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Because major depressive disorder (MDD) and bipolar disorder (BD) manifest with similar symptoms, misdiagnosis is a persistent issue, necessitating their differentiation through objective methods. This study was aimed to differentiate between these disorders using a targeted proteomic approach. Multiple reaction monitoring-mass spectrometry (MRM-MS) analysis was performed to quantify protein targets regarding the two disorders in plasma samples of 270 individuals (90 MDD, 90 BD, and 90 healthy controls (HCs)). In the training set (72 MDD and 72 BD), a generalizable model comprising nine proteins was developed. The model was evaluated in the test set (18 MDD and 18 BD). The model demonstrated a good performance (area under the curve (AUC) >0.8) in discriminating MDD from BD in the training (AUC = 0.84) and test sets (AUC = 0.81) and in distinguishing MDD from BD without current hypomanic/manic/mixed symptoms (90 MDD and 75 BD) (AUC = 0.83). Subsequently, the model demonstrated excellent performance for drug-free MDD versus BD (11 MDD and 10 BD) (AUC = 0.96) and good performance for MDD versus HC (AUC = 0.87) and BD versus HC (AUC = 0.86). Furthermore, the nine proteins were associated with neuro, oxidative/nitrosative stress, and immunity/inflammation-related biological functions. This proof-of-concept study introduces a potential model for distinguishing between the two disorders.

Background In the new global socioeconomic development, suicidal deaths have increased which is progressively gaining more attention in the field of psychiatry, social work, psychology, and public health research. The present study aimed at examining the evidence for the attitudes towards suicide and risk factors for suicide attempts among university students in South Korea and suggested significant recommendations for future prevention programs and research. Method A study was conducted by reviewing recent publications and significant research journals published since 2000 related to the study objective, themes, and drawn broader perspectives and implications. The recent journal articles from PubMed, Global Health journal database, Google Scholar, MEDLINE, Academic Journals Database, WHO, and PsychInfo data sources were included. The study key terms were “suicide”, “attitudes”, “risk factors”, “university students”, & “South Korea”. Results The negative attitudes towards self, confusion of meaning in life, anxiety and stress about academic achievement, family problems, hopelessness, depression, and bipolar disorder were the main factors. Limitations We mainly included peer review journals in our study, but address the few relevant books and reports also. Conclusions The authors discussed important implications for future actions, including conducting relevant studies and regular collaborative discussions among responsible stakeholders.

Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551

Although early intervention may help prevent the progression of bipolar disorder, there are some controversies over early pharmacological intervention. In this study, we recruited 40 subjects in the prodromal stage of BD-II (BP), according to bipolar at-risk state criteria. We compared the expression of their plasma proteins with that of 48 BD-II and 75 healthy control (HC) to identify markers that could be detected in a high-risk state. The multiple reaction monitoring method was used to measure target peptide levels with high accuracy. A total of 26 significant peptides were identified through analysis of variance with multiple comparisons, of which 19 were differentially expressed in the BP group when compared to the BD-II and HC groups. Two proteins were overexpressed in the BP group; and were related to pro-inflammation and impaired neurotransmission. The other under-expressed peptides in the BP group were related to blood coagulation, immune reactions, lipid metabolism, and the synaptic plasticity. In this study, significant markers observed in the BP group have been reported in patients with psychiatric disorders. Overall, the results suggest that the pathophysiological changes included in BD-II had already occurred with BP, thus justifying early pharmacological treatment to prevent disease progression.

International audience; Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Background Early trauma is known to be a risk factor of suicide-related behavior. On the other hand, people who attempt suicide using a fatal method are reported to be more likely to complete suicide. In this study, we assumed that early trauma affects an individual's temperament and character and thereby increases the risk of a fatal method of suicide attempts. Methods We analyzed 92 people with a history of previous suicide attempts. We compared the Temperament and Character Inventory-Revised scores between the groups with and without early trauma, and between the groups with and without a history of suicide attempt using fatal methods through an analysis of covariance with age, sex, and presence of a psychiatric history as covariates. A mediation analysis was conducted of the relationship between early trauma and fatal methods of suicide attempt with self-transcendence as a mediator. Results Higher self-transcendence was reported in the fatal group (27.71 ± 13.78 vs. 20.97 ± 12.27, P = 0.010) and the early trauma group (28.05 ± 14.30 vs. 19.43 ± 10.73, P = 0.001), respectively. The mediation model showed that self-transcendence mediates the relationship between early trauma and fatal methods of suicide attempt. The 95% confidence intervals for the direct and indirect effect were (−0.559, 1.390) and (0.026, 0.947), respectively. Conclusion Self-transcendence may mediate the relationship between early trauma and fatal methods of suicide attempt. Self-transcendence may be associated with unhealthy defenses and suicidal behavior for self-punishment and may constitute a marker of higher suicide risk., Graphical Abstract

Depression is a common symptom of many mental disorders, especially major depressive disorder (MDD) and bipolar disorder (BD). Previous studies have reported that these diseases share common pathophysiological pathways; therefore, this study elucidated whether the plasma levels of protein markers related to common depressive symptoms differed between patients with BD and those with MDD. Plasma samples of 71 patients with mood disorders and clinical manifestations were analyzed in this study. After depleting the abundant proteins, liquid chromatography-tandem mass spectrometry and label-free quantification were performed. Five proteins, viz., cholesteryl ester transfer protein (CETP), apolipoprotein D (APOD), mannan-binding lectin serine protease 2 (MASP2), Ig lambda chain V-II region BO (IGLV2-8) and Ig kappa chain V-III region NG9 (IGKV3-20) were negatively associated with the total scores of the Hamilton depression rating scale (HAM-D), after adjusting for the covariates. CETP and APOD also showed significant negative correlations with the anhedonia/retardation and guilt/agitation scores of the HAM-D. Four proteins, namely, Ig kappa chain V-II region TEW (IGKC; IGKV2D-28), Ig lambda variable 5-45 (IGLV5-45), complement factor H (CFH) and attractin (ATRN), showed significant associations with anhedonia/retardation after adjusting for covariates. Proteins that significantly correlated with the symptoms could predict the remission state of depression (area under the curve [AUC], 0.83) and anhedonia/retardation (AUC, 0.80). Bioinformatics analysis revealed that complement activation, immune response, and lipid metabolism were significantly enriched pathways. Although our study design was cross-sectional and no controls were included, protein markers identified in this preliminary study will be further investigated in our subsequent longitudinal study.

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Background Major depressive disorder and bipolar disorder are prevalent and debilitating psychiatric disorders that are difficult to distinguish, as their diagnosis is based on behavioural observations and subjective symptoms. Quantitative protein profile analysis might help to objectively distinguish between these disorders and increase our understanding of their pathophysiology. Thus, this study was conducted to compare the peripheral protein profiles between the two disorders. Methods Serum samples were collected from 18 subjects with major depressive disorder and 15 subjects with bipolar disorder. After depleting abundant proteins, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and label-free quantification were performed. Data-dependent acquisition data were statistically analysed from the samples of 15 subjects with major depressive disorder and 10 subjects with bipolar disorder who were psychotropic drug-free. Two-sided t-tests were performed for pairwise comparisons of proteomes to detect differentially-expressed proteins (DEPs). Ingenuity Pathway Analysis of canonical pathways, disease and functions, and protein networks based on these DEPs was further conducted. Results Fourteen DEPs were significant between subjects with major depressive disorder and those with bipolar disorder. Ras-related protein Rab-7a (t = 5.975, p = 4.3 × 10− 6) and Rho-associated protein kinase 2 (t = 4.782, p = 8.0 × 10− 5) were significantly overexpressed in subjects with major depressive disorder and Exportin-7 (t = -4.520, p = 1.5 × 10− 4) was significantly overexpressed in subjects with bipolar disorder after considering multiple comparisons. Bioinformatics analysis showed that cellular functions and inflammation/immune pathways were significantly different. Conclusions Ras-related protein Rab-7a, Rho-associated protein kinase 2, and Exportin-7 were identified as potential peripheral protein candidates to distinguish major depressive disorder and bipolar disorder. Further large sample studies with longitudinal designs and validation processes are warranted.

BackgroundGiven its diverse disease courses and symptom presentations, multiple phenotype dimensions with different biological underpinnings are expected with bipolar disorders (BPs). In this study, we aimed to identify lifetime BP psychopathology dimensions. We also explored the differing associations with bipolar I (BP-I) and bipolar II (BP-II) disorders.MethodsWe included a total of 307 subjects with BPs in the analysis. For the factor analysis, we chose six variables related to clinical courses, 29 indicators covering lifetime symptoms of mood episodes, and 6 specific comorbid conditions. To determine the relationships among the identified phenotypic dimensions and their effects on differentiating BP subtypes, we applied structural equation modeling.ResultsWe selected a six-factor solution through scree plot, Velicer's minimum average partial test, and face validity evaluations; the six factors were cyclicity, depression, atypical vegetative symptoms, elation, psychotic/irritable mania, and comorbidity. In the path analysis, five factors excluding atypical vegetative symptoms were associated with one another. Cyclicity, depression, and comorbidity had positive associations, and they correlated negatively with psychotic/irritable mania; elation showed positive correlations with cyclicity and psychotic/irritable mania. Depression, cyclicity, and comorbidity were stronger in BP-II than in BP-I, and they contributed significantly to the distinction between the two disorders.ConclusionsWe identified six phenotype dimensions; in addition to symptom features of manic and depressive episodes, various comorbidities and high cyclicity constructed separate dimensions. Except for atypical vegetative symptoms, all factors showed a complex interdependency and played roles in discriminating BP-II from BP-I.

Liquid chromatography-mass spectrometry (LC-MS) method revealed the plasma metabolite profiles in major depressive disorder patients treated with escitalopram (ECTP) (n = 7). Depression severity was assessed according to the 17-item Hamilton Depression Rating Scale. Metabolic profiles were derived from major depressive disorder subject blood samples collected after ECTP treatment. Blood plasma was separated and processed in order to effectively extract metabolites, which were then analyzed using LC-MS. We identified 19 metabolites and elucidated their structures using LC-tandem MS (LC-MS/MS) combined with elemental compositions derived from accurate mass measurements. We further used online H/D exchange experiments to verify the structural elucidations of each metabolite. Identifying molecular metabolites may provide critical insights into the pharmacological and clinical effects of ECTP treatment and may also provide useful information informing the development of new antidepressant treatments. These detailed plasma metabolite analyses may also be used to identify optimal dose concentrations in psychopharmacotherapeutic treatment through drug monitoring, as well as forming the basis for response predictions in depressed subjects.

This is the first national survey study in South Korea investigating the relationship between suicide lethality and the clinical information of suicide attempters. An interview questionnaire was used to assess their sociodemographic factors, medical and psychiatric information, and two suicide scales, the Columbia-Suicide Severity Rating Scale and the Suicide Intent Scale. Suicide methods were categorized as low and high lethality; low lethality covered drug overdose or self-cutting behavior, and high lethality covered all other methods. High and low lethality suicide method groups were significantly different in demographic, medical, and psychiatric factors. The two scale score distributions differed significantly across two groups, and the difference was also valid for the subcategory analyses of the Suicide Intent Scale. Multiple factors such as older age, male sex, no previous psychiatric history, and previous suicide attempt, as well as high suicide intent by means of suicide scale, affect selection of suicide method of high lethality.

Objectives We provide an opportunity for implementing preventive interventions to decrease suicide mortality among prior suicide attempters. We aim to identify sex-specific high risk periods and factors for later suicide death among suicide attempters. Methods 8537 suicide attempters of Korea National Suicide Survey were collected from January 1, 2007 to December 31, 2011 and data on suicide death was obtained as of December 31, 2012. The risk period and risk factors for later suicide death was computed by Kaplan-Meier survival estimates and by plotting the hazard function using the Epanechnikov Kernal smoothing method and cox proportional hazard regression modeling. Results The hazard for later suicide death was significant up to 10 months for females and 20 months for males. Age 50–69 years (HR, 3.29; [CI: 1.80–6.02] and not being intoxicated with alcohol (HR, 1.94 [1.27–2.97])) in male attempters were significant risk factors for later suicide death. Conclusion Risk for later suicide death was significantly increased during the first full year following index attempts for all with an addition 8 months of risk for males, especially those of advanced age who were sober at the time of attempt.

Background Previous studies report that income inequality is an important risk factor for depression and suicide, and an increasing income gap appears inevitable. However, little study to date has investigated associations between the attribution of poverty and suicide. Though we previously reported associations between socio-cultural factors, including income, and suicide, we tried to explore more focused associations between income, attribution of poverty (individualistic, societal), permissive attitude toward suicide, and suicidal thought using a structural equation model. Methods A total of 2213 participants from each of three nations (South Korea, Japan, and the United States) completed an online survey. Participants without a history of psychological disorders or suicide attempts completed scales measuring attributions of poverty, attitudes toward suicide, and severity of suicidal thoughts. Results We established a structural equation model, which exhibited a good fit for all nations, and compared significant path coefficients by country. South Korea had the highest severity of suicidal thought and societal attribution of poverty, followed by Japan and America. In all nations, a permissive attitude was positively related to the severity of suicidal thought and individualistic attribution of poverty was positively related to a permissive attitude toward suicide. Societal attribution of poverty was positively associated with a permissive attitude in Japan and the United States. Income was negatively associated with the severity of suicide in South Korea and the United States. Conclusion Through an established structural equation model, we found the influence of poverty on suicide and identify the common and distinctive factors associated with suicide in each country.

Emerging high-throughput proteomic technologies have recently been considered as a powerful means of identifying substrates involved in mood disorders. We performed proteomic profiling using liquid chromatography-tandem mass spectrometry to identify dysregulated proteins in plasma samples of 42 and 45 patients with major depressive disorder (MDD) and bipolar disorder (BD), respectively, in comparison to 51 healthy controls (HCs). Fourteen and six proteins in MDD and BD patients, respectively, were differentially expressed compared to HCs, among which coagulation factor XIII A chain (F13A1), platelet basic protein (PPBP), platelet facor 4 (PF4), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and thymosin beta-4 (TMSB4X) were altered in both disorders. For proteins dysregulated in both, except F13A1, higher fold changes were observed in MDD than in BD patients. These findings may help identify candidate biomarkers of mood disorders and elucidate their underlying pathophysiology and biochemical abnormalities.

Objective Major depressive disorder (MDD) is a systemic and multifactorial disorder involving complex interactions between genetic predisposition and disturbances of various molecular pathways. Its underlying molecular pathophysiology remains unclear, and no valid and objective diagnostic tools for the condition are available. Methods We performed large-scale proteomic profiling to identify novel peripheral biomarkers implicated in the pathophysiology of MDD in 25 drug-free female MDD patients and 25 healthy controls. First, quantitative serum proteome profiles were obtained and analyzed by liquid chromatography–tandem mass spectrometry using serum samples from 10 MDD patients and 10 healthy controls. Next, candidate biomarker sets, including differentially expressed proteins from the profiling experiment and those identified in the literature, were verified using multiple-reaction monitoring in 25 patients and 25 healthy controls. The final panel of potential biomarkers was selected using multiparametric statistical analysis. Results We identified a serum biomarker panel consisting of six proteins: apolipoprotein D, apolipoprotein B, vitamin D-binding protein, ceruloplasmin, hornerin, and profilin 1, which could be used to distinguish MDD patients from controls with 68% diagnostic accuracy. Our results suggest that modulation of the immune and inflammatory systems and lipid metabolism are involved in the pathophysiology of MDD. Conclusions Our findings of functional proteomic changes in the peripheral blood of patients with MDD further clarify the molecular biological pathway underlying depression. Further studies using larger, independent cohorts are needed to verify the role of these candidate biomarkers for the diagnosis of MDD.

Governments and institutions across the world have made efforts to adopt and diffuse the health information exchange (HIE) technology with the expectation that the technology would improve the quality and efficiency of care by allowing providers online access to healthcare information generated by other providers at the point of care. However, evidence concerning the effectiveness of the technology is limited hindering the wide adoption of a HIE. The objective of this study was to assess impacts of a HIE on healthcare utilization and costs of patient episodes at a tertiary care hospital following referrals by clinic physicians.We studied 1265 HIE and 2702 non-HIE episodes after physicians referred patients from 35 HIE and 59 non-HIE clinics to Seoul National University Bundang Hospital (SNUBH) during a 17-month period from June 2009. We examined 9 measures of healthcare utilization and the magnitude of clinical information exchanged in 4 categories. We estimated the savings resulting from HIE use through linear regression models with dummy variables for HIE participation and patient classification codes controlling the case-mix differences between HIE and non-HIE cases.The total charges incurred by the HIE group during episodes at SNUBH were approximately 13% lower (P0.001), and the charges for clinical laboratory tests, pathological diagnosis, function tests, and diagnostic imaging were 54% (P0.001), 76% (P0.001), 73% (P0.001), and 80% (P0.001) lower for the HIE group than for the non-HIE group. SNUBH physicians had access to more clinical information for HIE than for non-HIE patients.HIE technology improved physicians' access to past clinical information, which appeared to reduce diagnostic test utilization and healthcare costs. The payer was the major beneficiary of HIE cost savings whereas providers paid for the technology. Fair allocation of benefits and costs among stakeholders is needed for wide HIE adoption.

Objectives: Many factors influence the likelihood of suicide attempts or deaths in persons with bipolar disorder. One key aim of the International Society for Bipolar Disorders Task Force on Suicide was to summarize the available literature on the presence and magnitude of effect of these factors. Methods: A systematic review of studies published from 1 January 1980 to 30 May 2014 identified using keywords ‘bipolar disorder’ and ‘suicide attempts or suicide’. This specific paper examined all reports on factors putatively associated with suicide attempts or suicide deaths in bipolar disorder samples. Factors were subcategorized into: (1) sociodemographics, (2) clinical characteristics of bipolar disorder, (3) comorbidities, and (4) other clinical variables. Results: We identified 141 studies that examined how 20 specific factors influenced the likelihood of suicide attempts or deaths. While the level of evidence and degree of confluence varied across factors, there was at least one study that found an effect for each of the following factors: sex, age, race, marital status, religious affiliation, age of illness onset, duration of illness, bipolar disorder subtype, polarity of first episode, polarity of current/recent episode, predominant polarity, mood episode characteristics, psychosis, psychiatric comorbidity, personality characteristics, sexual dysfunction, first-degree family history of suicide or mood disorders, past suicide attempts, early life trauma, and psychosocial precipitants. Conclusion: There is a wealth of data on factors that influence the likelihood of suicide attempts and suicide deaths in people with bipolar disorder. Given the heterogeneity of study samples and designs, further research is needed to replicate and determine the magnitude of effect of most of these factors. This approach can ultimately lead to enhanced risk stratification for patients with bipolar disorder.

Seasonality is one of the key features in subjects with mood disorders and is involved in the multi-faceted nature of the clinical course. However, few studies have explored the clinical implications of seasonality in bipolar disorders. We examined the differential effects of seasonality on clinical variables between bipolar I and II disorder (BD I and II). Seasonality was assessed using the Seasonal Pattern Assessment Questionnaire (SPAQ) in 204 subjects with BD I and 308 with BD II. Following the comparisons between BD I and II groups, clinical characteristics related to seasonality were explored. Next, to predict the presence of seasonality, a logistic regression model was applied. The global seasonality score on the SPAQ was significantly higher in the BD II group than in the BD I group. In the BD I group, seasonality was associated with suicide attempt history. In the BD II group, on the other hand, seasonality was associated with female gender, depressive predominance, and premenstrual dysphoric disorder (PMDD). In the regression models, the presence of PMDD and female gender was significantly associated with seasonality in the BD II group. Our findings suggest that high seasonality tendency, a vulnerability maker for cyclic worsening, may contribute to a differential pattern of clinical characteristics in BD II.

Lipidomic analysis can be used to efficiently identify hundreds of lipid molecular species in biological materials and has been recently established as an important tool for biomarker discovery in various neuropsychiatric disorders including major depressive disorder (MDD). In this study, quantitative targeted serum lipidomic profiling was performed on female subjects using liquid chromatography-mass spectrometry. Global lipid profiling of pooled serum samples from 10 patients currently with MDD (cMDD), 10 patients with remitted MDD (rMDD), and 10 healthy controls revealed 37 differentially regulated lipids (DRLs). DRLs were further verified using multiple-reaction monitoring (MRM) in each of the 25 samples from the three groups of independent cohorts. Using multivariate analysis and MRM data we identified serum biomarker panels of discriminatory lipids that differentiated between pairs of groups: lysophosphatidic acid (LPA)(16:1), triglycerides (TG)(44:0), and TG(54:8) distinguished cMDD from controls with 76% accuracy; lysophosphatidylcholines(16:1), TG(44:0), TG(46:0), and TG(50:1) distinguished between cMDD and rMDD at 65% accuracy; and LPA(16:1), TG(52:6), TG(54:8), and TG(58:10) distinguished between rMDD and controls with 60% accuracy. Our lipidomic analysis identified peripheral lipid signatures of MDD, which thereby provides providing important biomarker candidates for MDD.

Background Comorbidity of bipolar disorder (BD) and obsessive-compulsive disorder (OCD) has received clinical attention. However, the detailed nature and nolosogic validity of the comorbidity have not been fully explored. This study investigated the comorbidity rate, clinical nature, and correlates of OCD in patients with BD. Methods Patients (n = 314) with BD were recruited and lifetime clinical characteristics were evaluated comprehensively. The comorbid OCD (‘OCD-BD’) group and the ‘non-OC BD’ group were compared in terms of the clinical variables of BD. Results OCD was found in 15.9% of patients. Earlier age at onset, more frequent pharmacological (hypo)manic switch and a higher rate of comorbid panic disorder were associated with comorbid OCD. In two-thirds (65.4%) of the OCD-BD subjects, obsessive-compulsive symptoms worsened or were confined to depressive episodes. Contamination obsession and checking compulsion were the most common types of obsessive-compulsive symptoms. Drug-induced (hypo)manic switch was observed in more than 60% of the OCD-BD subjects who were previously exposed to antidepressants. None of the OCD-BD subjects were taking antidepressants for OCD in the current specialty clinics. Limitations Subject recruitment from specialty clinics, retrospective and cross-sectional evaluation, and difficulties in clarifying the causal relationships. Conclusions The comorbidity rate of OCD in Korean BD patients was comparable to that of Caucasian patients. Even though OCD seems to be more often linked to depressive episodes, a heterogeneous nosologic relationship including a possibility of drug-mediated induction is suggested.

Sleep-wake cycle disruption and seasonal variation in mood and behavior have been associated with mood disorders. This study aimed to investigate the lifetime characteristics of the sleep-wake cycle and its association with the lifetime characteristics of seasonality in individuals with bipolar disorder. Circadian preference, regularity of bed-rise time, and seasonality were evaluated on a lifetime basis using the Composite Scale of Morningness, the Sleep Timing Questionnaire, and the Seasonal Pattern Assessment Questionnaire in clinically stable individuals with bipolar I/II disorders (n = 103/97) and healthy controls (n = 270). Bipolar groups were more likely to have evening preference and irregular bed-rise time. These characteristics were interrelated and, particularly, more prevalent in bipolar II disorder. Seasonality, which was also more prevalent in the bipolar groups, was associated with evening preference and irregularity of the weekday bed-rise time.

OBJECTIVES: Bipolar disorder is associated with a high risk of suicide attempts and suicide death. The main objective of the present study was to identify and quantify the demographic and clinical correlates of attempted and completed suicide in people with bipolar disorder. METHODS: Within the framework of the International Society for Bipolar Disorders Task Force on Suicide, a systematic review of articles published since 1980, characterized by the key terms bipolar disorder and 'suicide attempts' or 'suicide', was conducted, and data extracted for analysis from all eligible articles. Demographic and clinical variables for which ≥ 3 studies with usable data were available were meta-analyzed using fixed or random-effects models for association with suicide attempts and suicide deaths. There was considerable heterogeneity in the methods employed by the included studies. RESULTS: Variables significantly associated with suicide attempts were: female gender, younger age at illness onset, depressive polarity of first illness episode, depressive polarity of current or most recent episode, comorbid anxiety disorder, any comorbid substance use disorder, alcohol use disorder, any illicit substance use, comorbid cluster B/borderline personality disorder, and first-degree family history of suicide. Suicide deaths were significantly associated with male gender and first-degree family history of suicide. CONCLUSIONS: This paper reports on the presence and magnitude of the correlates of suicide attempts and suicide deaths in bipolar disorder. These findings do not address causation, and the heterogeneity of data sources should limit the direct clinical ranking of correlates. Our results nonetheless support the notion of incorporating diagnosis-specific data in the development of models of understanding suicide in bipolar disorder. Language: en

Objective The evidence of the association between depression and metabolic syndrome is increasing, but the existence of sex differences in this association remains controversial. The aim of this study was to investigate the association between subjective depressive symptoms and metabolic syndrome and each of its components by sex in the Korean population. Methods The study sample comprised 15,073 men and 15,034 women who underwent routine health examinations. They completed the Beck Depression Inventory for depressive symptoms, and medical examinations provided data regarding metabolic syndrome. Adjustments for age, marriage, cigarette smoking, alcohol use, exercise, education, cancer, stroke, angina, and thyroid disease were performed. The association between depressive symptoms and metabolic syndrome and each of its components was analyzed by multiple logistic regression. Results In women, depressive symptoms were associated with metabolic syndrome (OR = 1.35, 95% CI = 1.11–1.64, p = 0.002) and the high-density lipoprotein cholesterol component (OR = 1.26, 95% CI = 1.09–1.46, p = 0.002) of metabolic syndrome. There was also an association between the severity of depressive symptoms and metabolic syndrome in women (OR = 1.046, 95% CI = 1.002–1.091, p = 0.039). In men, depressive symptoms were inversely associated with the hypertension component of metabolic syndrome (OR = 0.73, 95% CI = 0.58–0.91, p = 0.005). Conclusions Subjective depressive symptoms were associated with metabolic syndrome only in women. Further research should consider sex differences and dyslipidemia.

Appropriate stress-coping strategies are needed to improve the outcome in the treatment of bipolar disorders, as stressful life events may aggravate the course of the illness. The aim of this study was to compare stress-coping behaviors between bipolar patients and healthy controls. A total of 206 participants comprising 103 bipolar patients fulfilling the Diagnostic and Statistical Manual for Axis I disorder fourth edition (DSM-IV) diagnostic criteria for bipolar I and II disorders and controls matched by age and sex were included in this study. Stress-coping behaviors were assessed using a 53-item survey on a newly-designed behavioral checklist. The characteristics of stress-coping behaviors between the two groups were compared by using t -test and factor analysis. Social stress-coping behaviors such as ‘journey', ‘socializing with friends', and ‘talking something over' were significantly less frequent in bipolar patients than controls. On the other hand, pleasurable-seeking behaviors such as ‘smoking', ‘masturbation', and ‘stealing' were significantly more frequent in bipolar patients than controls. These results suggest that bipolar patients may have more maladaptive stress-coping strategies than normal controls. It is recommended to develop and apply psychosocial programs to reduce maladaptive stress-coping behaviors of bipolar patients.

Objectives: Disturbances of the sleep–wake cycle and seasonality have been reported in patients with bipolar disorder (BD). Considering that BD seems to be a spectrum condition in terms of clinical and biological characteristics, circadian and seasonal rhythm related to BD could be detected in non-clinical individuals with subthreshold bipolarity. The aim of this study was to screen past hypomanic symptoms in non-clinical samples and investigate their association with deviated sleep–wake cycle and seasonality. Methods: Lifetime history of hypomanic symptoms was assessed with the Hypomania Checklist-32 (HCL-32). Circadian preference, variability of sleep–wake time and seasonal changes in mood and behavior were evaluated on a lifetime-basis in non-clinical adult samples (n = 313), using the Composite Scale of Morningness (CSM), the Sleep Timing Questionnaire (STQ), and the Seasonal Pattern Assessment Questionnaire (SPAQ). Results: Two subdomains of hypomanic symptoms were identified through factor analysis of HCL-32, i.e., “active/elated” factor and “irritable/risk-taking” factor. The HCL-32 total score (p

Objective Although self-esteem is thought to be an important psychological factor in bipolar disorder, little is known about implicit and explicit self-esteem in manic patients. In this study, we investigated differences in implicit and explicit self-esteem among bipolar manic patients, bipolar euthymic patients, and healthy controls using the Implicit Association Test (IAT). Methods Participants included 19 manic patients, 27 euthymic patients, and 27 healthy controls. Participants completed a self-esteem scale to evaluate explicit self-esteem and performed the self-esteem IAT to evaluate implicit self-esteem. Results There were no differences among groups in explicit self-esteem. However, there were significant differences among groups in implicit self-esteem. Manic patients had higher IAT scores than euthymic patients and a trend toward higher IAT scores than healthy controls. Conclusions Our findings suggest that, on the latent level, a manic state is not simply the opposite of a depressed state. Furthermore, there may be a discontinuity of implicit self-esteem between manic and euthymic states. These unexpected results may be due to characteristics of the study participants or the methods used to assess implicit self-esteem. Nevertheless, they provide greater insights on the psychological status of manic patients.

A growing body of evidence suggests that the circadian molecular system is involved in the pathogenic and therapeutic mechanisms underlying bipolar disorders. Lithium, a representative mood stabilizer, has been reported to induce the Period2 (PER2) gene; however, the underlying molecular mechanisms require further study. We found that lithium upregulated PER2 expression at the transcriptional level in neuronally differentiated SH-SY5Y human neuroblastoma cells. Promoter reporter analyses using serial deletions of the PER2 promoter revealed that two early growth response 1 (Egr1)-binding sites (EBS) between positions −180 and −100 are required for maximal activation of the PER2 promoter by lithium. Ectopic expression of Egr1 enhanced lithium-induced PER2 promoter activity, while a point mutation in EBS abolished it. Electrophoretic mobility shift assays and chromatin immunoprecipitation indicated that Egr1 bound directly to the PER2 promoter. Stimulation of the extracellular-signal regulated kinase (ERK)1/2/Elk1 pathway by lithium was functionally linked to PER2 expression through Egr1 induction, and lithium-induced PER2 expression was strongly attenuated by depletion of Egr1 by siRNA. Lithium also upregulated the expression of Per2 and Egr1 in mouse frontal cortex. Induction of Per2 by lithium was attenuated in Egr1−/− mice. In conclusion, lithium stimulates PER2 transcription through the ERK/Elk1/Egr1 pathway in neuronal cells, indicating a connection between the ERK-Egr1 pathway and a circadian gene system in the mechanism of action of lithium.

Weak cardiorespiratory coupling (CRC) has been suggested in patients with obstructive sleep apnea (OSA), but the effects of continuous positive airway pressure (CPAP) on CRC remain unclear. We investigated the effects of CPAP treatment on CRC in patients with severe OSA to examine possible reversibility of altered CRC.High-resolution electrocardiograms (ECGs) and respiratory signals were simultaneously recorded for 13 never-treated OSA patients at baseline and after CPAP treatment. The analyses were performed on a 15-min daytime recording of ECG and respiration. Heart rate variability (HRV) indices were extracted from ECGs. After computing the sample entropy (SampEn) to quantify the regularity of both heart rate (SampEn(RR)) and respiration rhythm (SampEn(resp)), cross-sample entropy (cross-SampEn) was calculated to measure the interaction between the two signals. Cross-SampEn denotes asynchrony between heart rate and respiration, and thus negatively correlates with CRC.Lower SampEn(RR) and higher cross-SampEn as well as a shift toward sympathetic dominance were found in OSA patients compared with age- and gender-matched controls. CPAP treatment was associated with improved sympathovagal balance, increased SampEn(RR), and enhanced CRC, corresponding to a decrease in the cross-SampEn value from 0.71±0.08 to 0.49±0.06 (P.001). The effect sizes for the CPAP-induced changes in sympathovagal balance, SampEn(RR), and cross-SampEn were medium to large (0.54-0.90).The findings of our study indicate reduced CRC in untreated OSA patients and suggest that CPAP treatment may reverse this abnormality.

Decreased semantic memory has been suggested as an early sign in Alzheimer's disease (AD). This study aimed to investigate qualitative differences in semantic network between AD patients and healthy community-dwelling elderly controls. Category fluency test (animal) was administered to 416 AD patients and 339 controls. Mini-Mental State Examination was administered to evaluate global cognition. Patterns of semantic organization were compared between the two groups using hierarchical clustering (HC) and multidimensional scaling (MDS). In HC analysis, whereas a logically organized semantic structure was observed in the control group with an elaborate use of general knowledge, the semantic structure of the patient group was not interpretable. In MDS mapping, two dimensions of domesticity and size were identified in the control group. The MDS map of AD patients showed mixed features of perception and emotion. Knowledge-based semantic associations may be impaired in AD patients, which can add an extra dimension to cognitive impairments in AD patients regardless of quantitative facets of cognitive dysfunction.

Background The gender ratio (male/female) of suicide rates greatly differs by country and by age group. These differences are accompanied by differences in the use of violent methods of suicide. Methods The gender ratio of suicide rates and the methods used were calculated from the most recently available official electronic mortality data published by the four countries (two Eastern (Korea and Japan) and two Western (Australia and the United states) countries) and from the World Health Organization [WHO] mortality database. Suicide gender ratios based on 95% Confidence intervals (CIs) were used to compare the countries between age groups. Results The gender ratio of suicide rates was higher in the United States (3.9) and Australia (3.3), where gender differences in suicide methods were more prominent, than in Korea (1.8) and Japan (2.7). In the United States and Australia, the gender ratios greatly increased in the elderly (age 70 years and over), with a higher use of firearms by men. The gender ratio of suicide rates was lowest (1.0) in the young (age 20–29) in Korea, where hanging was a more common method in women than in men. Limitations The study does not consider the various other factors that may have influenced gender differences of suicide rate. Conclusions These findings suggest that differences in suicide methods play a role in determining the differences in the gender ratio of suicide rates between countries. Because suicide methods varied with gender, age, and country and may play a role in the suicide rates of each group, these parameters should be taken into account in the design of suicide prevention measures.

Objectives In this study, we aimed to determine the role of genetic variations within the zinc finger protein 804A (ZNF804A) gene, a candidate for a psychosis risk-conferring gene, in the development of schizophrenia (SZ) and bipolar disorder (BP) in the Korean population. Methods A total of 921 patients with SZ, bipolar I (BP-I) and II (BP-II) disorder, and 502 control subjects participated in the study. Twenty-one tag single nucleotide polymorphisms (SNPs) across the genomic region of ZNF804A and seven reference SNPs based on previous reports were genotyped. We applied logistic regression analyses under additive, dominant and recessive models. Results Fifteen of the 28 SNPs showed a nominally significant association with at least one diagnostic group. However, none of these associations remained significant after false discovery rate (FDR) correction. As the trend of association was observed mostly in SZ and BP-I with similar patterns, we performed a post hoc analysis for the combined SZ and BP-I group. Five SNPs (rs2369595, rs6755404, rs10931156, rs12476147 and rs1366842) showed a significant association with an FDR-corrected P of

Objective Major depressive disorder (MDD) is a systemic and multifactorial disorder that involves abnormalities in multiple biochemical pathways and the autonomic nervous system. This study applied a machine-learning method to classify MDD and control groups by incorporating data from serum proteomic analysis and heart rate variability (HRV) analysis for the identification of novel peripheral biomarkers. Methods The study subjects consisted of 25 drug-free female MDD patients and 25 age- and sex-matched healthy controls. First, quantitative serum proteome profiles were analyzed by liquid chromatography-tandem mass spectrometry using pooled serum samples from 10 patients and 10 controls. Next, candidate proteins were quantified with multiple reaction monitoring (MRM) in 50 subjects. We also analyzed 22 linear and nonlinear HRV parameters in 50 subjects. Finally, we identified a combined biomarker panel consisting of proteins and HRV indexes using a support vector machine with recursive feature elimination. Results A separation between MDD and control groups was achieved using five parameters (apolipoprotein B, group-specific component, ceruloplasmin, RMSSD, and SampEn) at 80.1% classification accuracy. A combination of HRV and proteomic data achieved better classification accuracy. Conclusions A high classification accuracy can be achieved by combining multimodal information from heart rate dynamics and serum proteomics in MDD. Our approach can be helpful for accurate clinical diagnosis of MDD. Further studies using larger, independent cohorts are needed to verify the role of these candidate biomarkers for MDD diagnosis.

SummaryAims Bipolar disorder is characterized by behavioral changes such as risk-taking and increasing goal-directed activities, which may result from altered reward processing. Patients with bipolar disorder show impaired reward learning in situations that require the integration of reinforced feedback over time. In this study, we examined the behavioral and electrophysiological characteristics of reward learning in manic and euthymic patients with bipolar disorder using a probabilistic reward task. Methods Twenty-four manic and 20 euthymic patients with bipolar I disorder and 24 healthy control subjects performed the probabilistic reward task. We assessed response bias (RB) as a preference for the stimulus paired with the more frequent reward and feedback-related negativity (FRN) to correct identification of the rich stimulus. Results Both manic and euthymic patients showed significantly lower RB scores in the early learning stage (block 1) in comparison with the late learning stage (block 2 or block 3) of the task, as well as significantly lower RB scores in the early stage compared to healthy subjects. Relatively more negative FRN amplitude is elicited by no presentation of an expected reward, compared to that elicited by presentation of expected feedback. The FRN became significantly more negative from the early (block 1) to the later stages (blocks 2 and 3) in both manic and euthymic patients, but not in healthy subjects. Changes in RB scores and FRN amplitudes between blocks 2 and 3 and block 1 correlated positively in healthy controls, but correlated negatively in manic and euthymic patients. The severity of manic symptoms correlated positively with reward learning scores and negatively with the FRN. Conclusions These findings suggest that patients with bipolar disorder during euthymic or manic states have behavioral and electrophysiological alterations in reward learning compared to healthy subjects. This dysfunctional reward processing may be related to the abnormal decision-making or altered goal-directed activities frequently seen in patients with bipolar disorder.

We compared the characteristics of patients with bipolar disorder with and without a history of suicide attempts to identify the risk factors of suicide in this disorder. Among 212 patients with bipolar disorder, 44 (21.2%) patients had histories of suicide attempts. Suicide attempters were younger and more likely to be diagnosed with bipolar II. The variables that differentiated those who did from those who did not attempt suicide included age at first contact, lifetime history of antidepressant use, major depressive episode, mixed episode, auditory hallucinations, rapid cycling, the number of previous mood episodes, age of first depressive episode, and age of first psychotic symptoms. Strong predictors of suicide attempts were younger age at onset, lifetime history of auditory hallucinations, and history of antidepressant use. Antecedent depressive episodes and psychotic symptoms predicted the first suicide attempt in patients with bipolar disorder. This study could help clinicians to understand the major risk factors of suicidal behavior in bipolar disorder.

Objective: We examined physicians' perceived needs, benefits, and concerns regarding health information exchange (HIE) technology prior to experiencing it and their actual usage of exchanged information in care processes during an HIE pilot program in South Korea. Materials and Methods: We conducted a survey through a structured questionnaire to collect data on physician perceptions about an HIE prior to implementation. We analyzed responses using descriptive statistics and one-way analyses of variance. We also conducted a post-implementation survey through a computerized tool designed to collect data on physician assessment of HIE item usefulness. We defined two indices to measure the volume of information flow and usefulness for individual HIE items and analyzed the indices with Fisher's exact test. Results: Physicians' overall perceptions about the need for an HIE and benefits of the technology were positive despite their concerns about information safety and security, system costs, and disputes between care providers in cases of malpractice. We found that physician practice settings significantly influenced the details of their perceptions. In the both pre- and post-implementation studies, the most needed and valued information were pathology and lab results, diagnostic imaging, medication, and working diagnosis. Physicians most agreed with the benefit potentials in the quality domain, least agreed with those in time and cost savings of healthcare delivery, and least worried about the decrease in revenues resulting from the technology. Conclusions: The overall physician acceptance of the HIE technology in South Korea is promising, but the adoption and diffusion strategy needs to be tailored to the type of physician practice. Concerted efforts may be needed to realize the much-anticipated potential of healthcare cost savings.

Evidence from previous studies suggests autonomic dysregulation in patients with major depressive disorder (MDD). Antidepressant treatment may also affect central autonomic function. We investigated whether the type of antidepressant might be associated with the pattern of cardiorespiratory coordination in non-depressed women with recurrent MDD. Resting electrocardiograms and respiratory signals were simultaneously recorded from 38 euthymic women with recurrent MDD who were treated with either escitalopram (n=19) or venlafaxine (n=19) monotherapy and from 38 healthy women. Linear measures of heart rate variability were extracted to assess cardiac autonomic control. Sample entropy (SampEn) was computed to assess the complexity of heart rate and respiratory signals, and cross-SampEn was calculated to measure the nonlinear interaction of both signals. Significant decreases in the cardiovagal tone and cardiorespiratory coupling of women with recurrent MDD receiving venlafaxine, and tendencies toward lower cardiovagal tone and cardiorespiratory coupling in women with recurrent MDD receiving escitalopram were observed when compared with healthy controls. Effect sizes for these differences were large between women receiving venlafaxine and healthy controls. We found a positive association between cardiorespiratory decoupling and venlafaxine dose. Norepinephrine-enhancement, within a therapeutic dose range, seems to be closely associated with decreased vagal tone and reduced nonlinear coupling between heart rate and respiration in euthymic women with recurrent MDD. However, the effects of serotonin enhancement on cardiovagal tone should be considered. Our results suggest that the pharmacodynamic properties of antidepressants may affect autonomic regulation of women with recurrent MDD even in euthymic state.

Various formal thought disorders are presented as symptoms by manic patients including pressure of speech, flight of ideas, and more complex speech with strong emotional components. N400 is the event-related potential, in which amplitude is suggested to be a general index of efforts to retrieve stored semantic context, which depends on the stored representation itself and the retrieval cue stimuli. The present study examines N400 components induced by a word-matching task in manic patients, and compare these responses to those induced by the task in schizophrenia and healthy controls.Twenty manic patients, twenty schizophrenic patients, and twenty healthy controls performed the word-matching task, in which they were presented with 120 (60 congruent and 60 incongruent) word pairs, they were instructed to discriminate whether each word pair was congruent or incongruent. During the task, we recorded the electroencephalogram.Reaction time analysis revealed a main effect for priming, in which reaction times were longer in response to incongruent words than to congruent words in all three participant groups (F=43.1, p0.001) with no group effects (F=2.3, p=0.11). N400 analysis showed the main effect for priming (F=30.2, p0.001), for group (F=5.0, p=0.01), and the interaction of priming×group (F=4.6, p=0.02). Post-hoc analysis of this interaction revealed larger N400 amplitudes to congruent words in manic patients (F=4.0, p=0.02) and smaller N400 to incongruent words in schizophrenic patients than in other groups (F=6.1, p=0.004). No correlations were found between N400 and symptom severity within patient groups.These findings suggest that priming effects of contextually related word pairs are decreased in patients with bipolar mania, whereas priming N400 responses of contextually unrelated word pairs are increased in schizophrenia. This may be the neurophysiological evidence of abnormal automatic semantic processing in patients with bipolar mania, and it also reflects a qualitative difference in thought and speech disorders between bipolar manic and schizophrenia.

Background Bipolar disorder is a recurrent and cyclical illness frequently accompanied by psychotic symptoms. Detecting prodromes and enhancing coping skills for prodromal symptoms in bipolar patients are very important for relapse prevention. Psychotic features in bipolar patients are related to poor prognosis. We aimed to investigate the differences in prodromal symptoms and coping styles in psychotic and nonpsychotic bipolar patients. Methods Eighty-three euthymic bipolar patients with or without a history of manic psychosis were interviewed about their demographic, diagnostic, and clinical information and completed a 40-item checklist for prodromal symptoms. After the interview, they completed the Coping Inventory for Prodromes of Mania. Results The differences between the psychotic patients and the nonpsychotic patients were found in the prodromal durations, and a few prodromal symptoms such as afraid of going crazy ( P = .03), energetic-very active ( P = .01), and hearing hallucination ( P = .02). The psychotic patients showed a higher score of denial or blame than the nonpsychotic ones (1.92 ± 0.73 in nonpsychosis, 2.32 ± 0.84 in psychosis; P = .03). Logistic regression revealed that the duration of prodromes ( P = .02) and hearing hallucination ( P = .01) were related to the presence of psychotic features. Conclusion Psychotic patients had a tendency to use denial or blame coping strategy and to experience attenuated psychotic symptoms a little more during the prodromal period. Timely psychosocial approaches for detecting signs and enhancing coping strategies would improve the outcomes.

Objective Alterations in neuroelectrical activities coincide with major depressive disorder (MDD). This study examines the pattern of cerebral activity and cardiac autonomic parameters of euthymic women with recurrent MDD. Methods Resting electroencephalograms and electrocardiograms were recorded from 20 women with MDD receiving escitalopram and 40 matched and healthy women. We computed frontal alpha asymmetry to evaluate the interhemispheric balance. Parameters of heart rate variability were extracted to assess cardiac autonomic control. Sample entropy was used to assess the complexity of neurocardiac dynamics. The relationship between cardiovagal activity and alpha electroencephalogram was examined with a coherence analysis. Results Multivariable analysis of variance revealed a differential pattern of psychophysiologic variables between MDD patients and controls (p = .03). MDD was associated with a tendency toward lower left frontal activity (-0.06 [standard deviation = 0.14] versus 0.04 [0.17] lnμV(2), p = .04). Discriminant analysis demonstrated more right frontal activation, a lower high-frequency heart rate power spectrum, and a higher ratio of the low- to high-frequency heart rate power spectrum in patients with MDD compared with controls. Residual depressive symptoms (r = -0.09 to 0.11, p = .63-.99) and escitalopram dosage (r = -0.09 to 0.28, p = .22-.84) were not correlated with autonomic measures. Coherence between normalized high-frequency component of the heart rate power spectrum and alpha power was not significant (F3, p = .27; F4, p = .16). Conclusions Euthymic women with recurrent MDD have a distinctive psychophysiologic profile. This profile may reflect altered frontal activation and a reduced cardiovagal tone in depression.

People with bipolar disorder have abnormal emotional processing. We investigated the automatic and controlled emotional processing via a priming paradigm with subliminal and supraliminal facial exposure. We compared 20 euthymic bipolar patients and 20 healthy subjects on their performance in subliminal and supraliminal tasks. Priming tasks consisted of three different primes according to facial emotions (happy, sad, and neutral) followed by a neutral face as a target stimulus. The prime stimuli were presented subliminally (17 msec) or supraliminally (1000 msec). In subliminal tasks, both patients and controls judged the neutral target face as significantly more unpleasant (negative judgment shift) when presented with negative emotion primes compared with positive primes. In supraliminal tasks, bipolar subjects showed significant negative judgment shift, whereas healthy subjects did not. There was a significant group × emotion interaction for the judgment rate in supraliminal tasks. Our finding of persistent affective priming even at conscious awareness may suggest that bipolar patients have impaired cognitive control on emotional processing rather than automatically spreading activation of emotion.

The conference was chaired by Mark A. Frye, MD, Department of Psychiatry, The Mayo Clinic, Rochester, Minnesota, United States. The faculty were Kyooseob Ha, MD, PhD, Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, and the Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, Seoul, Republic of Korea; Shigenobu Kanba, MD, PhD, Department of Neuropsychiatry, University of Kyushu, Fukuoka-shi, Fukuoka, Japan; Tadafumi Kato, MD, PhD, Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Hirosawa, Wako, Saitama, Japan; Susan L. McElroy, MD, Department of Psychiatry and Behavioral Sciences, University of Cincinnati, and the Lindner Center of HOPE, Cincinnati, Ohio, United States; Aysegul Ozerdem, MD, PhD, Department of Psychiatry and the Department of Neuroscience, Dokuz Eylul University, Narlidere, Izmir, Turkey; Gustavo Vazquez, MD, PhD, Department of Neuroscience, University of Palermo, Buenos Aires, Argentina; and Eduard Vieta, MD, PhD, Bipolar Disorder Program and the Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.

Semantic cognition is one of the key factors in psychosocial functioning. The aim of this study was to explore the differences in pattern of semantic memory organization between euthymic patients with bipolar I and II disorders using the category fluency task. Study participants included 23 euthymic subjects with bipolar I disorder, 23 matched euthymic subjects with bipolar II disorder and 23 matched control subjects. All participants were assessed for verbal learning, recall, learning strategies, and fluency. The combined methods of hierarchical clustering and multidimensional scaling were used to compare the pattern of semantic memory organization among the three groups. Quantitative measures of verbal learning, recall, learning strategies, and fluency did not differ between the three groups. A two-cluster structure of semantic memory organization was identified for the three groups. Semantic structure was more disorganized in the bipolar I disorder group compared to the bipolar II disorder. In addition, patients with bipolar II disorder used less elaborate strategies of semantic memory organization than those of controls. Compared to healthy controls, strategies for categorization in semantic memory appear to be less knowledge-based in patients with bipolar disorders. A differential pattern of semantic memory organization between bipolar I and II disorders indicates a higher risk of cognitive abnormalities in patients with bipolar I disorder compared to patients with bipolar II disorder. Exploring qualitative nature of neuropsychological domains may provide an explanatory insight into the characteristic behaviors of patients with bipolar disorders.

Background Although seasonal affective disorder and premenstrual syndrome (PMS) are frequently observed in mood disorders, little is known as to whether lifetime traits of seasonality and premenstrual distress are related to bipolar disorder independent of mood episodes. This study aimed at investigating these two cyclic traits with respect to bipolar I and II disorders as well as evaluating the association between them. Methods Subjects included 61 female patients with bipolar I or II disorders and 122 healthy women. Seasonality and premenstrual symptoms were measured retrospectively on a lifetime basis using the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Premenstrual Symptoms Screening Tool (PSST). Results Patients showed higher global seasonality scores on the SPAQ compared to the normal controls. Further, the patient-control difference was more prominent in cases of bipolar II disorder ( p p = 0.001). The prevalence of moderate to severe PMS as indicated on the PSST was also signifcantly higher in bipolar II disorder patients (51.6%) as compared to controls (19.7%). A significant association between seasonality and PMS was observed in both patient and control groups. Conclusions The results suggested that female patients with bipolar disorder experience seasonal and premenstrual changes in mood and behavior regardless of their mood episodes, and traits of seasonality and PMS are associated with each other. A common biological mechanism of these two cyclic conditions may be involved in the development of the cyclicity of bipolar disorder.

Recent acceptance that obsessive-compulsive disorder (OCD) represents a heterogeneous phenomenon has underscored the need for dimensional approaches to this disorder. However little is known about the relation between neuropsychological functions and symptom dimensions. The purpose of this study was to identify the cognitive deficits correlated with specific symptom dimensions. Thirteen categories in the Yale-Brown Obsessive Compulsive Scale symptom checklist from 144 patients with OCD were analyzed by principal component analysis. Correlations between identified symptom dimensions and neuropsychological functioning, measured by the Boston Qualitative Scoring System, were analyzed. Five factors or dimensions were identified: contamination/cleaning, hoarding, symmetry/ordering, obsessions/checking, and repeating/counting. Dysfunctions in nonverbal memory and organizational strategies were related to the symmetry/ordering dimension and the obsessions/checking dimension, respectively. The results of the present study support a transculturally stable symptom structure for OCD. They also suggest the possibility that nonverbal memory dysfunction and organizational impairment are mediated by distinct obsessive-compulsive dimensions.

This naturalistic study explored long-term effectiveness of adjunctive lamotrigine therapy for bipolar II depression. We analyzed prospective data from 109 lamotrigine-treated outpatients with bipolar II depression inadequately responsive to mood stabilizers. Lamotrigine was added to prior treatment in a naturalistic fashion. Changes in depression severity were prospectively monitored for up to 52 weeks using a prospective mood chart and the Clinical Global Impressions-Bipolar Version-Severity (CGI-BP-S). Time to lamotrigine discontinuation during 52-week period was calculated using the Kaplan-Meier estimate. A significant reduction in the CGI-BP-S depression score was observed between baseline and week 52 with a large effect size. The discontinuation rates were 44.0% and 50.5% for the total sample and 14.3% and 22.9% for responders at 24 weeks and 52 weeks, respectively. A higher number of prior hospitalizations for depression and a history of attempted suicide were associated with poor response to adjunctive lamotrigine treatment. Sustained benefits of an open-label lamotrigine add-on were indicated in patients with bipolar II depression. Adjunctive usage of lamotrigine was safe and generally well-tolerated. The potential benefit of adjunctive lamotrigine treatment was suggested in patients with bipolar II disorder suffering from depressive symptoms. Large-scale controlled studies are needed to confirm the effectiveness of adjunctive lamotrigine therapy for bipolar II depression.

Backgrounds: This study aimed to elucidate the validity and reliability of the Korean version of the Mood Disorder Questionnaire (K-MDQ), which is a screening instrument developed for bipolar disorders. Methods: This study translated the MDQ into Korean to produce the K-MDQ. The K-MDQ was applied to 126 outpatients with bipolar disorder clinically diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and 112 controls without a psychiatric history. The long-term test-retest reliability with a 10-month interval was investigated in 30 bipolar outpatients. Results: The internal consistency (Cronbach α) of the K-MDQ was .88. The correlations between each item and the total score ranged from 0.43 to 0.76 and were all statistically significant (P < .001). Factor analysis revealed 3 factors that explained 59.5% of the total variance. The mean total score was higher in patients (8.48) than in controls (4.51) (P < .001). A total K-MDQ score of at least 7 was chosen as the optimal cutoff, with the 2 parts of the questionnaire on symptoms clustering and functional problems being excluded, since this provided good sensitivity (0.75) and specificity (0.69). The Pearson correlation coefficient for the total test-retest score was 0.63 (P < .001), and the intraclass correlation coefficient was 0.77 (P < .001; 95% confidence interval, 0.52-0.89). Conclusions: These findings demonstrated the adequate validity and reliability of the K-MDQ, suggesting that this instrument is useful for screening bipolar disorders in Korea. However, we recommend that the original criteria be modified to improve the sensitivity.

Even though a large body of data suggests the presence of various types of cognitive deficits in the unaffected relatives of schizophrenia patients, more study is needed to clarify the comparative sensitivities of specific cognitive measures for relative-control differences. In this study, the authors compared the cognitive profiles of unaffected siblings of schizophrenia patients and those of patients and normal controls, and attempted to identify cognitive markers that might be associated with genetic liability to schizophrenia. Eighty-eight clinically stable schizophrenia patients, 44 healthy patient siblings, and 100 normal controls were evaluated using comprehensive neuropsychological tests. The domain structure of the MATRICS consensus cognitive battery was adopted, and both domain scores and individual test scores were used in the analysis. Performances of the sibling group were intermediate between those of patients and controls on most measures. A significant difference between the sibling and control groups was observed only in the Category Fluency Test. This cognitive deficit might be caused by familial predisposition to schizophrenia and could be a candidate of endophenotype for schizophrenia.

The purpose of this retrospective study was to investigate the prevalence of bipolar depression and differentiate the factors that could predict bipolar disorder among filicidal depressive mothers.Among the offenders who were sentenced to undergo treatment at the National Institute of Forensic Psychiatry, Gongju, Korea, for committing filicide or attempting filicide during 1987 to 2006, 45 women were selected whose final diagnoses at discharge were major depressive disorder or bipolar disorder based on DSM-III-R and DSM-IV criteria. Retrospective medical chart review was performed, mainly focusing on the prevalence rate of bipolar depression, including the rate of diagnostic change during admission. We also investigated the characteristic symptoms of depressive episodes that could predict bipolar disorder.At admission, in only 24.4% of the patients (N = 11) was bipolar disorder diagnosed. However, on the basis of diagnosis at discharge, a bipolar disorder prevalence rate of 73.3% (N = 33) was found. Of the patients with major depressive disorder at admission, 64.7% (N = 22) were subsequently reclassified as having bipolar disorder based on newly observed hypomanic or manic episodes during the admission period. The significant (p.05) depressive symptoms at the time of filicide that could predict bipolar depression were the presence of postpartum-onset depression (95% CI = 1.45 to 160.88), psychotic symptoms (95% CI = 1.94 to 215.81), and nonaltruistic motivation for filicide (95% CI = 1.68 to 133.36).Our results suggest that mental health professionals should consider the possibility of bipolarity when they examine filicidal depressive mothers with postpartum-onset depression, psychotic symptoms, and nonaltruistic motivation for filicide.