Bipolar disorder (BD) is a highly heritable psychiatric condition characterized by recurrent alternations between manic and depressive episodes. This review summarizes recent advances in understanding the genetic architecture of BD, spanning early heritability and candidate gene studies through genome-wide and sequencing-based discoveries, and discusses the potential clinical implications of these findings.Current concepts: Family and twin studies have established the substantial heritability of BD, whereas early candidate gene approaches focusing on neurotransmitter and circadian pathways demonstrated limited reproducibility. In contrast, large-scale genome-wide association studies have identified numerous common risk variants implicating synaptic signaling, calcium channel function, and neurodevelopmental processes. Complementary exome and whole-genome sequencing studies have further uncovered rare variants and structural alterations contributing to disease risk. Epigenome-wide association studies additionally reveal how genetic variants interact with DNA methylation and chromatin accessibility to regulate transcription. Emerging multi-ancestry research, including studies involving Korean cohorts, has expanded understanding of both shared and population-specific loci. Functionally, BD risk genes converge on biological networks involved in neurotransmission, ion channel regulation, neurodevelopment, circadian rhythm regulation, and immune-inflammatory pathways.Discussion and conclusion: Despite these genomic advances, translation into routine clinical practice remains limited. Integrating genetic findings with multi-omics data and detailed clinical phenotypes may improve diagnostic precision, enhance prediction of treatment response (e.g., lithium efficacy and adverse drug reactions), and support the development of personalized psychiatry. Future research should prioritize cross-ancestry analyses, functional validation, and causal inference frameworks to bridge the gap between genetic discovery and clinical application.

Intracranial hypotension typically presents with orthostatic headache caused by cerebrospinal fluid (CSF) hypovolemia, most commonly resulting from spontaneous or iatrogenic CSF leaks. Traumatic rupture of an occult congenital sacral meningocele following a minor injury is exceptionally rare and may be diagnostically challenging. We report the case of a 40-year-old woman in Korea who developed sudden severe orthostatic headache immediately after a minor coccygeal contusion. Magnetic resonance myelography demonstrated a 5.8-cm dural ectasia/meningocele at the S3 level with a focal CSF fistula extending into the presacral space, accompanied by a tethered cord and an intradural lipoma. Given the anticipated risks associated with definitive surgical repair, a targeted trans-sacrococcygeal epidural blood patch was administered, resulting in substantial symptomatic improvement. This case highlights that while most post-traumatic CSF leaks occur at the cervical or thoracic level, occult spinal dysraphism should be considered a rare predisposing factor in post-traumatic orthostatic headache, particularly when trauma involves the sacrococcygeal region or when standard imaging findings are unrevealing. This finding also suggests that targeted caudal epidural blood patches may serve as a reasonable and less invasive treatment option when surgical intervention carries a high risk.

Olanzapine is a second-generation antipsychotic drug associated with the development of type 2 diabetes. However, the development and remission of diabetes with glutamic acid decarboxylase (GAD) antibody (Ab) positivity related to olanzapine treatment have not been reported. Here, we present the case of a 33-year-old man taking olanzapine who was diagnosed with diabetes with GAD Ab positivity complicated by diabetic ketoacidosis (DKA). After discontinuation of the drug and tight glycemic control, his diabetes remitted, and the GAD Ab became negative spontaneously after 18 months. The classification of diabetes is challenging because of overlapping autoimmune and metabolic features. Olanzapine may have contributed to pancreatic β-cell apoptosis, which could potentially trigger autoimmunity and the development of type 1 diabetes-like features (DKA as the initial presentation, a low C-peptide level, and GAD Ab positivity). The rapid amelioration of hyperglycemia and weight reduction may be responsible for the remission of diabetes after the discontinuation of olanzapine.

Objective: This study aimed to develop a reliable and valid Mixed State Severity Index (MSSI) to assess mood instability in patients with mood disorders and determine cutoff scores. Methods: Twenty-one items were selected based on Koukopoulos’ criteria for mixed depressive episode, historically referred to as agitated depression, and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision mixed features criteria. The MSSI was administered to 242 patients (major depressive disorder [n=92], bipolar disorder [BD] I [n=78], and BD II [n=72]) and 726 controls. Results: The MSSI demonstrated high internal consistency (α=0.78–0.90). Exploratory factor analysis revealed a stable four-factor structure. Based on receiver operating characteristic analysis, optimal cutoff scores were identified to distinguish mood disorder groups from controls, ranging from 19.5 to 27.5 depending on diagnosis. Conclusion The MSSI is a reliable and valid instrument for assessing the severity of mixed features in patients with mood disorders. The established cutoff scores enhance its clinical utility, providing robust diagnosis and treatment planning support.

Background: Observational studies have suggested associations between dietary polyunsaturated fatty acids (PUFAs) and cancer risk; however, causal inference regarding skin cancer remains limited due to potential recall bias, confounding, and reverse causation. Objective: This study aimed to evaluate the causal association between genetically predicted circulating PUFA levels and the risk of skin cancers, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. Methods: We conducted a 2-sample Mendelian randomization (MR) study using genome-wide association study summary statistics from the UK Biobank (PUFAs, n=115,006) and the FinnGen consortium (BCC, n=26,272; SCC, n=4,663; melanoma, n=5,753). Genetic instruments were derived for omega-3, docosahexaenoic acid, omega-6, linoleic acid, and the omega-6:3 ratio.Multiple MR methods—including inverse-variance weighted, MR-Egger, weighted median, weighted mode, and MR-PRESSO—were applied to test for consistency and assess pleiotropy and heterogeneity. Results: A higher genetically predicted linoleic acid to total fatty acid ratio was associated with a significantly lower risk of BCC and SCC. Conversely, higher genetically proxied serum omega-3 levels were associated with increased risks of BCC, SCC, and melanoma. The risk effect on SCC was attenuated upon exclusion of rs174528, a variant in the fatty acid desaturase 1 (FADS1) gene, suggesting a role for endogenous PUFA metabolism in carcinogenesis. Conclusion This MR analysis supports a causal role of circulating PUFAs in skin cancer development and highlights the importance of FADS-mediated endogenous PUFA metabolism. These findings provide novel insights into the genetic and metabolic underpinnings of skin cancer susceptibility.

Psychiatric disorders exhibit complex genetic characteristics such as substantial polygenicity, pleiotropy, and genetic overlap, making them difficult to fully understand through studies focused solely on single genes or individual diseases. This review underscores the importance of multivariate and multi-trait analyses in psychiatric genetics and provides a comprehensive overview of major analytical tools, including their concepts, strengths, limitations, and applications. By addressing the current methodological challenges and proposing future directions, we aim to advance our understanding of the genetic architecture underlying psychiatric disorders and support progress towards precision medicine.

Background: This study investigated the relationship between coronavirus disease 2019 (COVID-19), delirium, and 1-year mortality. Factors associated with delirium in COVID-19 patients were identified, along with the influence of psychotropic medications on delirium. Methods: The study used the South Korean National Health Insurance Service database.Adult COVID-19 patients diagnosed between October 2020 and December 2021 were included, with a propensity score-matched control group. Time-dependent Cox regression assessed associations among COVID-19, delirium, and mortality. Logistic regression analyzed the impact of psychotropic medications on delirium incidence. Results: The study included 832,602 individuals, with 416,301 COVID-19 patients. COVID-19 (hazard ratio [HR], 3.03; 95% confidence interval [CI], 2.92–3.13) and delirium (HR, 2.33;95% CI, 2.06–2.63) were independent risk factors for 1-year mortality. Comorbidities, insurance type, and residence were also related to mortality. Among COVID-19 patients, antipsychotic use was associated with lower delirium incidence (odds ratio [OR], 0.38; 95% CI, 0.30–0.47), while mood stabilizers (OR, 1.77; 95% CI, 1.40–2.21) and benzodiazepines (OR, 8.62; 95% CI, 7.46–9.97) were linked to higher delirium incidence. Conclusion COVID-19 and delirium are risk factors for 1-year mortality. Some factors associated with delirium in COVID-19 patients are modifiable and can be targeted in preventive and therapeutic interventions.

Objectives: In this study, we aimed to compare the genetic architecture of schizophrenia (SCZ) and bipolar disorder (BD) in a Korean population by analyzing polygenic risk scores (PRS) derived from large-scale psychiatric disorder genome-wide association study data, based on genetic information collected from SCZ, BD, and healthy control groups. Methods: The study included 713 Korean patients with SCZ, 1,317 with BD, 526 healthy controls. Genotyping was performed using the Korean Biobank Array. PRS-continuous shrinkage method was used to calculate the PRS. Analysis of covariance (ANCOVA) was conducted to determine the association between SCZ or BD disorder and PRS after adjusting for sex. Results: ANCOVA revealed significant differences in PRS values by diagnosis for PRS for SCZ (F=215.281, p<0.001), PRS for BD (F=13.811, p<0.001), and PRS for major depressive disorder (F=6.042, p=0.002). Post-hoc analysis showed that PRS for SCZ was highest in SCZ, followed by BD, and healthy controls. PRS for BD was elevated in both BD and SCZ compared to healthy controls. Conclusion Our study revealed quantitative differences in genetic architecture between SCZ and BD compared to healthy controls, while also suggesting a shared genetic background between the two disorders.

Objective: This study aimed to elucidate the distinct response patterns exhibited by patients diagnosed with bipolar disorder (BD) and those with major depressive disorder (MDD) through the application of the short version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A-SV). Methods: A total of 2,458 participants consisting of patients with MDD (n=288), BD (BD I, n=111; BD II, n=427), and control group (n=1,632) completed the TEMPS-A-SV. The response patterns of the participants were classified into distinct profiles using latent profile analysis. The study further examined the impact of covariates such as age, sex, and diagnostic group on derived latent profile memberships. Results: The following three latent profiles were identified: High Affective Temperament Group (17.86%), Low Affective Temperament Group (41.25%), and Middle Affective Temperament Group (40.89%). Compared with the patient group with MDD and BD, the control group was more likely to belong in the Low Affective Temperament Group, which showed a higher score on hyperthymic temperament than the Middle Affective Temperament Group. Furthermore, compared with the patients with BD, the MDD patients were more likely to be in the Low Affective Temperament Group rather than the Middle Affective Temperament Group. Conclusion These results indicate that different affective temperaments exist between patients with MDD and BD. Attempting to classify response patterns using the TEMPS-A-SV can help diagnose MDD and BD correctly.

Objective: Interpersonal sensitivity, characterized by a heightened awareness of others’ behavior and emotions, is linked to mood disorders. However, current literature lacks a comprehensive analysis of how some items of the Interpersonal Sensitivity Measure (IPSM) interrelate and contribute to the overall construct. This study constructed a network for interpersonal sensitivity symptomatology to identify core IPSM items in patients with mood disorders. Methods: The IPSM, a 36-item self-report scale, was utilized to evaluate interpersonal sensitivity symptoms in 837 participants (major depressive disorder [MDD], n=265; bipolar I disorder [BD I], n=126; and bipolar II disorder [BD II], n=446). We performed exploratory graph analysis, employing regularized partial correlation models to estimate the network structure. Centrality analysis identified core IPSM symptoms for each mood disorder group. Network comparison tests assessed structural differences between the MDD and BD subgroups. Results: Network analysis detected five communities. Item 10 (“I worry about being criticized for things that I have said or done”) showed the highest value in strength. Multiple items on “Interpersonal Worry/Dependency” and “Low Self-Esteem” showed high strength centrality. Network structure invariance and global strength invariance test results indicated no significant differences between the MDD and BD subgroups. Conclusion Our findings emphasize the importance of addressing “Interpersonal Worry/Dependency” and “Low Self-Esteem” in the IPSM network among mood disorder patients based on core items of the network. Additionally, targeted treatments and comprehensive strategies in this aspect could be crucial for managing mood disorders.