Whole exome sequencing in dense families suggests genetic pleiotropy amongst Mendelian and complex neuropsychiatric syndromes.

Whole Exome Sequencing (WES) studies provide important insights into the genetic architecture of serious mental illness (SMI). Genes that are central to the shared biology of SMIs may be identified by WES in families with multiple affected individuals with diverse SMI (F-SMI). We performed WES in 220 individuals from 75 F-SMI families and 60 unrelated controls. Within pedigree prioritization employed criteria of rarity, functional consequence, and sharing by ≥ 3 affected members. Across the sample, gene and gene-set-wide case-control association analysis was performed with Sequence Kernel Association Test (SKAT). In 14/16 families with ≥ 3 sequenced affected individuals, we identified a total of 78 rare predicted deleterious variants in 78 unique genes shared by ≥ 3 members with SMI. Twenty (25%) genes were implicated in monogenic CNS syndromes in OMIM (OMIM-CNS), a fraction that is a significant overrepresentation (Fisher's Exact test OR = 2.47, p = 0.001). In gene-set SKAT, statistically significant association was noted for OMIM-CNS gene-set (SKAT-p = 0.005) but not the synaptic gene-set (SKAT-p = 0.17). In this WES study in F-SMI, we identify private, rare, protein altering variants in genes previously implicated in Mendelian neuropsychiatric syndromes; suggesting pleiotropic influences in neurodevelopment between complex and Mendelian syndromes.

Homozygous PLA2G6 (PARK 14) gene mutation associated neuropsychiatric phenotypes from southern India.

PLA2G6 gene associated neurodegenerative disorders resulting from homozygous c. 2222G > A (p.Arg741Gln) mutation were detected in two cases having variable neuropsychiatric phenotypic and imaging findings. Exome analysis helped identification of rare alleles, reinforcing ethnographic antecedents to geographical clustering of rare mutations and, essential to understanding biology of neurodegenerative disorders.

Suicide Prevention Strategies for General Hospital and Psychiatric Inpatients: A Narrative Review.

BACKGROUND: In-patient (IP) suicides contribute a small but significant proportion of overall suicides. Despite this, suicide prevention strategies focusing on the general hospital IP population remain relatively underresearched. This paper is intended to provide an overview of various proposed suicide prevention approaches in the general hospital, including psychiatric IP, settings, and their evidence base. METHODOLOGY: Electronic searches of MEDLINE through PubMed, ScienceDirect, and Google Scholar databases were performed to identify potentially relevant articles from inception till January 2019. The generated abstracts were systematically screened for their eligibility to be included in the review. Included articles were grouped under five broad themes: environmental modification, staff education, pharmacotherapy, psychotherapy, and brain stimulation. Data extraction was done using a structured proforma. RESULTS: Environmental modifications and educating the health care professionals appear to be the most promising strategies to reduce suicide-related mortality among IPs. Among pharmacological methods, ketamine has shown initial promise in reducing suicidal ideations. Follow-up data are lacking for most of the described methods. Limited but positive evidence exists for cognitive therapies focusing on the immediate postadmission period and brain stimulation techniques, and it warrants further replication. CONCLUSION: There is a striking paucity of original research on IP suicide prevention. Given the ethical and methodological issues in carrying out studies with IP suicide as the primary outcome, there is a need to focus on intermediate suicide outcome measures, such as knowledge, attitude, and skills among staff handlers of suicidal patients.

Biological rhythm impairment in bipolar disorder: A state or trait marker?

CONTEXT: There is limited research on biological rhythms in bipolar disorder (BD) from the Indian setting despite its intricate relationship with metabolic syndrome (MS) and functioning. AIMS: The study aimed to assess "trait marker" status of biological rhythms as well as correlates of biological rhythm impairment in euthymic BD. SETTING AND DESIGN: Cross-sectional observational study over 6 months was carried out in hospital setting. MATERIALS AND METHODS: Biological Rhythms Interview of Assessment in Neuropsychiatry Questionnaire (BRIAN) and Functioning Assessment Short Test (FAST) were used to assess biological rhythms and functioning, respectively. MS was diagnosed as per modified National Cholesterol Education Program- Adult Treatment Panel III. Depressive symptoms were assessed by the Hamilton Depression Rating Scale (HDRS). Euthymia was defined as symptomatic remission for at least 8 weeks. Ethical approval was taken. RESULTS: Fifty cases of euthymic BD and fifty apparently healthy controls were recruited. Total as well as certain domain-specific BRIAN and FAST scores were significantly higher in cases compared to controls. A significant positive correlation was found between the total BRIAN score with HDRS as well as FAST score. No correlation was obtained between biological rhythms and metabolic parameters. CONCLUSIONS: Our results support the hypothesis that biological rhythm impairment is a trait marker in patients with BD. The study supports the need for management of subsyndromal depressive symptoms even in inter-episodic period.