Korean Journal of Biological Psychiatry

Many psychiatric disorders are associated with brain functional dysfunctions and neuronal degeneration. According to the research so far, enhanced brain plasticity reduces neurodegeneration and recovers neuronal damage. Brain-derived neurotrophic factor (BDNF) is one of the most extensively studied neurotrophins in the mammalian brain that plays major roles in neuronal survival, development, growth, and maintenance of neurons in brain circuits related to emotion and cognitive function. Also, BDNF plays an important role in brain plasticity, influencing dendritic spines in the hippocampus neurogenesis. Changes in neurogenesis and dendritic density can improve psychiatric symptoms and cognitive functions. BDNF has potent effects on brain plasticity through biochemical mechanisms, cellular signal pathways, and epigenetic changes. There are pharmacological and non-pharmacological interventions to increase the expression of BDNF and enhance brain plasticity. Non-pharmacological interventions such as physical exercise, nutritional change, environmental enrichment, and neuromodulation have biological mechanisms that increase the expression of BDNF and brain plasticity. Non-pharmacological interventions are cost-effective and safe ways to improve psychiatric symptoms.

Brain plasticity; BDNF; Complementary Therapies.

Objectives  This study aimed to review the Korean Constitution articles 14 and 20 of the “Law on suicide prevention” and investi- gate public perceptions of specific improvements to suicide prevention policies using results from the Korean 2018 National Survey on Suicide.
Methods   The questionnaire was designed to analyzing the act restricts sharing of patient information between hospitals, making it difficult to track suicide attempts. The questionnaire was also designed to suggest further medical and normative criteria for objective judgment of continuous follow-up utilizing suicide risk evaluations and proportional principle review that consider patients’ and medical staff ’s basic rights.
Results  This study identified the result of the 1500 respondents, 79.1% believed that Korea should allow suicide prevention man- agement to be implemented without requiring individual consent to protect suicide attempters.
Conclusions   According the results, I propose the following criteria for policy improvement: use of anonymized information and non-profit research for technical and ethical considerations, access to medical information only for therapeutic purposes, and use of surgical severity assessment criteria appropriate for Korea.

Suicide prevention; Constitution law in Korea; Suicide prevention law; Suicide attempt; Personal Information Protection Act; Confidentiality and privacy.

Objectives  This study aims to develop valid experimental models for depression through chronic reserpine exposure to zebrafish (Danio rerio).
Methods  The effect of chronic reserpine on zebrafish behavior in the novel tank was examined. Changes of gene expression on telencephalon were also investigated.
Results  Chronic reserpine (40 mg/L, 7 days) induced overt behavioral effects, but markedly reduced activity, resembling motor retardation in depression. In telencephalon of zebrafish, gene expression associated with monoamine oxidase and norepinephrine transporter was decreased. Expression of serotonin transporter gene was increased.
Conclusions  Our results show that the pharmacological model of depression in zebrafish can induce not only behavioral changes, but also monoamine changes in the homology of human mood regulation centers.

Reserpine; Depression; Zebrafish; Animal model; Experimental model.

Objectives  Alzheimer’s disease (AD) is the most common form of dementia in older adults, damaging the brain and resulting in impaired memory, thinking, and behavior. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. The aim of our study was to identify differentially expressed genes associated with AD and combined biomarkers among them to improve AD risk prediction accuracy.
Methods  Machine learning methods were used to compare the performance of the identified combined biomarkers. In this study, three publicly available gene expression datasets from the hippocampal brain region were used.
Results  We detected 31 significant common genes from two different microarray datasets using the limma package. Some of them belonged to 11 biological pathways. Combined biomarkers were identified in two microarray datasets and were evaluated in a different dataset. The performance of the predictive models using the combined biomarkers was superior to those of models using a single gene. When two genes were combined, the most predictive gene set in the evaluation dataset was ATR and PRKCB when linear discriminant analysis was applied.
Conclusions  Combined biomarkers showed good performance in predicting the risk of AD. The constructed predictive nomogram using combined biomarkers could easily be used by clinicians to identify high-risk individuals so that more efficient trials could be designed to reduce the incidence of AD.

Alzheimer’s disease; Risk prediction; Gene expression; Combined biomarker; Machine learning.

Individuals with developmental disorders exhibit a broad spectrum of aggressive behaviors, including self-directed actions and those directed toward others. These behaviors can lead to physical harm, disruptions in daily life, caregiver stress, and an increased risk for abuse and institutionalization. An integrated and multidisciplinary approach, including psychosocial approaches and pharmacotherapy, has been attempted to treat self-injurious and aggressive behaviors, but has shown limited effectiveness in reducing those behaviors. Recently, the use of electroconvulsive therapy has increased as an alternative treatment for pediatric and adolescent patients with treatment-resistant behavior problems in developmental disorders. This review elucidates the indications and clinical effectiveness of electroconvulsive therapy in the management of self-injurious behavior and catatonia in patients with developmental disorders such as autism spectrum disorders and intellectual disabilities.

Neurodevelopmental disorder; Self-injurious behavior; Intellectual disabilities; Autism spectrum disorder; Catatonia; Electroconvulsive therapy.

A conceptual summary of recent trends in the use of electroconvulsive therapy (ECT) for treatment-resistant behavioral problems associated with developmental disorders was provided in the previous review, and this review offers information needed for clinical practice. As it is essentially impossible to obtain evidence-based data in this regard, we have attempted to present a review of practical issues related to the implementation of ECT, such as the public perception by the media, and ethical issues where the target population may include children and adolescents. In addition, we described the assessment tools required for the symptom identification to be treated and the evaluation of symptom changes in response to treatment, which are necessary for determining whether ECT is valid even in treatment-resistant conditions. In order to complement the direct clinical experience of ECT practitioners needed to assess the appropriateness of the currently administered treatment, case reports from other countries were introduced to illustrate the ECT course in each case. To this end, the issues related to the practical process of safe and effective ECT have been summarized in relatively specific detail.

Developmental disorder; Self-injurious behavior; Catatonia; Intellectual disabilities; Autism spectrum disorder; Electroconvulsive therapy.

Cannabis, presently being one of the most commonly employed psychoactive agents globally, ranks after alcohol and nicotine. Despite the permissibility of employing cannabis for medicinal objectives in Korea, the discussion regarding the authorization and control of cannabis for both recreational and medicinal intentions persists, giving rise to apprehensions about the plausible hazards and repercussions of cannabis on public well-being and health. Cannabis has the potential to induce positive experiences that mitigate certain psychiatric symptoms depending on the individual. However, a multitude of studies have demonstrated a close association between cannabis usage and detrimental effects on the brain, including the onset of schizophrenia and the deterioration of cognitive function. The endocannabinoid (eCB) system, which serves as the primary target for the active components of cannabis, was only recently discovered, and the precise mechanisms through which the intricate substances within cannabis interact with the body remain inadequately comprehended. The use of medical cannabis for mental illness has shown promise in treating anxiety, post-traumatic stress disorder, sleep disorders, and substance use disorders. Recent research has focused on the discovery of the eCB system, which plays a role in the therapeutic effects of cannabinoids. These studies are advancing the development of new treatments for mental disorders through research and clinical trials. In conclusion, while cannabis-related substances carry a risk for mental health, the eCB system also holds potential as a new therapeutic mechanism. Further research is needed to better understand the mechanisms of cannabinoids and determine appropriate medical uses.

Cannabis; Medical cannabis; Cannabis legalization; Drug safety; Cannabinoids; Cannabidiol.

Objectives  This study explores knowledge of and attitudes toward electroconvulsive therapy (ECT) among psychiatrists in Korea.
Methods  We emailed questionnaires to psychiatrists to assess their knowledge of and attitudes toward ECT. The present analysis focuses on responses to Lutchman’s questionnaire.
Results  A total of 293 psychiatrists (260 specialists and 33 residents) responded to the questionnaire. The responses showed positive attitudes towards ECT, with an average approval rating of 77.68%. There were no differences between genders, or between specialists and residents, in knowledge of and attitudes toward ECT. However, psychiatrists generally reported insufficient knowledge and/or negative attitudes toward techniques, methods, side effects, and other factors related to clinical implementation of ECT, as well as a lack of clinical experience. In addition, responses were influenced by personal views.
Conclusions  We assume that insufficient knowledge, lack of experience with the advanced technologies and methods of modern ECT, and negative perceptions of side effects limit the use of ECT for treating mental disorders. Further research aimed at improving knowledge of and attitudes toward ECT among psychiatrists is needed to enhance therapeutic efficacy in the treatment of mental disorders.

Electroconvulsive therapy; Psychiatric specialists; Survey of knowledge and attitudes.

Objectives  ZCognitive intervention treatment is known to be effective among dementia patients. To establish an effective nonpharmacological treatment for dementia patients, it is necessary to study how it affects not only cognitive function but also emotional function as well as daily life abilities. This study examined the effects of a cognitive intervention program using the robot PIO.
Methods  The robot-mediated cognitive intervention using “laughter-PIO” was applied to 36 participants rated Clinical Dementia Rating 0.5 or 1. The cognitive function, emotional state, and daily life abilities were evaluated before and after the program.
Results  After the cognitive intervention, the Geriatric Depression Scale-Korean score improved from 11.6 ± 6.3 to 9.0 ± 6.0 (p = 0.03). The subtests of the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet, J2 Boston Name test, J3 Mini-Mental State Exam, and J7 Word Recognition test, showed significant improvements (p < 0.05). The Digit Span Test result increased from 13.1 ± 5.4 to 15.2 ± 6.1 after the program (p < 0.05).
Conclusions  The cognitive intervention program using the robot “PIO” improved cognitive function and the emotional state of dementia patients, and daily life abilities.

Robot; Cognitive intervention program; Cognition; Emotion; Dementia.

Wernicke’s encephalopathy is a life-threatening central nervous system disease caused by thiamine deficiency. Emergent diagnosis is crucial but is frequently underdiagnosed. If Wernicke’s encephalopathy is concomitant with underlying psychiatric disorders, the progression of symptoms becomes less discernible. This can present challenges for clinicians in establishing definitive diagnoses. Frequent problematic drinking and chronic thiamine deficiency have been reported in the homeless population. Clinicians should consider the possibility of developing Wernicke’s encephalopathy in this population. This case report describes a 43-years-old homeless patient with Wernicke’s encephalopathy presented with psychiatric symptoms.

Wernicke encephalopathy; Ill-housed persons; Psychotic disorders.

Objectives : In regard to the social competition hypothesis, depression is viewed as an involuntary defeat strategy. A previous study has demonstrated that adaptation in microenvironments can result in a wide range of behavioural patterns including defense activation disorders. Using a simulation model with evolutionary ecological agents, we explore how the fitness of various defence activation traits has changed over time in different environments with high and low social mobility.

Methods : The Evolutionary Ecological Model of Defence Activation Disorder, which is based on the Marginal Value Theorem, was used to examine changes in relative fitness for individuals with defensive activation disorders after adjusting for social mobility.

Results : Our study examined the effects of social mobility on fitness by varying the d-values, a measure of depression in the model. With a decline in social mobility, the level of fitness of individuals with high levels of defense activation decreased. We gained insight into the evolutionary influence of varying levels of social mobility on individuals' degrees of depression. In the context of a highly stratified society, the results support a mismatch hypothesis which states that high levels of defence are detrimental.

Conclusions : Despite the fact that niche specialization in habitats composed of multiple microenvironments can result in diverse levels of defensive activation being evolutionary strategies for stability, decreased social mobility may lead to a decrease in fitness of individuals with highly activated defence modules. There may be a reason behind the epidemic of depression in modern society.

Evolutionary ecology;Social mobility;Defence activation disorder;Agent-based simulation.

Objectives : Sleep is fundamental to maintaining homeostatic control and has behavioral and psychological effects on humans. To better understand the function and pathophysiology of sleep, specific gene expressions in reference to sleep deprivation have been studied. In this study, we investigated the gene expression of peripheral blood mononuclear cells after sleep deprivation to better understand the functional consequence of sleep.

Methods : In eight healthy men, 24 h sleep deprivation was induced. Blood was sampled at 14:00, before and after sleep deprivation. mRNA was isolated and analyzed via microarrays. cDNAs before and after sleep deprivation were coupled to Cy3 or Cy5, respectively, and normalized cDNAs were selected with a ratio greater than two as a significant gene. Results are expressed as mean.

Results : Among 41174 transcripts, 38852 genes were selected as reliable, and only a small minority (< 1%) of the genes were up-or down-regulated. Total six and eleven genes were selected as significant upregulated and downregulated genes, respectively. Protein tyrosine phosphatase receptor type O was most upregulated (6.9-fold), and low-density lipoprotein receptor-related protein 5-like protein showed the most substantial inhibition (0.06-fold).

Conclusions : This study showed significant associations between sleep deprivation and the immune system. Acute sleep deprivation affects pathways in proinflammatory cytokines as well as metabolic pathways of glutamate and purine, neurotransmitters related to sleep and wake cycle.

Sleep deprivation;Gene expression;Immune system.

Objectives : Maltreatment experiences can alter brain function related to emotion regulation, such as cognitive reappraisal. While dysregulation of emotion is an important risk factor to mental health problems in maltreated people, studies reported alterations in brain networks related to cognitive reappraisal are still lacking.

Methods : Twenty-seven healthy subjects were recruited in this study. The maltreatment experiences and positive reappraisal abilities were measured using the Childhood Trauma Questionnaire-Short Form and the Cognitive Emotion Regulation Questionnaire, respectively. Twelve subjects reported one or more moderate maltreatment experiences. Subjects were re-exposed to pictures after the cognitive reappraisal task using the International Affective Picture System during fMRI scan.

Results : The maltreatment group reported more negative feelings on negative pictures which tried cognitive reappraisal than the no-maltreatment group (p < 0.05). Activities in the right superior marginal gyrus and right middle temporal gyrus were higher in the maltreatment group (uncorrected p < 0.001, cluster size > 20).

Conclusions : We found that paradoxical activities in semantic networks were shown in the victims of maltreatment. Further study might be needed to clarify these aberrant functions in semantic networks related to maltreatment experiences.

Child abuse;Emotion regulation;Semantic network;Functional magnetic resonance imaging.

Objectives : Recently, weight loss has emerged as a national concern in South Korea, and this has resulted in an increase in the frequency of use of central nervous system (CNS)-stimulating appetite suppressants. This study aimed to collect cases of psychotic disorders and bipolar disorders triggered by phentermine and phendimetrazine and explore the clinical features and courses.

Methods : In this retrospective study, we analyzed the electronic medical records of patients and selected eight patients who developed psychotic symptoms and manic symptoms for the first time after taking phentermine and phendimetrazine. All cases were reviewed, and their clinical features and course were summarized.

Results : All eight patients developed psychotic symptoms, and one had accompanying manic symptoms. The final diagnosis was appetite-suppressant-induced psychotic disorder in four patients, schizophrenia in three, and appetite-suppressant-induced bipolar disorder in one. In addition, three patients were diagnosed as having substance-use disorder. The key psychotic symptoms of these patients were hallucinations and paranoia.

Conclusions : These case findings suggest that phentermine and phendimetrazine can cause psychotic disorder, bipolar disorder, or substance use disorder and that medical professionals and the public should practice caution when prescribing and using these drugs.

Substance-induced psychoses;Substance-related disorders;Phentermine;Phendimetrazine.

Objectives : The early growth response 3 (EGR3) gene located in chromosome 8p21.3 is one of the susceptibility loci in many psychiatric disorders. EGR3 gene plays critical roles in signal transduction in the brain, which is involved in neuronal plasticity, neuronal development, learning, memory, and circadian rhythms. Recent studies have suggested EGR3 as a potential susceptibility gene for bipolar disorder (BPD). However, this requires further replication with an independent sample set.

Methods : To investigate the genetic role of EGR3 in Korean patients, we genotyped six single-nucleotide polymorphisms (SNPs) in the chromosome region of EGR3 in 1076 Korean BPD patients and 773 healthy control subjects.

Results : Among the six examined SNPs of EGR3 (rs17088531, rs1996147, rs3750192, rs35201266, rs7009708, rs1008949), SNP rs35201266, rs7009708, rs1008949 showed a significant association with BPD (p = 0.0041 for rs35201266 and BPD2, p = 0.0074 for rs1008949 and BPD, p = 0.0052 for rs1008949 and BPD1), which withstand multiple testing correction. In addition, the 'G-C-C-C' and 'G-C-G-C' haplotypes of EGR3 were overrepresented in the patients with BPD (p = 0.0055, < 0.0001, respectively) and the 'G-T-G-C' haplotype of EGR3 was underrepresented in patients with BPD (p = 0.0040).

Conclusions : In summary, our study supports the association of EGR3 with BPD in Korean population sample, and EGR3 could be suggested as a compelling susceptibility gene in BPD.

Bipolar disorder;Early growth response 3.

Objectives : This study aims to assess the status quo of depression among Korean physicians and identify stressors and psychiatric assets related to it.

Methods : The questionnaire was designed to assess depression, stressors, burnout and psychiatric assets. 343 physicians were included in the analyses.

Results : Physician depression in Korea was found to be related to several daily life stressors and occupational stressors. It was also related to higher burnout and lower psychological assets. Physicians who reported workplace problems, familial problems, and mannerism were at higher risk of depression while who reported passion (in psychiatric assets) were at lower risk of depression.

Conclusions : This study identified factors affecting physician depression in Korea. Further research would benefit physicians and their patients by identifying and testing various, including personal and organizational, intervention methods.

Physician;Depression;Stressors;Psychological assets.

Objectives : Many studies have reported noticeable increases in the proportion of employees working either relatively short or relatively long hours. Such trends have been accompanied by an increasing concern that how much subjective mental well-being of employees would be influenced by their hours of work. The aim of this study was to investigate the association between work hours and clinically relevant depressive symptoms with demographic variables adjusted.

Methods : Participants were employees of a total of 56 private companies and local government organizations in Korea, aged 19 to 65 years. A self-report questionnaire that included items on working hour, job stress, levels of depression, and socio-demographic factors was administered to 15360 Korean employees, with 14477 valid responses. Hierarchical linear regression analyses, adjusted for sociodemographic factors, job related demographic factors, job stress, were used additionally to estimate the association between working hours and depressive scores.

Results : We found that working more than 40 hours per week correlated positively with the level of depressive symptoms after adjusting for demographic variables and the level of job stress. Furthermore, working 40 or fewer hours per week correlated negatively with the level of depressive symptoms. Being younger (β = -0.078, β = -0.099), being a female (β = 2.770, β = 1.268), and possessing a lower level of education (β = -0.315, β = -1.125) were significantly associated with higher level of depressive symptoms in all respondents.

Conclusions : Both of working excessively long or short hours is significantly associated with the prevalence of depressive symptoms. Establishing proper office hours for employees is critical to improving the quality of working conditions and maintaining good mental health in the workplace.

Depression;Occupational health;Occupational stress;Workload;Mental health.

Pharmacogenetics is opening a new era of precision medicine in psychiatry. Drug-metabolizing enzymes are characterized by genetic polymorphisms, which render a large portion of variability in individual drug metabolism. Dose adjustment based on pharmacogenetics knowledge is a first step to translate pharmacogenetics into clinical practice. However, diverse factors including cost-effectiveness should be addressed to provide clinical recommendation. To address current challenges in pharmacogenetics testing in psychiatry, this review provides an update regarding genotyping (SNP analysis, array, and next-generation sequencing), genotype-phenotype correlations, and cost-effectiveness. The current updates on pharmacogenetics in psychiatry will provide guidance for both clinician and researchers to have a consensus in harmonizing efforts to advance the pharmacogenetics field in a part of precision medicine in psychiatry.

Pharmacogenetics;Drug-metabolizing enzyme;CYP450;Genotyping;Psychiatry.

Considering that the aged population increases and the mobility problem is pointed out as a factor that indisposes the quality of life, cognition, and mood, it is important to understand and evaluate the elderly's mobility. Factors that deteriorate mobility in the elderly include physical senility, various health changes including chronic diseases, polypharmacy as well as anticholinergics. Common mobility problems in old age are reduced gait speed, increased gait variability in walking length, careless walking, and frequent falls. Several studies have reported that decreased mobility and deterioration of gait can predict cognitive decline and emotional problems. Aerobic exercise, resistance exercise, and balance exercise are suggested as therapeutic interventions for mobility problems. Active correction for factors that reduce mobility in the elderly and prescribing physical activity can conserve the elderly's quality of life and help improve cognition and mood. There is a need for related research in the future.

Aged;Gait;Accidental falls;Cognition;Mood.

Objectives : Despite growing attention to anxiety in bipolar disorder (BD), little research has assessed anxiety symptoms in the course of BD. The current prospective follow-up study examines the influence of subjectively and objectively measured anxiety symptoms on the course of BD.

Methods : A total of 49 patients with BD were followed-up prospectively for average of one year at an average of four months interval. The Korean version of the Beck Anxiety Inventory (K-BAI), the Hamilton Anxiety Rating Scale, heart rate variability (HRV) were used to measure anxiety subjectively, objectively and physiologically. Participants were divided into high and low anxiety groups based on their K-BAI scores. Kaplan-Meier survival analysis was performed to compare the recurrence of mood episode, suicide attempt, emergency room visit, and psychiatric hospitalization between two groups. Mediators were investigated with Cox proportional hazards models.

Results : Compared to the low anxiety group, the high anxiety group reported significantly higher impulsiveness (p = 0.016) and lower high frequency component on HRV (p = 0.007) after controlling for severity of BD. Regarding survival analysis, the high anxiety group showed hastened depressive episode recurrence (p = 0.048) and suicidal ideation was the mediator of the hazard ratio (HR) 1.089 (p = 0.029) in the Cox model. Moreover, the high anxiety group showed a tendency of accelerated suicide attempt (p = 0.12) and impulsivity was the risk factor of suicide attempt (HR = 1.089, p = 0.036).

Conclusions : This interim analysis of prospective study suggests that high anxiety level in BD may anticipate unfavorable course. Further studies are needed to understand the multifactorial mechanism of anxious bipolar patients.

Anxiety;Bipolar disorder;Prospective follow-up study;Heart rate variability;Depressive episode recurrence.

Fear conditioning and extinction, which are adaptive processes to learn and avoid potential threats, have essential roles in the pathophysiology of anxiety disorders. Experimental fear conditioning and extinction have been used to identify the mechanism of fear and anxiety in humans. However, the brain-based mechanisms of fear conditioning and extinction are yet to be established. In the current review, we summarized the results of neuroimaging studies that examined the brain changes-functional activity and structures-regarding fear conditioning or extinction in healthy individuals. The functional activity of the amygdala, insula, anterior cingulate gyrus, ventromedial prefrontal cortex, and hippocampus changed dynamically with both fear conditioning and extinction. This review may provide an up-to-date summary that may broaden our understanding of pathophysiological mechanisms of anxiety disorder. In addition, the brain regions that are involved in the fear conditioning and extinction may be considered as potential treatment targets in the future studies.

Fear conditioning;Fear extinction;Functional magnetic resonance imaging;Functional activity;Amygdala.

Suicide is a leading cause of death worldwide, especially among adolescents and young adults. Considering this fact, it is imperative that we understand the neural mechanisms underlying suicidal thoughts and behaviors in youth from a neurodevelopmental perspective. In this review, we focused on the magnetic resonance imaging studies that examined the neural correlates of suicidal ideations (SI) or attempts (SA) in youth. We reviewed twenty-three cross-sectional studies reporting the structural and functional alterations in association with SI or SA among adolescents and young adults with various mental disorders. The previous literature suggests that the dorsolateral prefrontal cortex, anterior cingulate cortex, and ventral frontolimbic circuit, may play an important role in the pathophysiology of suicidal behavior in youth through altered top-down control over emotion and impulsivity. Future studies with a longitudinal design and using multimodal imaging techniques may be of help to identify novel therapeutic targets specific for youth with suicidal thoughts and behaviors.

Youth;Suicide;Suicidal behaviors;Brain mechanisms;Magnetic resonance imaging.

Objectives : Clozapine is the most effective atypical antipsychotic agent for the treatment-resistant schizophrenia (TRS), however, only 40%–70% of TRS patients respond to clozapine. Moreover, TRS encompasses various symptom dimensions. Therefore, augmentation with other medications for clozapine is frequently applied. However, the prescription pattern of clozapine and combined medications in Korea is yet to be examined. This study aims to investigate the maintenance treatment pattern of clozapine and augmentation agents in one Korean tertiary hospital.

Methods : The patients with schizophrenia spectrum disorders under clozapine maintenance, defined as one-year clozapine continuation, were subjected for analysis. Medication data at one-year time-point after clozapine initiation was extracted and analyzed.

Results : Among total 2897 patients having clozapine prescription experience from January 2000 to December 2018, 1011 patients were on clozapine maintenance. The mean age of clozapine initiation was 30.2 ± 11.3 years, and the maintenance dose of clozapine was 217.8 ± 124.3 mg/day. Combination rate of antipsychotics, mood stabilizers, and antidepressants were 43.5%, 25.3%, 38.6%, respectively. Most frequently prescribed drugs in each category were aripiprazole, valproate, and sertraline. Olanzapine equivalent dose of combined antipsychotics was 10.4 ± 7.7 mg/day. Male patients were prescribed higher dose of combined antipsychotics and higher rate of antidepressants. Female patients had later onset of clozapine prescription. Patients with two or more combined antipsychotics were prescribed higher dose of clozapine and higher rate of antidepressants compared to patients with one combined antipsychotic.

Conclusions : Taken together, among the patients taking clozapine, a substantial rate of patients were under polypharmacy. The present findings based on the real-world prescription pattern could provide the valuable clinical information on the treatment of TRS-related conditions.

Schizophrenia;Clozapine;Antipsychotic;Polypharmacy.

Objectives : The aim of this study was to examine the association between the sleep pattern, chronotype (midpoint of sleep on free days) and the depressive symptoms in adults aged 19 years and over in Korea. This study also investigated the mediating effect of perceived usual stress (PUS) and self-rated health (SRH) on the association between chronotype and depressive symptoms.

Methods : Among the subjects of the 7th Korea National Health and Nutrition Examination Survey (KNHANES) 2016 and 2018, 16142 adults aged 19 or over responded to the survey and finally 8604 were analyzed according to the exclusion conditions. Logistic regression analysis was conducted to see the risk of depressive symptoms, suicidal ideation over sleep pattern, chronotype. Finally, mediation analysis was performed in order to clarify how PUS and SRH are associated to chronoytpe and depression.

Results : After controlling for potential covariates, weekly sleep duration < 5 hours, ≥ 10 hours was associated with depressive symptoms. And late bed time sleeping after am 1:00 and later midpoints of sleep was associated with a higher level of depressive symptoms. Additionally, the PUS and SRH between chronotype and depressive symptoms showed a serial multiple mediation effect.

Conclusions : Short or long sleep duration, late bed time and later midpoints of sleep on free days are associated with depressive symptoms. Furthermore, the mechanism between chronotype and depressive symptoms needs to be further clarified by identifying the serial multiple mediation effects of PUS and SRH.

Sleep pattern;Chronotype;Depressive symptoms;Perceived usual stress;Self-rated health;Korea National Health and Nutrition Examination Survey.

Objectives : Our study aimed to present the distinctive correlates of formal thought disorder in patients with schizophrenia, using the Clinical Language Disorder Rating Scale (CLANG).

Methods : We compared clinical characteristics between schizophrenia patients with (n = 84) and without (n = 82) formal thought disorder. Psychometric scales including the CLANG, the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale (YMRS), the Calgery Depression Scale for Schizophrenia (CDSS) and the Word Fluency Test (WFT) were used.

Results : After adjusting the effects of age, sex and total scores on the BPRS, YMRS and WFT, the subjects with disorganized speech presented significantly higher score on the abnormal syntax (p = 0.009), lack of semantic association (p = 0.005), discourse failure (p < 0.0001), pragmatics disorder (p = 0.001), dysarthria (p < 0.0001), and paraphasic error (p = 0.005) items than those without formal thought disorder. With defining the mentioned item scores as covariates, binary logistic regression model predicted that discourse failure (adjusted odds ratio [aOR] = 5.88, p < 0.0001) and pragmatics disorder (aOR = 2.17, p = 0.04) were distinctive correlates of formal thought disorder in patients with schizophrenia.

Conclusions : This study conducted Clinician Rated Dimensions of Psychosis Symptom Severity (CRDPSS) and CLANG scales on 166 hospitalized schizophrenia patients to explore the sub-items of the CLANG scale independently related to formal thought disorders in schizophrenia patients. Discourse failure and pragmatics disorder might be used as the distinctive indexes for formal thought disorder in patients with schizophrenia.

Clinical Language Disorder Rating Scale;Discourse failure;Formal thought disorder;Pragmatics disorder;Schizophrenia.

Objectives : In electroconvulsive therapy (ECT) research and practice, the precise determination of seizure duration is important in the evaluation of clinical relevance of the ECT-induced seizure. In this study, we have developed computerized algorithms to assess the duration of ECT-induced seizure.

Methods : Subjects included 5 males and 6 females, with the mean age of 33.1 years. Total 55 ECT sessions were included in the analysis. We analyzed the standard deviation of a finite block of electroencephalography (EEG) data and the change in the local slope of RR intervals in electrocardiography (ECG) signals during ECT-induced seizure. And then, we compared the calculated seizure durations from EEG recording (EEG algorithm) and ECG recording (ECG algorithm) with values determined by consensus of clinicians based on the recorded EEG (EEG consensus), as a gold standard criterion, in order to testify the computational validity of our algorithms.

Results : The mean seizure durations calculated by each method were not significantly different in sessions with abrupt flattened postictal suppression and in sessions with non-abrupt flattened postictal suppression. The intraclass correlation coefficients (95% confidence interval) of the three methods (EEG algorithm, ECG algorithm, EEG consensus) were significant in the total sessions [0.79 (0.70-0.86)], the abrupt flattened postictal suppression sessions [0.84 (0.74-0.91)], and the non-abrupt flattened postictal suppression sessions [0.67 (0.45-0.84)]. Correlations between three methods were also statistically significant, regardless of abruptness of transition.

Conclusions : Our proposed algorithms could reliably measure the duration of ECT-induced seizure, even in sessions with non-abrupt transitions to flat postictal suppression, in which it is typically difficult to determine the seizure duration.

Electroconvulsive therapy;Electrocardiography;Electroencephalography;Postictal suppression;Seizure duration.

Objectives : The purpose of this study is to investigate the interest level, perception and attitude of suicide high-risk group toward the media's suicide report, and also to provide the fundamental data in order to strengthen both the standard and the recommendation of media coverage in Korea.

Methods : We analyzed the data from the 2013 The Korea National Suicide Survey. The study included 1500 participants aged between 19 and 75 years. The participants were selected through the regional multi-layer stratification method using the sampling frame of the 2010 Census. One-on-one face-to-face interviews investigated the interest level, opinions, and attitudes toward suicide reports and collected data on past suicide history and demographic data. The collected data were evaluated using multiple logistic regression analysis. A probability level of p < 0.05 was considered statistically significant.

Results : The suicide high risk groups with histories of suicidal ideations or attempts showed more interest in suicidal reports [suicidal thought odds ratio (OR) = 1.81, 95% confidence interval (CI) = 1.40-2.34 ; suicidal attempt OR = 3.21, 95% Cl = 1.52-6.78]. However, there was no difference among the groups in thought that suicide reports incite suicide (suicidal thought OR = 1.26, 95% Cl = 0.92-1.73 ; suicidal attempt OR = 0.96, 95% Cl = 0.44-2.09). The suicide high risk groups showed a positive attitude toward suicide reports, but it was not statistically significant (suicidal thought OR = 1.10, 95% Cl = 0.41-2.92 ; suicidal attempt OR = 1.10, 95% Cl = 0.76-1.59).

Conclusions : We suggest the need of careful attitude of media suicidal reports not to bring about copycat suicides. and also we offer suicide prevention campaign based on media leverage.

Suicide;Media;Suicidal thoughts;Suicide attempts;Attitudes.

Objectives : The aim was to find effective vectorization and classification models to predict a psychiatric diagnosis from text-based medical records.

Methods : Electronic medical records (n = 494) of present illness were collected retrospectively in inpatient admission notes with three diagnoses of major depressive disorder, type 1 bipolar disorder, and schizophrenia. Data were split into 400 training data and 94 independent validation data. Data were vectorized by two different models such as term frequency-inverse document frequency (TF-IDF) and Doc2vec. Machine learning models for classification including stochastic gradient descent, logistic regression, support vector classification, and deep learning (DL) were applied to predict three psychiatric diagnoses. Five-fold cross-validation was used to find an effective model. Metrics such as accuracy, precision, recall, and F1-score were measured for comparison between the models.

Results : Five-fold cross-validation in training data showed DL model with Doc2vec was the most effective model to predict the diagnosis (accuracy = 0.87, F1-score = 0.87). However, these metrics have been reduced in independent test data set with final working DL models (accuracy = 0.79, F1-score = 0.79), while the model of logistic regression and support vector machine with Doc2vec showed slightly better performance (accuracy = 0.80, F1-score = 0.80) than the DL models with Doc2vec and others with TF-IDF.

Conclusions : The current results suggest that the vectorization may have more impact on the performance of classification than the machine learning model. However, data set had a number of limitations including small sample size, imbalance among the category, and its generalizability. With this regard, the need for research with multi-sites and large samples is suggested to improve the machine learning models.

Text-classification;Electronic medical record;Vectorization;Machine learning;Present illness;Psychiatric diagnosis.

Objectives : Ketamine has been reported to have antidepressant effects or psychotomimetic effects. The aim of this study was to investigate the behavioral effects of ketamine treatment at various sub-anesthetic doses in adolescent and adult naïve mice.

Methods : In each experiment for adolescent and adult mice, a total of 60 male Institute of Cancer Research mice were randomly divided into 6 groups, which were intraperitoneally treated with physiological saline, 10, 20, 30, 40, and 50 mg/kg ketamine for consecutive 3 days. At 1 day after last injection, the locomotor and depressive-like behaviors were evaluated in mice, using open field test (OFT) and forced swim test (FST), respectively.

Results : In case of adolescent mice, ketamine dose was negatively correlated with total distance traveled in the OFT (Spearman's rho = -0.27, p = 0.039). In case of adult mice, we found significant positive correlation between ketamine dose and duration of immobility in the FST (Spearman's rho = 0.45, p < 0.001). Immobility time in the 50 mg/kg ketamine-treated mice was significantly higher compared to the saline-treated mice (Dunnett's post-hoc test, p = 0.012).

Conclusions : We found that the repeated treatment with ketamine could decrease the locomotor or prolong the duration of immobility in mice as the dose of ketamine increased. Our findings suggest that sub-anesthetic doses of ketamine might induce schizophrenia-like negative symptoms but not antidepressant effects in naïve laboratory animals.

Ketamine;Mouse;Open field test;Forced swim test.

Modified electroconvulsive therapy (ECT) which started in 1950s is a safe and efficacious treatment for several mental disorders including mood disorders and psychotic disorders. However, its usage in present days is still limited by misconceptions and stigmata of ECT. This paper overviews the background from which the stigmata of ECT stemmed and the current status of stigmata surrounding ECT among the public and medical professionals. In addition, a few potential strategies for reducing stigmata of ECT are provided in this review.

Electroconvulsive therapy;Stigma;History.

Electroconvulsive therapy (ECT) is indicated for various mental disorders (e.g., major depressive disorder, schizophrenia, and bipolar disorder) and the behavioral and psychological symptoms of dementia in elderly patients. Furthermore, ECT is a useful first-line treatment in emergency and crisis situations such as suicide risk, violent behavior, catatonia, and food refusal, which are more frequent in elderly patients. ECT is also effective in the treatment of the motor symptoms of neurological disorders, such as Parkinson's disease and Huntington's disease. Due to the high risk of various physical diseases, the comorbid physical conditions of elderly patients should be individually controlled to optimize ECT treatment. Compared to young adults, in elderly patients the seizure threshold is higher, the seizure duration is shorter, and the anesthetic dose is lower. On the contrary, the response rate in the elderly is both faster and higher. Considering potential cognitive decline and the prevention of further deterioration of cognitive function in elderly patients, in the absence of significant comorbidities, twice weekly sessions and right unilateral electrode placement with a lower seizure threshold and less cognitive effect are preferred to bilateral electrode placement, which has a high risk of adverse cognitive effects. After an acute course of ECT, continuation and maintenance of ECT, combined with prescription of therapeutic drugs, may prevent possible relapse or recurrence of mental disorders. In conclusion, ECT can be used to treat mental disorders in elderly adults, with safety and effectiveness comparable to that in young adults.

Mental disorder;Elderly;Electroconvulsive therapy.

Depressive disorder is a very common disease, clinical manifestations vary, and the mechanism is not clear. Therefore, a pharmacotherapy is very important to achieve sufficient therapeutic effect, but the choice of drug is not easy due to the occurrence of side effects of treatment and confusion with clinical features. It is easy to overlook the side effects of weight gain with antidepressants compared with antipsychotics, but they are frequently observed in clinical settings. The first-generation antidepressants have higher weight gains than selective serotonin reuptake inhibitors. Serotonin norepinephrine reuptake inhibitors are observed to have less weight gain, and dopamine norepinephrine reuptake inhibitors have weight loss effect due to decreased appetite. Mirtazapine, an atypical antidepressant, has a strong histamine H1 blockade, and gains weight gain from short-term use. The effects of desvenlafaxine, vortioxetine, and agomelatin on weight, which have recently been increasing in use, have not been largely identified. For better compliance, studies on weight gain due to the use of antidepressants are needed.

Depressive disorder;Weight gain;Drug therapy.

Suicidality is the most serious complication of mood disorders and psychosis; effective treatment should reduce suicide rates. The Organization for Economic Cooperation and Development age-standardized suicide rate in Korea was 22.6 in 2018, much higher compared to other countries worldwide. As mental and psychiatric problems are the main reasons for suicide attempts, accounting for 31.6% in 2018, targeting such problems should be the focus of efforts to reduce suicide rates. However, the ability of current pharmacotherapeutic and psychotherapeutic interventions to reduce suicide rates is limited due to their delayed effects. Therefore, electroconvulsive therapy (ECT) has been proposed as an alternative treatment. This approach is effective for treating most mental disorders associated with high suicide rates, including severe depression, bipolar disorder, and intractable psychotic disorders; ECT is also effective for Parkinson's disease, which has the highest suicide rate among all disorders in Korea. The acute, long-term, and prophylactic effects of ECT on suicidality have been reported in the literature, and treatment guidelines outside of Korea recommend that ECT be used at an early stage for rapid reduction of suicide rates, as opposed to being applied as a treatment of last resort. However, only ~0.092 of every 10000 members of the Korean general population received ECT in 2018; this is much lower than the average rate worldwide, of 2.2 per 10000. Elimination of obstacles to the use of ECT, early crisis intervention involving administration of ECT for rapid stabilization, and maintenance ECT to prevent recurrence should reduce suicide rates.

Mental health;Crisis intervention;Suicidality;Electroconvulsive therapy.

Objectives : Psychological resilience plays a significant role in many aspects of mental health. The aim of this study was to find an association between childhood attention deficit hyperactivity disorder (ADHD) features and adulthood psychological resilience in patients with mood disorders.

Methods : A total of 213 patients with mood disorders including major depressive disorder or bipolar I, II disorder and 909 healthy controls were included. We assessed childhood ADHD features using the Wender Utah Rating Scale (WURS), adulthood psychological resilience using the Connor-Davidson Resilience Scale (CD-RISC), and current depressive mood using the Beck Depression Inventory (BDI). Pearson's correlation, multiple linear regression and a mediation analyses were performed to examine the relationships between three WURS factor (impulsivity, inattention, and mood instability) scores, the BDI score, and the CD-RISC score.

Results : The CD-RISC score was negatively correlated with the WURS childhood inattention factor score and current BDI score in patients with mood disorders. BDI score mediated the influence of the inattention factor score on CD-RISC score among patients with mood disorders. The CD-RISC score was significantly lower in patients with mood disorders than in controls even after controlling for age, WURS scores, and the BDI score.

Conclusions : An evaluation of psychological resilience is important for enhancing recovery and quality of life in patients with mood disorders. When assessing psychological resilience, current depression and ADHD features in childhood, particularly inattention, should be considered.

Psychological resilience;Attention deficit hyperactivity disorder;Bipolar disorder;Major depressive disorder;Mood disorder.

Objectives : The purpose of the present study was to examine the relationship between the chronotype and the burnout, so we investigated the mediating effects of the mediators such as perceived stress, stress response, and depression.

Methods : Employees working at Incheon Customs conducted a mental health self-examination through the internet. Among them, 174 people who agreed to the mental health survey participated in the study. Participants completed questionnaires including Composite Scale of Morningness (CSM), Center for Epidemiological Studies-Depression Scale (CES-D), Perceived Stress Scale (PSS), Stress Response Inventory (SRI), Maslach Burnout Inventory-General Survey (MBI-GS).

Results : Our results showed a higher degree of CES-D, SRI, exhaustion, and cynicism in evening and intermediate type compared to morning type, and a higher degree of professional efficacy in morning type compared to intermediate type. CSM was shown to have a direct effect on exhaustion and indirect effect through CES-D and SRI. CSM also had a direct effect on professional efficacy and had an indirect effect through the CES-D. However, CSM was found to have only indirect effects through the SRI for Cynicism.

Conclusions : In this study, individuals with evening type tend to experience a high degree of burnout (exhaustion, cynicism and professional efficacy) through the mediation effect of depression and stress response. Further study is necessary to reveal the effect of management of the depression and stress response in the employee with evening type.

Burnout;Chronotype;Depression;Stress response;Mediation effect study.

Objectives : Amyloid β positron emission tomography (Aβ PET) is widely used as a diagnostic tool in patients who have symptoms of cognitive impairment, however, this diagnostic examination is too expensive. Thus, predicting the positivity of Aβ PET before patients undergo the examination is essential. We aimed to analyze clinical predictors of patients who underwent Aβ PET retrospectively, and to develop a predicting model of Aβ PET positivity.

Methods : 468 patients who underwent Aβ PET with cognitive impairment were recruited and their clinical indicators were analyzed retrospectively. We specified the primary outcome as Aβ PET positivity, and included variables such as age, sex, body mass index, diastolic blood pressure, systolic blood pressure, education, dementia family history, Mini Mental Status Examination (MMSE), Clinical Dementia Rating (CDR), Clinical Dementia Rating-Sum of Box (CDR-SB), hypertension (HTN), diabetes mellitus (DM) and presence of apolipoprotein E (ApoE) E4 as potential predictors. We developed three final models of amyloid positivity prediction for total subjects, mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia using a multivariate stepwise logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) value was calculated for the ROC curve.

Results : Aβ PET negative patients were 49.6% (n = 232), and Aβ PET positive patients were 50.4% (n = 236). In the final model of all subjects, older age, female sex, presence of ApoE E4 and lower MMSE are associated with Aβ PET positivity. The AUC value was 0.296. In the final model of MCI subjects (n = 244), older age and presence of ApoE E4 are associated with Aβ PET positivity. The AUC value was 0.725. In the final model of AD subjects (n = 173), lower MMSE scores, the presence of ApoE E4 and history of HTN are associated with Aβ PET positivity. The AUC value was 0.681.

Conclusions : The cerebral amyloid positivity model, which was based on commonly available clinical indicators, can be useful for prediction of amyloid PET positivity in MCI or AD patients.

Amyloid;Alzheimer’s disease;Mild cognitive impairment;Apolipoprotein E.

Objectives : The aim of this study is to investigate the association between secondhand smoke (SHS) exposure and depressive symptoms among Korean adults. This study also explored the mediating role of self-rated health (SRH) and perceived usual stress (PUS) in the association between depressive symptoms, suicidal ideation and SHS exposure.

Methods : Data from the Korea National Health and Nutrition Examination Surveys (KNHANES) in 2014 and 2016 was analyzed for 10539 participants aged 19 years or older. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in the logistic regression analysis with adjustment for the potential confounding factors. We also adopted the mediation analysis method by Hayes and Preacher.

Results : After adjusting for the potential confounding factors, SHS at home and at public places were associated with depressive symptoms and suicidal ideation among non-smokers. After adjusting for the potential confounding factors, SHS at home and at public places was associated with depressive symptoms and suicidal ideation among non-smokers. Meanwhile SHS at workplaces was associated with depressive symptoms among former smokers and with suicidal ideation among current smokers. There was an additive effect of SHS on depressive symptoms only among non-smokers. SRH mediated the association between SHS and depressive symptoms and suicidal ideation among non-smokers. We did not observe any significant mediating effect of SRH nor PUS on the association between SHS and depressive symptoms among former and current smokers.

Conclusions : SHS may be associated with depressive symptoms and suicidal ideation in Korean adults. Our study elucidated how SHS interacted with depressive symptoms among non-smokers through the mediation by SRH.

Secondhand smoke;Depressive symptoms;Suicidal ideation;Self-rated health;Perceived usual stress;Korea National Health and Nutrition Examination Surveys.

Leucine rich glioma inactivated (LGI1) encephalitis is an uncommon neurological disorder rarely encountered in clinical practice. However, it is a potentially fatal autoimmune syndrome that can decrease the level of consciousness, possibly progressing to coma. Additionally, unless diagnosed and promptly treated, it can cause permanent cognitive impairment. Since LGI1 encephalitis can initially present with psychiatric symptoms, there can be delays in reaching a proper diagnosis. This report describes a case of a 47-year-old woman with LGI1 antibodies-associated limbic encephalitis who initially presented with psychosis. Her blood tests were normal and no MRI and EEG abnormalities were found. Cerebrospinal fluid analysis was negative for other possible infectious causes. Three months after admission, she was found to be LGI1 antibody positive. LGI1 encephalitis should be suspected in patients with symptoms such as memory loss, confusion, seizures, and psychiatric symptoms. Prompt diagnosis and treatment of LGI1 encephalitis are warranted because prognosis becomes worse when such actions are delayed.

LGI1 encephalitis;Autoimmune encephalitis;Bipolar disorder.