Korean Journal of Biological Psychiatry

The digital phenotype refers to the characteristics or patterns defined by the real-time collection, quantification, and analysis of multimodal data encompassing behavioral, physiological, cognitive, emotional, and contextual signals derived from digital devices. This approach leverages passive and active data streams from smartphones and wearable sensors, enabling continuous and ecologically valid monitoring of mental states in naturalistic settings. In recent years, psychiatry has increasingly explored digital phenotypes to support early symptom detection, personalized treatment design, and longitudinal tracking of disease progression. However, the clinical adoption of digital phenotypes necessitates careful consideration of ethical and institutional challenges, including data privacy, the scope and continuity of consent, personal health data management, algorithmic transparency, and disparities in digital access. This paper examines these ethical and institutional issues surrounding the clinical application of digital phenotypes and evaluates complementary strategies, such as dynamic consent frameworks and privacy-preserving data infrastructures, to ensure ethical utilization. Ultimately, the effective integration of digital phenotypes in psychiatric care requires sustained interdisciplinary dialogue and a multilayered, institutional approach grounded in ethical responsibility and patient-centered principles.

Digital phenotyping; Digital health; Mental health; Precision medicine; Ethics.

Compassion has been increasingly recognized as a therapeutic factor in psychological interventions, but its role in biological psychiatry remains less explored. This review examines the neurobiological mechanisms and clinical relevance of compassion within a biological psychiatric framework. Compassion involves neural systems associated with positive affect and prosocial motivation, including the medial prefrontal cortex, nucleus accumbens, and oxytocin-related pathways. It is also linked to increased vagal activity and heart rate variability, indicating enhanced parasympathetic regulation. Compassion-focused therapy and mindful self-compassion have shown benefits in emotion regulation and reductions in self-criticism and post-traumatic stress symptoms. These effects suggest that compassion-based interventions may complement biological treatments, particularly during recovery. Individual differences in response to compassion, including fear or resistance, highlight the need for personalized approaches. Integrating compassion into biological psychiatry may help address emotional and relational aspects of mental illness that are not fully covered by standard treatments. This review outlines current evidence and suggests directions for incorporating compassion-based practices into psychiatric care.

Compassion; Self-compassion; Neurobiology; Biological psychiatry; Heart rate variability.

This narrative review synthesizes functional magnetic resonance imaging (fMRI) evidence on functional connectivity within largescale brain networks implicated in loneliness. Loneliness is a complex neurobiological condition that extends beyond transient emotional states, exerting profound effects on psychological, cognitive, and physical health. It is a significant risk factor for depression, anxiety, suicidal ideation, cognitive decline, reduced quality of life, social dysfunction, and increased all-cause mortality. Neuroimaging evidence indicates that loneliness involves disrupted functional connectivity across large-scale brain networks, suggesting shared, transdiagnostic neural mechanisms. Specifically, we synthesize human fMRI findings to delineate loneliness-related alterations in network-level connectivity and compare these alterations with patterns observed in depression, anxiety, and suicidal ideation. Loneliness is consistently linked to altered functional connectivity across six core systems—sensory circuit, salience network, attention network, default mode network, cognitive control network, and reward circuit. These alterations reflect imbalances in perceptual integration, threat detection, attention regulation, self-referential processing, cognitive control, and social reward sensitivity, and collectively may constitute a shared neural vulnerability across multiple mental health conditions. Loneliness may represent a chronic neurobiological state characterized by pervasive functional dysconnectivity. Characterizing these patterns is critical for advancing transdiagnostic models of mental health vulnerability and for guiding the development of network-targeted interventions for loneliness.

ZLoneliness; Social isolation; Functional connectivity; Large-scale brain networks; Affective neuroscience.

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, with rapidly growing prevalence and socioeconomic burden, particularly in aging societies such as South Korea. The amyloid cascade hypothesis has long emphasized amyloid-β (Aβ) deposition in AD pathogenesis. Many therapeutic strategies targeting Aβ production, aggregation, or clearance—such as active immunization, monoclonal antibodies (bapineuzumab, solanezumab, gantenerumab, crenezumab), and β- or γ-secretase inhibitors—failed to show meaningful clinical benefit or were halted due to safety issues including amyloid-related imaging abnormalities. Despite these setbacks, recent trials of lecanemab and donanemab demonstrated significant slowing of cognitive decline, resulting in FDA approval, with lecanemab also launched in South Korea. New candidates including remternetug, trontinemab, and sabirnetug are under development. This review summarizes the developmental history and lessons learned from anti-amyloid therapies, discusses the significance of recent advances, and considers future directions including early intervention, multi-target strategies, biomarker-based precision approaches, and health-policy implications.

Alzheimer disease; Beta amyloid; Monoclonal antibodies; Amyloid plaques; Lecanemab; Donanemab.

Objectives Schizophrenia is characterized by widespread perceptual impairments, including deficits in basic sensory processing. Mismatch negativity reduction is a robust neurophysiological marker of these deficits. While previous research has focused on lowfrequency abnormalities, this study aimed to investigate gamma-band responses to standard auditory stimuli in patients with schizophrenia, hypothesizing that gamma oscillatory activity would be diminished compared to healthy controls.
Methods A total of 68 patients diagnosed with schizophrenia or schizoaffective disorder and 38 healthy controls participated. Auditory oddball paradigms were administered while electroencephalography data were recorded. Event-related potentials (ERP) and event-related spectral decomposition (ERSD) were conducted to evaluate evoked power, single-trial power and inter-trial coherence (ITC) in response to standard stimuli. Statistical comparisons between groups were performed using t-tests, and multiple regression analyses examined associations between neurophysiological measures and clinical variables.
Results No significant differences were found between groups in P1 latency or amplitude in ERP analyses. However, ERSD revealed that schizophrenia patients exhibited significant reductions in evoked gamma power (t=2.755, p=0.008, d=0.628), single-trial gamma power (t=2.258, p=0.026, d=0.457), and ITC (t=2.151, p=0.036, d=0.507) compared to controls. Multiple regression analyses showed no significant influence of clinical variables on these neurophysiological measures.
Conclusions These findings demonstrate that individuals with schizophrenia show marked reductions in both gamma-band power and phase coherence in response to standard auditory stimuli, suggesting impaired formation of mnemonic templates essential for change detection. Disrupted gamma oscillatory activity may underlie perceptual dysfunctions and contribute to the pathophysiology of schizophrenia. Further research examining cross-frequency coupling and its clinical implications is warranted.

Schizophrenia; Mismatch negativity; Electroencephalography; Gamma rhythm; Auditory perception; Neurophysiology

Objectives The gut–brain axis has been implicated in the pathophysiology of depression. Probiotics, particularly those derived from the infant gut, are emerging as promising psychobiotic agents due to their immunomodulatory and neurochemical properties. This study aimed to compare the psychobiotic potential of different Limosilactobacillus fermentum strains isolated from infant feces in a zebrafish model of unpredictable chronic stress (UCS).
Methods Adult zebrafish were exposed to UCS for 14 days and orally administered one of three Limosilactobacillus fermentum strains (IR51, IM57, IR62) for two weeks following stress exposure. Behavioral assessments were conducted in week 5 using the novel tank test and social preference test. Gut microbiota were analyzed via 16S rRNA sequencing. Gene expression in the telencephalon, and intestinal tissue was assessed by quantitative polymerase chain reaction.
Results Among the tested strains, IR62 most effectively reduced anxiety-like behaviors, evidenced by decreased bottom-dwelling time (IR62=45.55±0.91 sec vs. normal diet [ND]=50.83±0.73 sec, p<0.001) reduced latency to reach the top zone (IR62=38.29±2.00 sec vs. ND=43.25±1.61 sec, p<0.001) and decreased shoal cohesion (IR62=33.82±0.65 sec vs. ND=35.74±1.49 sec, p<0.05). IR62 restored gut microbial β-diversity and selectively increased health-associated genera such as Cetobacterium, while reducing potential pathobionts like Plesiomonas. In the telencephalon, IR62 markedly upregulated bdnf (false discovery rate-adjusted p=0.002), il-10 (p=0.002), and vmat2 (p=0.002). In the intestine, IR62 uniquely enhanced zo1.1 expression (p=0.007), a tight-junction gene critical for barrier integrity. Conclusions L. fermentum IR62 ameliorates anxiety-like behaviors in zebrafish exposed to chronic stress, likely via modulation of gut microbiota and telencephalic neuroimmune pathways. These findings support the therapeutic potential of infant-derived probiotics for gut–brain axis interventions in anxiety disorders.

Unpredictable chronic stress; Zebrafish; Anxiety; Probiotics; Psychobiotics; Infant-derived Limosilactobacillus.