after 6wks. In HQLQ, the TCAs group also showed improved bed disability days, alertness behavior, and social interaction, the sertraline group showed improved health perception, alertness behavior, home management, and social interaction. We suggested that the improvement of “Quality of life” were not in proportion to the clinical symptom’s improvement. Therefore, clinicians should consider the benefit of antidepressant treatment in terms of quality of life.

Depression;Quality of life;Antidepressant.

Objectives：The authors have intended to know the drug interaction of fluoxetine and haloperidol when coadministering two drugs to the chronic schizophrenics by assessing the changes of positive, negative symptoms and extrapyramidal symptoms.

Method：We selected 38 patients, the chronic schizophrenics with no physical problems. they are randomly assigned to placebo group and drug group. And then, placebo or fluoxetine 20mg were administered to the subjects of each group during 8 week period. We have assessed their psychopatholgy and extrapyramidal symptoms using Positive and Negative Syndrome Scale(PANSS), Clinical Global Impression(CGI), Simpson-Angus Scale at 0, 2, 4, 6, 8 week during the period.

Results：38 patients have completed the study during 8 weeks. 1) PANSS, CGI：no significant difference between groups and no significant change according to the times. 2) Simpson-Angus Scale：no significant changes.

Conclusion：When co-administering fluoxetine and haloperidol, there were no significant changes of psychopathology and extrapyramidal symptoms. These results suggest that it is safe to coadminister fluoxetine to schizophrenic patients with haloperidol treatmemt.

Fluoxetine;Haloperidol;Drug interaction.

Objective：To evaluate the clinical efficacy of adjuvant sertraline treatment in chronic schizophrenic patients, we carried out a double-blind, placebo controlled study.

Method：Thirty six inpatients who fulfilled DSM-III-R criteria for chronic schizophrenia were randomly assigned to sertraline and placebo groups in a double-blinded fashion. A history of at least 2 years of illness and at least six months of hospitalization were prerequisities for inclusion in the study. Patients were received sertraline 50mg or placebo for 8 weeks in addition to their routine haloperidol regimen. Positive and Negative Syndrome Scale(PANSS), Clinical Global Impression(CGI), Simpson-Angus Scale(S-A) were evaluated at 5 points；baseline, 2, 4, 6, and 8 weeks of treatment.

Results：The groups were controlled for age, gender, and length of illness. There were no significant differences in three PANSS factros(positive, negative, general), CGI, and S-A scale scores at any between sertaline and placebo treatment.

Conclusion：This placebo controlled study showed no significant effects of sertraline on negative and positive symptoms in chronic schizophrenic patients.

Chronic schizophrenia;Double-blind;Sertraline;Haloperidol.

Current treatment strategies for levodopa-induced psychosis in advanced Parkinson’s disease have had limited success. Reduction or discontinuation of levodopa and coadministration with dopamine-blocking neuroleptics may attenuate the psychotic symptoms, but these strategies are associated with worsening of parkinsonian symptoms. Administration of 5-HT3 receptor antagonist；ondansetron, a newer strategy to attenuate psychosis of Parkinson’disease without motor deterioration was introduced. A 41-year-old young-onset male, who was diagnosed as Parkinson’s disease 7 years ago, was treated with levodopa therapy, and had levodopa-induced psychosis(delusion, hallucination, paranoid, insomnia). After trial of ondansetron, he showed improvement in the Brief Psychiatric Rating Scale(from 21 points to 9 points) in spite of increasing the dosage of levodopa. With ondansetron, we could increase the dosage of levodopa without psychotic complications(esp, hallucination), and he showed improvement in the motor fluctuation.

Levodopa-induced psychosis;5-HT3 receptor antagonist;Ondansetron.

We are report on three cases of typical clinical characterstics and treatment response in neuroleptic maligant syndrome(NMS), and reviewed the literatures of NMS. NMS was first recognized as a life-threatening complication of dopamine receptor antagonists, and defined as a catatonic-like states associated with fever, obtundation, muscle rigidity, and unstable vital sign in patients taking neuroleptic agents. Concepts of NMS have changed because medications other than classic neuroleptic drugs have been implicated as triggering agents and syndromes identical to NMS have been observed in other conditions. The important neurochemical features are probably functional dopamine deficiency and ensuing hyperactivity of excitatory amino acid neurotransmission in the basal ganglia and hypothalamus. Recognition of NMS and early discontinuation of neuroleptics are the most important step in its management. Supportive care includes management of hyperthermia and fluid replacement. Controversial therapeutic measures include the application of dopamine receptor agonists, excitatory amino acid antagonists, or dantrolene. Psychiatric patients with a history on NMS and psychotic relapse necessitating antipsycotics do not commonly redevelop NMS.

Neuroleptic malignant syndrome;3 cases;Overview.

Serotonin has been implicated in the etiology of many disease states and may be particularly important mental illness, such as depression, anxiety, schizophrenia, sleep disorders, suicide, eating disorders, obsessive compulsive disorders, migraine and others. Many currently used treatments of these disorders are thought to act by modulating serotonergic function. The identification of many serotonin subtypes, most of which have been shown to have functional activity and differential distribution, has stimulated considerable effort into synthesizing selective ligands(drugs) to help understand their significance. This should understand the role of serotonin in mental disorders and these new drugs can be studied alone and in combination with other treatments in order to clarify the parameters of drug use for the clinical effect.

Serotonin;Mental disorder;Serotonin receptor subtypes;Selective serotonin receptor drugs.

There is no doubt that dopamine plays a critical role in the etiopathogenesis of schizophrenia. However, there appeared some limitations in explaining the complex phenomena of schizophrenia. Recent research data suggest that dysfunction in serotonergic system may be involved. Before the dopamine hypothesis of schizophrenia became established, the interest in serotonin(5-hydroxytryptamine, 5-HT) as an etiological substrate of this illness occurred. Recently the importance and extent of 5-HT’s involvement in the pathophysiology and mechanism of action of antipsychotic drug is actively investigated. In recent years, therapeutic success of clozapine and risperidones has increased attention on the interaction between the 5-HT and dopamine systems in schizophrenia. This led to the concept of serotonin-dopamine antagonist for antipsychotics. The authors review the evidence for the role of 5-HT in schizophrenia and serotonin-dopamine interaction.

Serotonin;Schizophrenia;Serotonin-dopamine antagonist.

The serotonin has been known to play important roles in pathology of the mood disorders. We summerize the evidences of serotonin in pathology of the mood disroders in a view of neuroanatomical and neurochemical aspects. Nowaday, the selective serotonin reuptake inhibitors(SSRIs) may be practically the first line of antidepressants with traditional tricyclic antidepressants(TCAs). Authors review the role of serotonin in the treatment of the mood disorders, in a view of the general considerations in selecting antidepressants, pharmacology, therapeutic indications, side effects, doses of medication, drug-discontinuation syndrome, drug-to-drug interactions, and special therapeutic situations.

Serotonin;Mood disorder;Selective serotonin reuptake inhibitor.

The clinical efficacy of serotonin reuptake inhibitors such as clomipramine in the treatment of obsessive compulsive disorder(OCD) has fueled interest in the neurobiological basis of this illness. OCD is responsive exclucively to potent serotonin reuptake inhibitors clomipramine, fluoxetine, fluvoxamine, sertraline, and paroxetine and this point forms the important evidence supporting a cental role for serotonin in the pathogenesis of the disorder. Other serotonergic medications such as lithium, buspirone, trazodone, or fenfluramine may be useful as adjuvant treatments in treatment-refractory OCD and adjuvant antipsychotics are useful in tic disorders, personality disorders, and psychotic disorders. This paper reviews results of treatment studies, investigations of biological markers, and neuroendocrine challenges and implications for the role of serotonin in pathophysiology and treatment of OCD.

Serotonin;Obsessive-compulsive disorder.

Along with psychosocial factors of suicide, biological backgrounds of suicide are explored by extensive works mostly on biological markers, neurobiological models, genetic bases, and relationships with aggression and violence. The biology of suicide confers on neurotransmitters in central nervous system exploring metabolites, receptor binding affinities, neuroendocrine challenge tests in brain, cerebrospinal fluid, blood and etc. The major concerns with suicide are focused mainly on serotonin system：low CSF 5-HIAA concentration, higher 5-HT₂ receptor binding, and blunt prolactin response to fenfluramine. Postmortem study, in vivo study, genetic contributions, and some other issues such as suicidal methods, serum cholesterol, alcohol, and selective serotonin reuptake inhibitors are reviewed and discussed.

Suicide;Serotonin;Biologic marker.

Neural network models, also known as connectionist models or PDP models, simulate some functions of the brain and may promise to give insight in understanding the cognitive brain functions. The models composed of neuron-like elements that are linked into circuits can learn and adapt to its environment in a trial and error fashion. In this article, the history and principles of the neural network modeling are briefly reviewed, and its applications to psychiatry are discussed.

Back propagation;Biological psychiatry;Connectionist;Neural network.

To examine the double-faced thymoleptic(antidepressant and antimanic) effects of risperidone in mood disorders, this article reviews the psychotropic-induced mania, thymoleptic effects of antipsychotics, therapeutic effects of risperidone and risperidone(RIS)-induced mania(RIM) in mood disorders, risk factors of RIM, possible neurochemical mechanism of these thymoleptic effects, pathophysiological and clinical significance of thymoleptic effects, and suggestive clinical guideline of RIS in mood disorders. RIS appeared effective for bipolar disorder at a lower dose than that recommended for schizophrenia, especially in the cases of maintenance of mood stabilizers, and gradual titration from low doses. Manic induction/exacerbation can occur by chance during RIS treatment in mood disorders, schizoaffective disorders, and schizophrenias. The possible risk factors for RIM are refractory mood disorder, especially in bipolar I disorder with poor initial response；refractory schizoaffective disorders, especially in bipolar type with poor initial response；refractory chronic schizophrenias, especially with initial responses；psychotic features；higher initial doses；rapid titration；combined therapy with antidepressants in refractory depression；and RIS monotherapy in mania/hypomania. RIS is a drug that preferentially block 5-HT2 receptors. The effects of low dose are due mainly to the blockade of 5-HT2 receptors. There are more gradual increase in D2 blockade with increasing dose and this D2 blocking properties become apparent at higher doses. This may be related to a modulation of dopaminergic transmission by 5-HT2 antagonism at lower doses with the direct action of RIS on DA receptors coming into play at higher dose. The serotonergic antagonistic effect may be important for its effects on depressive symptoms. This, together with adequate blockade of D2 receptors, may not necessarily lead to destabilization of mood disorder, but rather to more therapeutic effects. Therefore, this dose-receptor affinity relationship with both antidepressant and antimanic effects according to treatment duration can explain a continuum of antidepressant effect, antimanic effect, behavioral stimulation, and manic/hypomanic induction/exacerbation. It was the recognition of a useful psychiatric side effects by a thoughtful observer with fertile minds that led to their ultimate utilization as psychotropic drugs, i.e., phenothiazine, MAOI, TCA, and lithium. And, in vivo pharmacological challenge by novel psychotropics, as a neurochemical probe, with more specific actions is a useful tool to select pharmacologically homogeneous subgroup of the same phenotypical(clinical) condition, to further study the unknown underlying pathogenesis of various mental illnesses. Finally, RIS may be a useful alternative or adjunctive drug for patients with mood disorders without psychotic features or refractory to treatment with standard antipsychotic drugs. The more conservative doses(tirated slowly from 1-3 mg/d) of RIS, and maintenance of mood stabilizer in the cases with risk factors of RIM are recommended in mood disorder.

Risperidone;Mood disorder;Double-faced thymoleptic effects;Psychiatric side effect;Manic induction/exacerbation.

The Bcl-2 protein has been shown to block apoptosis induced by a variety of stimuli. We have performed the experiments which cell death can be blocked by the bcl-2 proto-oncogene under moderate(50-100mM) or high ethanol treatment(400-600mM). As a result of morphological changes, and MTT assay, cell death was blocked by Bcl-2 under 100mM ethanol. However, the results of DNA fragmentation and RT-PCR(ICE, and CPP32), immunoblotting(CPP32, and PARP) for SK-pcDNA3 cells(vector only) and SK-Bcl-2 cells(stably expressed bcl-2 gene) were showen to be no significant differences between two cell lines. These results suggested that cell death induced by ethanol was not followed by apoptosis mechanism, and was blocked by the bcl-2 proto-oncogene with moderate ethanol.

Bcl-2;Ethanol;Apoptosis;ICE;CPP32;PARP.

The results regarding an association between the polymorphism sites in the dopamine D₁ receptor gene and schizophrenia compelled us to study the distribution of the polymorphism in Korean schizophrenia and controls. Eighty-eight schizophrenic patients and normal controls were examined by case-control study for distribution of the polymorphism of the dopamine D₁ receptor gene in Korean popualtion to minimize the effect of racial differencies in gene frequencies. The frequencies of the B₁ and B₂ in schizophrenic patients were 0.11 and 9.89, respectively. And 0.10 and 0.90 in normal control. Ther was no significant differences in the frequencies in the allele B₁ and B₂ between schizophrenic patients and normal controls. The author present here the evidence of a lack of alleic association between the polymorphism of the dopamine D₁ receptor gene and Korean schizophrenic patients. The assumption that the dopamine D₁ receptor gene has a genetic role in the development of schizophrenia was not suppoorted by this case-control study.

Schizophrenia;Dopamine D1 receptor;Alleic association.

The authors attempted to examine the allelic association between the A1 allele of Dopamine D2 receptor and schizophrenia, alcoholism, drug addiction in Koreans. Schizophrenic patients(n = 31), alcoholism(n = 65), drug addiction(n = 18) and controls(n = 52) were examined by case-control study for distribution of the TaqI polymorphism of the dopamine D2 receptor gene in Korean population to minimize the effect of racial differencies in gene frequencies. In schizophrenics, the numbers of schizophrenics with A1A1, A1A2, A2A2 were 9(29.0%), 15(48.4%) and 7(22.6%) respectively and in alcoholics with A1A1, A1A2, A2A2 were 14(21.5%), 36(55.4%) and 15(23.1%) respectively and in drug addiction with A1A1, A1A2, A2A2 were 2(11.1%), 10(55.6%) and 6(33.3%) respectively and in controls with A1A1, A1A2, A2A2 were 4(7.6%), 24(46.2%) and 24(46.2%) respectively. The prevalence of the A1 allele in schizophrenics, alcoholics, drug addiction and controls were 77%, 76.9%, 67% and 53.8% respectively. And the frequency of the A1 allele in schizophrenics, alcoholics, drug addiction and controls were 0.53, 0.49 0.39 and 0.31 respectively. There was significant difference in the frequency of the A1 allele between schizophrenics, alcoholics and controls. We also classified our alcoholic population. For classification by severity ,we used the median MAST score 30 in our samples. There was also significant difference in the frequency of the A1 allele between less severe group(0.42) and more severe group(0.57). This data suggest that the A1 allele is associated with schizophrenia and alcoholism in Koreans. Furthermore the prevalence of the A1 allele increassed in more severely affected alcoholics. The authors conclude that our data support an allelic association between the A1 allele at dopamine D₂ receptor and schizophrenia, alcoholism. These results suggest the A1 allele of the DRD₂ gene is associated with a number of behavior disorders in which it may act as a modifying gene rather than as the primary etiological agent.

Schizophrenia;Alcoholism;Drug addiction;Dopamine D2 receptor;Allelic association;Modifying gene.

Though initial report from Japan showed positive association of schizophrenia with dinucleotide repeat polymorphism in the NT-3 gene, subsequent studies showed mixed results. Therefore we conducted a replication study with Korean schizophrenics and matched controls who share similar ethnic background with Japanese population. The frequency of allele of dinucleotide repeat at 147 base pairs in the NT-3 gene was slightly increased, however, failed to reach statistical significance(χ²=1.884, df=1, p<0.170) between the two groups. These findings do not support an association of NT-3 gene polymorphism with schizophrenia in Korean sample.

Neurotrophin-3(NT-3);Dinucleotide repeat polymorphism;Association study;Schizophrenia.

The study was designed to evaluate the significant roles of SSRI in rat of depression model. Chronic exposure to mild unpredictable stress has been found to depress the consumption of sweet 1% sucrose solutions in the Sprague-Dawley rats. We applied the variety of 11 types of stress regimens and identified depressive behaviours(developed by Willner) in 70 Sprague-Dawley rats. Rats in experiments were stratified into 6 groups, ie；3 kinds of SSRI(paroxetine, fluoxetine, sertraline), clomipramine, choline and saline control. Memory function was evaluated by passive avoidance learning and retention test. The authors determined how long memory retention would remain improved with 24 hour, 1 week, 2 weeks, 3 weeks, and 4 weeks at training-testing interval in depressive states of the Sprague-Dawley rats. The results were as follows；1) There were no significant differences between the 6 groups at the 24 hour training-testing interval. 2) The paroxetine treated group showed significant differences from the control group at the 1 week and 2 weeks training-testing interval. 3) The paroxetine and the fluoxetine treated groups showed singificant differences from the control group at 3 week training-testing interval. 4) The paroxetine and the choline treated groups showed significant differences from the control group at 4 week training-testing interval. In summary, paroxetine had an effect on long term memory processing from 1st week to 4th week. Also, fluoxetine(at 3rd week) and choline(at 4th week) had effect on long term memory processing. Sertraline, clomipramine were ineffective on memory processing during 4 weeks observation. Possible explanations why paroxetine had early effect on memory processing than the other selective serotonin reuptake inhibitors are rapid bioavailability, which is the characteristics of pharmacokinetics of paroxetine. In clinical situation, author carefully suggest that SSRI would be beneficial to improve the memory function caused by depressive neurochemical changes.

SSRIs;Animal model of depression;Passive avoidance learning.

Tardive dyskinesia(TD) is a serious side effect of long-term treatment with neuroleptic medications. To investigate if glutamatergic hyperfunction is associated with TD, effect of MK-801 on the prevention and treatment of TD was studied using a rat model, ie, vacuous chewing movements(VCM). When comparing VCM scores of GroupI(haldol decanoate＋MK-801) with that of GroupII(haldol decanoate＋phosphate buffer saline), late measured VCM scores of former were significantly lower than that of latter, meaning that MK-801 is effective in the prevention of VCM. Furthermore, when MK-801(0.1mg/kg, 0.3mg/kg) is administered to VCM(＋) rats(VCM≥7/4min) of GroupII, VCM scores were significantly decreased, meaning that MK-801 is also effective in the treatment of VCM. From the above results, it is suggested that glutamatergic hyperfunction might be involved in the development of TD and MK-801 could be effective in the prevention and treatment of it.

MK-801;Tardive dyskinesia;Vacuous chewing movements(VCM).

The dysfunction of either or both noradrenaline and serotonin system are important in the pathophysiology of depression. Previous reports have suggested that there may be an important interaction between these two systems. Recently, some investigators have suggested that the combination of tricyclic antidepressants(TCAs) and selective serotonin reuptake inhibitors(SSRIs) would produce a rapid synergistic effect on down-regulation of either or both of these two systems and that this combination may produce a more rapid and absolute antidepressant effect. We compared the treatment efficacy, treatment associated side effects, treatment satisfaction, and the quality of life between the combination therapy of dothiepin-sertraline as well as the therapy of dothiepin alone in the treatment of major depressive disorder and dysthymic disorder. In our study, the combination therapy of dothiepin and sertraline produced a more rapid and absolute antidepressant effect than dothiepin alone. And the patients with combination therapy experienced relatively high treatment satisfaction than the patients with dothiepin therapy. The patients’ quality of life improved more rapidly in the combination therapy, especially, in the health perception, social behavior, and life satisfaction, than dothiepin alone. These results support the hypothesis that the combination of TCA and SSRI may produce a rapid synergistic effect on either or both norepinephrine and serotonin system, and more rapid antidepressant effect and high treatment satisfaction.

Depressive disorders;Combination therapy;Dothiepin·Sertraline.

The authors performed this preliminary study to investigate the effect of softening E.C.T. and propofol was compared to pentothal for induction of anaesthesia for E.C.T. on seizure duration. The results were follows；1) E.C.T. was performed in 60 psychiatric inpatients who were admitted during the study period. Of them 51.7% were diagnosed as schizophrenia, 21.6% as major depressive disorder, 16.7% as bipolar I disorder, manic and 10% of others. 2) Mean number of E.C.T. was 12.2 times a patient. 3) The most common target symptoms were persecutory delusion in schizophrenia, psychomotor retardation or agitation in major depressive disorder, and violent aggressive behavior in bipolar I disorder, manic. 4) Pre-ECT medication usually used were atropine 0.0093mgkg^-1, pentothal 2.76mgkg^-1 or propofol 1.42mgkg^-1. 5) The duration of seizure, as measured clinically, was reduced with propofol(20.5 sec) in comparison with pentothal(35.7 sec)(p<0.001). This suggests the possibility that additional treatments may be needed for the same clinical effect in psychiatric illness when propofol is used as the induction agent.

Electroconvulsive therapy;Target symptom;Duration of seizure;Propofol.

Objective：A 4-week, single-blind, parallel group study was conducted to evaluate the efficacy and safety of tofisopam and lorazepam in 32 outpatients with anxiety disorder.

Methods：Patients were randomized to receive either tofisopam(N＝17) or lorazepam(N＝15). The starting dose of tofisopam was 50mg t.i.d. daily, which could be increased to a maximum of 100mg t.i.d. according to the patient's clinical response and side effect. The starting dose of lorazepam was 0.75mg b.i.d. daily, which could be increased to a maximum of 1.5mg b.i.d. depending on the patient's clinical response and side effect. Efficacy evaluations at baseline, week 1, 2, and 4 used the 14-item Hamilton Rating Scale for Anxiety(HAM-A) and Clinical Global Impression(CGI). Tolerability was assessed by response to a nonleading question concerning adverse events. Laboratory parameters including vital sign, EKG, hematological, and biochemical values were measured during trial.

Results：No significant differences between HAM-A total scores, two HAM-A factors(psychic, somatic) and CGI severity scores were recorded at any point during tofisopam and lorazepam treatments. However, in each group there was a significant decrease in HAM-A total scores, two HAM-A factors(psychic, somatic), CGI severity scores over time. The pecentages of patients with tofisopam who at least minimally improved increased from 64.7% at week 1 to 94.1% at week 4. The pecentages of patients with lorazepam who at least minimally improved increased from 40.0% at week 1 to 66.7% at week 4. The pecentages of patients with tofisopam who had not any adverse event increased from 58.8% at week 1 to 87.9% at week 4. The pecentages of patients with lorazepam who had not any adverse event were not changed from 46.7% at week 1 to 46.7% at week 4. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial in both groups.

Conclusion：These data suggest that tofisopam may be effective in reducing anxiety and is a anti-anxiety drug of identical potency with lorazepam. Tolerability of tofisopam was superior to lorazepam. These findings should be confirmed by using double-blind crossover study with a large member of patients.

Tofisopam;Lorazepam;Anti-anxiety effect;Anxiety disorder.

Many investigators are trying to elucidate the pathogenesis of psychiatric disorders on the basis of neuroendocrine responses to stimulation or perturbation. Dexamethasone(DEX) suppression has been the most widely utilized as the prototypical challenge test. Dexamethasone suppression test(DST) has proven to be valuable in diagnosing the depressive spectrum disorder. Reported specificity of diagnosis of depression is relatively high, but sensitivity is limited. Some researchers used the combination of dexamethasone and corticotropin releasing hormone(CRH) in order to improve the sensitivity. They reported that combined DEX/CRH test is more sensitive than DST alone. In this study the authors modified the DEX/CRH test, i.e., we administered the insulin instead of CRH. Total subjects were 28(7 normal controls, 10 manic patients, 11 schizophrenic patients). Subjects were taken DEX(1.5mg p.o.) at 11 p.m., insulin 16 hours later(0.1 unit/kg i.v.). Five blood samples for the determination of cortisol and ACTH were serially drawn at 15 minute interval. The results are as followings：1) The cortisol and ACTH levels of manic subjects increased following insulin administration. Manic subjects showed higher levels of cortisol and ACTH than schizophrenic and normal control subjects. The cortisol and ACTH levels of schizophrenic and normal control subjects did not show gross changes. 2) The sensitivity of the test was lower than that of reported DEX/CRH test.

Combined DEX/IH test;Cortisol;ACTH.

Many studies have been conducted to search for the anatomical abnormalities in the brain which are etiologically related with schizophrenia. Generally schizophrenia in known to be related with decreased brain tissue, hypofrontality and abnormalities in the temporal lobe including the hippocamypus, the agmygdala and the entorhinal cortex. Other areas related with the disorder are basal ganglia, thalamus, brain stem, pons and nucleus accumbens. Abnormality in brain asymmetry is one of the now areas of interest which needs further study. The results so far are inconsistent and it is unlikely that the abnormality in one structure is the only cause of the disorder. Rather, schizophrenia develops from the impairment of the parallel processing of integrated and reciprocal information which is distributed to the multiple structures. Histopathologic studies in the postmortem brain suggest that schizophrenia is related with neurodevelopmental abnormality rather than neurodegenerative abnormality. 

Schizophrenia;Neuroanatomy.

Molecular genetic approaches contribute to the understanding of the underlying genetic mechanism for schizophrenia. Currently genetic evidence rests on molecular genetic methods. However, the results are contradictory and somewhat confusing due to genetic heterogeneity, incomplete penetrance, misspecification of genetic model. It is expected that molecular genetics could provide key answers to the genetic cause of schizophrenia. The purpose of this article is to call attention of the readers to heterogeneity, linkage, association, basic molecular genetic methods and genetic markers and to the need for further research. It is the author's hope that continuous research on the molecular genetics can provide clinicians with better understanding of the schizophrenia.

Schizophrenia;Linkage;Association;Candidate gene.

The introduction of chlorpromazine in the 1950's revolutionized the treatment of schizophrenia and ultimately ledto the development of selective D₂ antagonists such as haloperidol, a goal in keeping with the prevalent theories at that time. However, limitations in the efficacy of these agents, a growing awareness of their side effects, and theoretical shifts in our understanding of schizophrenia have encouraged ongoing efforts to develop better 'atypical' antipsychotics. Clozapine, and subsequently risperidone, represent examples of these novel compounds, both of which incorporate shared serotonin-dopamine antagonism(SDA). The next years will be dominated by further development of SDA compounds, although a number of other lines of investigation are also being pursued.

Schizophrenia;Role of serotonin;Serotonin-dopamine antagonism.

Tardive dyskinesia is a syndrome of involuntary hyperkinetic abnormal movements that occurs during or shortly after the cessation of neurolepitc drug treatment. Typically, the movements are choreoatheoid. Other movements such as tics and systonia may be present. Nonetheless, any dyskinesia seen in a neuroleptic-treated patient is not always neuroleptic-induced tardive dyskinesia. The prevalence of tardive dyskinesia varies widely, which reflects many methodological problems, such as differential diagnosis, symptom fluctuation, masking effect of neuroleptics, validated diagnostic criteria. Of suggested risk factors, only old age has been consistently found to be associated with an increased frequency of tardive dyskinesia. Many hypotheses about the pathophysiolgy of tardive kinesia are proposeed, but time-honored ones are not present. No consistently safe and effective treatments are found. Various treatment modalities signifies the general ineffectiveness of these agents for most patients. In general, reduction or cessation of neuroleptics, if possible, is recommanded. Remission or improvement of tardive dyskinesia after neuroleptics withdrawal usually occurs among most patients within three months.

Tardive dyskinesia;Neuroleptics;Antipsycliotics.

Recent studies on long-term outcome of schizophrenia revealed that schizophrenic symptoms recover in more than 50%, while it remains severe in less than 20% after 20 years or more from the onset. Psychophamacological studies indicate that 75% of remitted schizophrenics may recur within 2 years after discontinuation of maintenance pharmacotherapy. In addition, family studies revealed that schizophrenic decompensation may occur significantly more frequent in discharged patients with high expressed emotion family than in low expressed emotion family. These findings may occur significantly more frequent in discharged patients with high expressed emotion family than in low expressed emotion family. These findings strongly support a clinical validity of stress-vulnerability concept of schizophrenia which open a new viewpoint to two central problems in schizophrenia treatment, i.e. psychotic relapses and chronification of the first episode schizophrenia. Moreover, recent psychopathological studies argue that schizophrenic symptoms are manifestations of psychological reaction secondary to a primary cognitive impairment(neurobiological vulnerability), which is originated in neurobiological changes in the brain. Recent approaches to the vulnerability to schizophrenic symptoms or schizophrenic decompensation are reviewed.

Schizophrenia;Stress-vulnerability concept;Cognitive impairment;Relapse;Refractoriness;Reverse;Reverse tolerance phenomenon;Methamphetamine psychosis;Dopamine.

This study was designed to examine the basal cyclic AMP levels and the 10^-5mol/L isoproterenol-stimulated cyclic AMP levels of lymphocytes, by which B-adrenoceptor function was shown, between 10 normal controls and 17 drug free patients(8 major depressive patients and 9 dysthymic patients), who were diagnosed by DSM-III-R. The severity of depression was assessed by Hamilton Rating Scale for Depression(HDRS). Cyclic AMP levels were measured by radioimmunoassay(double antibody). The results were as follows ; 1) HDRS score was significantly higher in major depressive patients(41.8±4.6) than in dysthymic patients(24.0±4.2)(p<0.05). 2) There was no significant difference in basal cyclic AMP levels among normal controls(3.9±1.7 pmol/10⁶cells/10min), major depressive patients(2.1±0.5 pmol/10⁶cells/10min), and dysthymic patients(3.9±1.8 pmol/10⁶cells/10min). 3) There was significant difference in net cyclic AMP levels(10^-5mol/L isoproterenol-stimulated cyclic AMP levels minus basal cyclic AMP levels) among normal controls(16.5±6.0 pmol/10⁶cells/10min), major depressive patients(3.0±1.4 pmol/10⁶cells/10min), dysthymic patients(10.9±4.4 pmol/10⁶cells/10min)(p<0.05). 4) The net cyclic AMP levels were significantly correlated with HDRS scores in major depressive patients(y=-0.8⁶, p<0.05), but not in dysthymic patients(y=0.43, p=0.25). In conclusion, we suggested that the dysthymic disorder might differ from the major depressive disorder not only in the severity of depressive symptoms but also in B-adrenergic responsiveness of lymphocytes, which was regarded as a biological marker of depressive disorder.

Major depressive disorder;Dysthymic disorder;Isoproterenol;Cyclic AMP;B-adrenoceptor.

The effects of 3 week treatment with haloperidol(2mg / kg / day, i.p.) on dopamine(DA) D2 receptor and DA metabolism in rat striata were studied at various time points after withdrawal form the drug treatment. Striatal DA D2 receptors were characterized with the radioligand 0.5nM [³H]spiperone. Dopamine(DA), homovanillic acid(HVA), 3,4-dihydroxyphenyl acetic acid(DOPAC) in rat striatum were measured with the high performance liquid chromatography. Drug withdrawal for 1 week induced significant increase in the number of D2 receptor in striatum after withdrawal for 1 week(p<0.05), and then this change was restored to control level during the withdrawal time of 2 and 4 weeks. There was no difference in striatal concentrations of DA and its metabolites among the groups. In conclusion, one-week withdrawal from chronic haloperidol treatment induced DA D2 receptor supersensitivity in the srtiatum, and that was normalized rapidly. Though this adaptive change in DA receptors, it may not affect the metabolism of DA in striatum.

Dopamine receptor supersensitivity;[³H]spiperone binding;Haloperidol withdrawal.

The Evaluation of patients complaining of psychiatric symptoms following head injury is much affected by the results of various tests. The objective of this paper is to investigate the effectiveness of each test by comparing the structural and functional brain studies. The subjects were 93 organic mental disorder in and out patients at the Dept. of Neuropsychiatry of the Kyung Hee University Hospital. After carrying out MRI, CT, SPECT, EEG, the results of each were analysed for the sesitivity and ability to detect focal lesion. The degree of interest correlations of test results were also investigated. Furthermore, the characteristic features of psychological tests were studied and the relationship between each of above mentioned tests and psychological test was examined. As for the test sensitivity to diagnosis, the SPECT was the most superior followed by MRI, CT, EEG in that order. In the case of abnormality, SPECT ranked 1st in detection of focal lesion, followed by MRI, CT in thar order. In the interest result correlated significantly with that of MRI finding. In the MMPI, the average scores on F, Hs, D, Hy, Pa, Pt, Sc subscales were above 60. Abnormal SPECT group scored significantly high on the F, Pd, Pa, Sc, Ma scales and therefore in comparison to the SPECT normal group, displayed more psychotic features. In K-WAIS, the mean full scale IQ and abnormal SPECT, MRI, CT and EEG results. In conclusion, 1) The SPECT was most superior in sensitivity and detection of focal lesions. In comparison with other tests, the results of SPECT correlated well with MRI and thus is thought to be very useful testing method in the evaluation of organic mental disorder patients. 2) The MRI had relatively high sensitivity, ability to detect focal lesion and superior correlation with other test. 3)Although EEG fared less on sensitivity in comparison to other test, of above moderate abnormal grade group and that of MRI correlated significantly. 4) In the MMPI highly scored in F, Hs, D, Hy, Pa, Pt, Sc subscales and abnormal SPECT patients were shown to display more sever psychotic features. There was no significant character relationship between the lowered IQ(in K-WAIS) and abnormal findings on MRI, CT, SPECT, EEG.

Post-traumatic organic mental disorder;MRI;CT;SPECT;EEG;Psychological tests.

There has been an increase in head trauma due to rapid industralization and improvement in transportation. This poses difficulties in differentiating between neuropsychiatric disabilities resulting from real organic changes and those arising from compensation issues. It is the purpose of this study to seek out the differences between normal and abnormal finding group in the structural brain imaging studies via the results of the functional brain imaging studies and psychological tests. Out of 132 subjects, 62 comprised normal and 70 the abnormal finding group. EEG and SPECT were chosen for inspection of functional brain imaging. MMPI and K-WAIS were chosen for psychological test. The subjects were further divided into right hemispheric damage, left hemispheric damage, both hemispheric damage, diffuse damage group and negative group in order to find out whether any differences in the psychological test results could be localized. The results are ad follows : 1) The abnormal finding group, the EEG and SPECT were proven to be a good predictor of brain lesion. This implies that even in the functional brain studies, abnormalities are more easily detected if there are visible brain lesions. 2) The FSIQ of the abnormal finding group is lower than that of normal finding group. This difference is mainly due to low VIQ. The left hemispheric damage group tend to show low VIQ. This lowered in VIQ was the difference between left hemispheric damage group and negative group. Furthermore, there were no group differences in the PIQ. It is concluded that K-WAIS is effective as evaluator of VIQ mainly of those patients with left hemispheric damage and it is ineffective as a evaluator of PIQ. 3) In the MMPI profile, the both groups displayed high neurotic profiles. There was no difference in the psychotic profiles. The scores of the Depression and Hystery were high in abnormal finding group. This can be seen as one of the typical findings of chronic head trauma patients. 4) The abnormal finding group tend to be diagnosed as organic mental disorder in the psychological tests more frequently.

Head trauma;Structural brain imaging;Functional brain imaging.

Object : The aim of this study was to evaluate the changes of positive symptoms, negative symptoms, and depressive symptoms after fluoxetine trial in haloperidol-stabilized schizophrenic in-patients.

Method : Fluoxetine(20mg/day) was added for 6weeks to stable doses of haloperidol given to 32 schizophrenic in-patients. The subjects was divided into positive and negative schizophrenics by PANSS. The authors checked PANSS, HRSD at baseline, the 2nd week, the 4th week, the 6th week of treatment. 

Result were as follows : 1) In all subjects, positive and depressive symptoms were significantly improved. 2) As time went on, positive and negative symptoms were not significantly improved in positive and negative schizophrenics. 3) As time went on, depressive symptoms were not significantly improved in positive and negative schizophrenics.

Conclusion : We suggested that fluoxetine may be useful in the treatment of positive symptoms in schizophrenia and, It may be due to the effect on the serotonin system and the interaction between serotonin and dopamine system.

Schizophrenia;Serotonin;Fluoxetine;PANSS;HRSD.

The effects of disulfiram implantation therapy have three components : placebo, pharmacological, and psychological effects. However, considering the fact that there is no reported DER(disulfiram-ethanol reaction) in placebo implanted patients and the absorption of implanted disulfiram is not sufficient to produce DER, the major effect of disulfiram implantation is psychological rather than placebo and pharmacological one. Recently, there have been great efforts to develop a new form of disulfiram which could exert a real pharmacological effect through the heightened bioavailability. To illustrate several examples, there are copolymer consisting of disulfiram and polymer such as polyethylene glycol and PLGA(polyglycolic-co-L-lactic acid) and depot in which disulfiram is dissolved into saline solution containing 5% w/v carboxymethylcellulose or 0.1% ploysorbate 80. On the other hand, there has been a continuous research about Me-DTC, an active metabolite of disulfiram, which inhibit ALDH (acetaldehyde dehydrogenase) more potently even at a smaller amount than disulfiram. In the future, it is hoped to develop a new form of disulfiram with high bioavailability at a small amount.

Psychological effects;Bioavailability;Me-DTC.

In an open labeled study, two fixed doses of nimodipine(45mg and 90mg daily) were added to the usual antipsychotic drug treatment(Haloperidol ; mean dose=25mg.day) in 20 male chronic schizophrenics for 5 weeks. The purposes of this study were to evaluate the therapeutic effects and the effect on the changes of plasma homovanillic acid(HVA) and 5-hydroxyindoleacetic acid(5-HIAA) levels. The results were as follows : 1) Total BPRS score and thought cluster, paranoid cluster subscores showed linear decreasing trend over the course of the study(P<0.05). Especially the thought cluster and paranoid cluster subscores were significant difference between 45mg and 90mg dose of nimodipine(P<0.05). The improvement rates were 45.45% of 90mg and 11.11% of 45mg, but there was no significant difference between the 45mg and 90mg dose of nimodipine. 2) The scores of extrapyramidal symptoms and adverse events-somatic symptoms showed a linear decreasing trends over the course of study. 3) The changes in the mean plasma HVA and 5-HIAA concentrations by the dosages and durations of combining of nimodipine were not statistically significant. Nimodipine has a possibility as an adjunctive agent for treatment resistant schizophrenics, elderly patients and liable patients for the side effects to usual antipsychotic drugs. So we suggest that the dosage of nimodipine must be above 90mg/day in the treatment of schizophrenia.

Calcium channel blocker;Plasma HVA and 5-JIAA;Treatment resistant schizophrenics.

Objects : There has been the controversy that menopause may or may not influence the psychological distresses. The purpose of this study was to investigate the correlation between the hormonal status and traits of depression & anxiety in menopausal women.

Method : Among the women attending menopausal clinic, menopausal wonmen, defined as who having a amenorrhea for more than 12 months, were selected as a study group(n=83). The control group(n=73), who visited to screen the cervix cancer with regular menstruation, had no history of hormone replacement therapy. Individual data were collected by self-reporting questionnaires. Depression state was evaluated by Beck Depression Inventory(BDI) and anxiety state by State Trait Anxiety Inventory(STAI), and the female hormones such as E2, FSH, and LH were obtained by blood sampling at visiting clinic. Statistically th data were processed by t-test and pearson correlation analysis(p<0.05).

Result : 1) The mean age of menopausal was 45.3 years. 2) In menopausal women the scores of BDI & STAI were significantly higjer than in control group(p<0.05). 3) There were significant differences between menopausal and control group by E2 & FSH. 4) There was no correlation between female hormonal status and the STAI & BDI scores in both group.

Conclusion : Although menopausal women had more traits of depression & anxiety in menopausal period. In further studies, we must consider another factors, including biological, sociocultural, psychological factor, as the cause of psychological symptoms during menopausal period.

Menopause;E2;Depression;Anxiety.

This was an open trial to evaluate the efficacy and safety of moclobemide twice daily for treatment of Korean patients with major depressive disorder(DSM-III-R). The duration of the trial was 6 weeks with initial dose of moclobemide being fixed for the first two weeks at 300mg/ day(150mg twice daily, each taken after morning and evening meals). Thereafter, when necessary, the dose was allowed to increase to 600mg/day or decrease to 150mg/day according to the severity of the depression and/or the tolerability of the drug. Hypnotics and/or sedatives from a benzodiazepine group could be concomitantly administered at usual dosage. Patients were assessed at baseline and at days 14, 28 and 42. Efficacy was primarily judged on the Hamilton Rating Scale for Depression(HAM-D) and Beck Depression Inventory(BDI). Patients had to score at least 17 respectively on both scales to enter the trial. Secondary efficacy parameters included Clinical Global Impression(CGI) for severity of illness and improvement. Safety and tolerability were judged on reported adverse events, vital signs and laboratory parameters. In addition, there was a series of questions and assessments for the psychiatrists and patients to complete at the end of the trial. Twenty nine patients completing trial were included in the analysis of efficacy ; of thirty one patients participating in the safety and tolerability analysis, those who withdraw voluntarily without particular reasons or violated the treatment schedule were not included. The efficacies as determined by HAM-D, BDI or CGI were found to be significant compared to vaseline. The number of responders defined as patients with a total score of 10 or less or with a total score of 50% or less of the baseline score on HAM-D and BDI were 17(59%) and 18(62%) respectively. Regarding safety and tolerability, nine patients(29%) reported mild adverse events probably related to moclobemide ; of these one patient dropped out because of poor tolerability ; however, there were no appreciable changes in blood pressure, pulse rate, body weight or laboratory parameters for all patients over the trial period. Furthermore, the physicians' and patients' opinions at final evaluation showed that moclobemide has a good antidepressant effect as well as a favorable tolerability. In conclusion, a twice-daily dosage schedule with moclobemide is recommendable for the treatment of Korean patients with major depressive disorder since its efficacy and safety were demonstrated in this study.

Moclobemide;Efficacy;Safety;Major depressive disorder.

We have previously reported that Korean schizophrenic patients have low production of IL-2 in vitro suggestive of autoimmunity to the pathogenesis of the disorder. In an attempt to further explore this issue, we measured in vivo serum levels of interleukins(IL-1β, IL-2, and IL-6) using a quantitative "sandwich" enzyme immunoassay(ELISA) in 26 age-matched normal controls. Patients met DSM-IV criteria for schizophrenia and were drug free for at least six months. The severity of symptoms was assessed by SANS and SAPS. We found a significant increase of IL-2 level(p<0.05) in schizophrenic patients as compared with normal controls. There were significant positive correlations between IL-2, IL-6 levels and negative symptom scores. There were no correlations between age, age at onset, duration of illness and interleukin levels. Our results may support the hypothesis of viral-autoimmune dysfunction in schizophrenia. IL-2 or IL-6 may be associated with specific clinical feature in schizophrenic syndrome, especially negative symptom.

Interleukin;Viral-autoimmune hypothesis;Schizophrenia.

To investigate characteristic drug effects on the genetic basis, the authors administered haloperidol- the D2 antagonist- and clozapine -the atypical antipsychotics with few extra- pyramidal side effects- to the rats. Then, we edobtain brain specimen from the striatum, prefrontal cortex, and cortical region and compared the degree of c-fos expression. The results are 1) haloperidol was found to produce a rapid and transient induction of c-fos mRNA expression in striatum as compared with cortex and prefrontal area. 2) clozapine was found to produce rapid induction of c-fos mRNA in striatum and prefrontal area. 
3)From these data, we can concluded that the mechanism of action of haloperidol is different from the mechanism of clozapine in gene expression.

Haloperidol;Clozapine;c-fos.

Object : There is considerable interest in the role of serotonin(5-HT) in the pathophysiology of schizophrenia. Cimetidine, H₂ antagonist, produces transient increase in serum prolactin(PRL) levels by indirect serotonergic mechanism in man following intravenous administration. Therefore the authors investigated the effects of cimetidine on serum PRL levels of male unmedicated schizophrenics.

Method : Baseline serum prolactin level and psychopathology were measured at 9 : 00 AM. in the two groups(12 positive schizophrenics, 7 negative schizophrenics) and T₃₀ level were measured 30 minutes after intravenous injection of cimetidine(ie, 9 : 30 AM)

Result : 1) Baseline prolactin levels were not different in the three groups. 2) prolactin levels of 30 minutes after intravenous injection of cimetidine(T₃₀) compared with baseline prolactin levels were increased all in the three groups. 3) Degrees of interval change from baseline to T₃₀ were significantly different between normal control and negative schizophrenics(p<0.05).

Conclusion : The prolactin response to cimetidine was significantly blunted in negative male schizophrenics than normal control. These data are consistent with the hypothesis of an abnormality of serotonergic activity, including down-regulation of 5-HT₂ receptors, in male negative schizophrenics.

Cimetidine;Prolactin Serotonin;5-HT receptor;Schizophrenia.

In recent year, problems coused by the abuse of drugs have been analyzed in many cases, especially women's pregnancy. The purchasing of drugs without prescription, the misunderstanding of symptoms of pregnancy(such as vomiting, headache) as other ilnnesses, taking medicine during the pregnancy because of a chronic disease has caused many unfortunate cases. Apart from these cases, pregnant women may take several medicines such as anadyne, tranquilizers, hypnotics, and diuretics which also cause critical situations. According to Piper and his colleague's 1987 study, in average, pregnant women in the United States intake 3.1 kinds of additional drugs other than prenatal vitamins and mineral supplements. In those cases, both pregnant women and physicians anticipate inborn deformity. Most drugs which have whole body effects get to the unborn child via the placenta, however, many of these drugs do not have adverse effects(Shepard 1986, 1989). In general, drugs present a stronger effect to unborn children than they do to pregnant women due to the body's excretion and to the drug metabolism that occurs in the mother's body through the placenta. The effects of drugs on unborn children show different results, depending upon the type of drug, dosage, characteristics, gestational weeks, genetic characterisitics of the mother an body, and many other environmental factors.

Drugs;Teratogens;Pregnancy.

Doctors who treat pregnant women are usually cautious in writing their prescription for the drugs. The problem of which psychotropic medications are safe during pregnancy seems to remain unsolved for many years. Although the rate of absorption is reduced due to a reduced rate of gastric emptying, the extent of absorption of drug is generally unchanged during pregnancy. Plasma volume and total body water increase during pregnancy. There is suggestion that drug metabolizing activity may be increased in pregnancy. Since the pregnancy increase the glomerular filtration rate significantly, drugs mainly eliminated by renal excretion will be cleared more quickly. Factors contributing to the potential teratogenecity of a drug include the type of compound, dose and duration of use, developmental stage of fetus at the time of exposure, and the effect of the drug on fetal pharmacokinetics. All major classes of psychotropic agents should be assumed to diffuse readily across the placenta to the fetus and to be present in some quantity in the breast milk. To decide when and how to start the drug treatment depends on an assessment of the risks related both with and without drug treatment of psychiatric disorders.

Pregnancy;Lactation;Pharmacokinetics;Psychotropic agent;Teratogenicity.

Many pregnant women have to receive psychotropic medication during pregnancy and lactation period, despite the proven and assumed risks to the fetus or neonate. A brief summary of drug metabolism and pharmacodynamics is given. Principles and quidelines of using psychotropic agents during pregnancy and lactation period are presented for psychotic disorders, bipolar affective disorders, depression and anxiety disorders, with due consideration for relative benefits and risks of choosing among psychotropic drugs and alternative treatments.

Pregnancy;Psychiatric patients;Pharmacotherapy.

An association study with Korean schizophrenic patients(N=75) and normal controls(N=87) was performed to find the relationship between D6S274 polymorphism and schizophrenia using polymerase chain reaction. Nine different alleles of a dinucleotide polymorphism on D6S273 locus were observed in both group. When we compared the frequencies of alleles between schizophrenics and normal controls, there was no significant difference between two groups. To increase homogeneity of schizophrenic group, we divided schizophrenic group by clinical phenotypes such as DSM-IV diagnostic subtype, family history, negative and positive symptoms(PANSS), soft neurologic signs(NES-K). Then we compared the frequencies of alleles among subgroups of clinical phenotypes, there was only significant difference between two subgroups on soft neurologic signs(p<0.05). Although our findings fail to provide an evidence of association between schizophrenia and D6S274 locus, follow-up investigation of this locus may be needed in homogeneous subtypes of schizophrenia and schizophrenic pedigrees.