RNA-seq analysis of gene expression profiles in posttraumatic stress disorder, Parkinson's disease and schizophrenia identifies roles for common and distinct biological pathways.

Evidence suggests that shared pathophysiological mechanisms in neuropsychiatric disorders (NPDs) may contribute to risk and resilience. We used single-gene and network-level transcriptomic approaches to investigate shared and disorder-specific processes underlying posttraumatic stress disorder (PTSD), Parkinson's disease (PD) and schizophrenia in a South African sample. RNA-seq was performed on blood obtained from cases and controls from each cohort. Gene expression and weighted gene correlation network analyses (WGCNA) were performed using DESeq2 and CEMiTool, respectively. Significant differences in gene expression were limited to the PTSD cohort. However, WGCNA implicated, amongst others, ribosomal expression, inflammation and ubiquitination as key players in the NPDs under investigation. Differential expression in ribosomal-related pathways was observed in the PTSD and PD cohorts, and focal adhesion and extracellular matrix pathways were implicated in PD and schizophrenia. We propose that, despite different phenotypic presentations, core transdiagnostic mechanisms may play important roles in the molecular aetiology of NPDs.

DNA methylation and antipsychotic treatment mechanisms in schizophrenia: Progress and future directions.

Antipsychotic response in schizophrenia is a complex, multifactorial trait influenced by pharmacogenetic factors. With genetic studies thus far providing little biological insight or clinical utility, the field of pharmacoepigenomics has emerged to tackle the so-called "missing heritability" of drug response in disease. Research on psychiatric disorders has only recently started to assess the link between epigenetic alterations and treatment outcomes. DNA methylation, the best characterised epigenetic mechanism to date, is discussed here in the context of schizophrenia and antipsychotic treatment outcomes. The majority of published studies have assessed the influence of antipsychotics on methylation levels in specific neurotransmitter-associated candidate genes or at the genome-wide level. While these studies illustrate the epigenetic modifications associated with antipsychotics, very few have assessed clinical outcomes and the potential of differential DNA methylation profiles as predictors of antipsychotic response. Results from other psychiatric disorder studies, such as depression and bipolar disorder, provide insight into what may be achieved by schizophrenia pharmacoepigenomics. Other aspects that should be addressed in future research include methodological challenges, such as tissue specificity, and the influence of genetic variation on differential methylation patterns.

Fine-mapping of antipsychotic response genome-wide association studies reveals novel regulatory mechanisms.

AIM: Noncoding variation has demonstrated regulatory effects on disease treatment outcomes. This study investigated the potential functionality of previously implicated noncoding variants on schizophrenia treatment response. MATERIALS & METHODS: Predicted regulatory potential of variation identified from antipsychotic response genome-wide association studies was determined. Prioritized variants were assessed for association(s) with treatment outcomes in a South African first episode schizophrenia cohort (n = 103). RESULTS: Bioinformatic and association results implicated a relationship between regulatory variants, expression of MANBA, COL9A2 and NFKB1, and treatment response. Three SNPs were associated with poor outcomes (rs230493: p = 1.88 × 10-6; rs3774959: p = 1.75 × 10-5; and rs230504: p = 1.48 × 10-4). CONCLUSION: This study has thoroughly investigated previous GWAS to pinpoint variants that may play a causal role in poor schizophrenia treatment outcomes, and provides potential candidate genes for further study in the field of antipsychotic response.

Rapporteur summaries of plenary, symposia, and oral sessions from the XXIIIrd World Congress of Psychiatric Genetics Meeting in Toronto, Canada, 16-20 October 2015.

The XXIIIrd World Congress of Psychiatric Genetics meeting, sponsored by the International Society of Psychiatric Genetics, was held in Toronto, ON, Canada, on 16-20 October 2015. Approximately 700 participants attended to discuss the latest state-of-the-art findings in this rapidly advancing and evolving field. The following report was written by trainee travel awardees. Each was assigned one session as a rapporteur. This manuscript represents the highlights and topics that were covered in the plenary sessions, symposia, and oral sessions during the conference, and contains major notable and new findings.