De novo mutations identified by whole-genome sequencing implicate chromatin modifications in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic anxiety disorder with a substantial genetic basis and a broadly undiscovered etiology. Recent studies of de novo mutation (DNM) exome-sequencing studies for OCD have reinforced the hypothesis that rare variation contributes to the risk. We performed, to our knowledge, the first whole-genome sequencing on 53 parent-offspring families with offspring affected with OCD to investigate all rare de novo variants and insertions/deletions. We observed higher mutation rates in promoter-anchored chromatin loops (empirical P = 0.0015) and regions with high frequencies of histone marks (empirical P = 0.0001). Mutations affecting coding regions were significantly enriched within coexpression modules of genes involved in chromatin modification during human brain development. Four genes­SETD5, KDM3B, ASXL3, and FBL­had strong aggregated evidence and functionally converged on transcription's epigenetic regulation, suggesting an important OCD risk mechanism. Our data characterized different genome-wide DNMs and highlighted the contribution of chromatin modification in the etiology of OCD.

Increased plasma leptin as a novel predictor for psychopathological depressive symptoms in chronic schizophrenia.

BACKGROUND: Depressive symptoms are often seen in schizophrenia. The overlap in presentation makes it difficult to distinguish depressive symptoms from the negative symptoms of schizophrenia. The adipokine leptin was found to be altered in both depression and schizophrenia. There are few studies focusing on the prediction of leptin in diagnosis and evaluation of depressive symptoms in schizophrenia. OBJECTIVEAIMS: To assess the plasma leptin level in patients with schizophrenia and its relationships with depressive symptoms. METHODS: Cross-sectional studies were applied to (1) compare the levels of plasma leptin between schizophrenia (n=74) and healthy controls (n=50); and (2) investigate the relationship between plasma leptin levels and depressive subscores. RESULTS: (1) Plasma leptin levels were significantly higher in patients with schizophrenia than in healthy controls. (2) Correlation analysis revealed a significant negative association between leptin levels and the depressed factor scores on the Positive and Negative Syndrome Scale (PANSS). (3) Stepwise multiple regression analyses identified leptin as an influencing factor for depressed factor score on PANSS. CONCLUSION: Leptin may serve as a predictor for the depressive symptoms of chronic schizophrenia.

Cross-sectional study of attitudes about suicide among psychiatrists in Shanghai.

BACKGROUND: Attitudes and knowledge about suicide may influence psychiatrists' management of suicidal patients but there has been little research about this issue in China. METHODS: We used the Scale of Public Attitudes about Suicide (SPAS)--a 47-item scale developed and validated in China--to assess knowledge about suicide and seven specific attitudes about suicide in a sample of 187 psychiatrists from six psychiatric hospitals in Shanghai. The results were compared to those of 548 urban community members (assessed in a previous study). RESULTS: Compared to urban community members, psychiatrists were more likely to believe that suicide can be prevented and that suicide is an important social problem but they had more stigmatizing beliefs about suicidal individuals and felt less empathy for them. The belief that suicide can be prevented was more common among female psychiatrists than male psychiatrists but male psychiatrists felt more empathy for suicidal individuals. Only 37% of the psychiatrists correctly agreed that talking about suicide-related issues with an individual would not precipitate suicidal behavior and only 41% correctly agreed that those who state that they intend to kill themselves may actually do so. CONCLUSIONS: Many psychiatrists in Shanghai harbor negative attitudes about suicidal individuals and are concerned that directly addressing the issue with patients will increase the risk of suicide. Demographic factors, educational status and work experience are associated with psychiatrists' attitudes about suicide and, thus, need to be considered when training psychiatrists about suicide prevention.