The application of microarray technology in schizophrenia research was heralded as paradigm-shifting, as it allowed for high-throughput assessment of cell and tissue function. This technology was widely adopted, initially in studies of postmortem brain tissue, and later in studies of peripheral blood. The collective body of schizophrenia microarray literature contains apparent inconsistencies between studies, with failures to replicate top hits, in part due to small sample sizes, cohort-specific effects, differences in array types, and other confounders. In an attempt to summarize existing studies of schizophrenia cases and non-related comparison subjects, we performed two mega-analyses of a combined set of microarray data from postmortem prefrontal cortices (n = 315) and from ex-vivo blood tissues (n = 578). We adjusted regression models per gene to remove non-significant covariates, providing best-estimates of transcripts dysregulated in schizophrenia. We also examined dysregulation of functionally related gene sets and gene co-expression modules, and assessed enrichment of cell types and genetic risk factors. The identities of the most significantly dysregulated genes were largely distinct for each tissue, but the findings indicated common emergent biological functions (e.g. immunity) and regulatory factors (e.g., predicted targets of transcription factors and miRNA species across tissues). Our network-based analyses converged upon similar patterns of heightened innate immune gene expression in both brain and blood in schizophrenia. We also constructed generalizable machine-learning classifiers using the blood-based microarray data. Our study provides an informative atlas for future pathophysiologic and biomarker studies of schizophrenia.

Distinct gene expression profiles can be detected in peripheral blood mononuclear cells (PBMCs) in patients with schizophrenia; however, little is known about the effects of antipsychotic medication. This study compared gene expression profiles in PMBCs from treatment-naive patients with schizophrenia before and after antipsychotic drug treatment. PBMCs were obtained from 10 treatment-naive schizophrenia patients before and 6 wk after initiating antipsychotic drug treatment and compared to PMBCs collected from 11 healthy community volunteers. Genome-wide expression profiling was conducted using Illumina HumanHT-12 expression bead arrays and analysed using significance analysis of microarrays. This analysis identified 624 genes with altered expression (208 up-regulated, 416 down-regulated) prior to antipsychotic treatment (p < 0.05) including schizophrenia-associated genes AKT1, DISC1 and DGCR6. After 6-8 wk treatment of patients with risperidone or risperidone in combination with haloperidol, only 106 genes were altered, suggesting that the treatment corrected the expression of a large proportion of genes back to control levels. However, 67 genes continued to show the same directional change in expression after treatment. Ingenuity® pathway analysis and gene set enrichment analysis implicated dysregulation of biological functions and pathways related to inflammation and immunity in patients with schizophrenia. A number of the top canonical pathways dysregulated in treatment-naive patients signal through AKT1 that was up-regulated. After treatment, AKT1 returned to control levels and less dysregulation of these canonical pathways was observed. This study supports immune dysfunction and pathways involving AKT1 in the aetiopathophysiology of schizophrenia and their response to antipsychotic medication.

We found evidence of prevalent potential 'off-label' use for psychotropic medication, which may be due to PBs. We also found evidence of potential diagnostic-overshadowing, where symptoms of psychiatric co-morbidity may have been attributed to PBs. Our findings provide renewed importance, across borders and health systems, for clinicians to consider a holistic approach to treating PBs, and attempting to best understand the precipitants and predisposing factors before psychotropic prescribing.

BackgroundSri Lanka has one of the highest suicide rates in the world. Gatekeeper programs aimed at specific target groups could be a promising suicide prevention strategy in the country. The aim of this study was to develop guidelines that help members of the public to provide first aid to persons in Sri Lanka who are at risk of suicide.MethodsThe Delphi method was used to elicit consensus on potential helping statements to include in the guidelines. These statements describe information members of the public should have and actions they can take to help a person who is experiencing suicidal thoughts. An expert panel, comprised of mental health and suicide experts in Sri Lanka, rated each statement. The panellists were encouraged to suggest any additional action that was not included in the original questionnaire and, in particular, to include items that were culturally appropriate or gender specific. Responses to open-ended questions were used to generate new items. These items were included in the subsequent Delphi rounds. Three Delphi rounds were carried out. Statements were accepted for inclusion in the guidelines if they were endorsed (rated as essential or important) by at least 80 % of the panel. Statements endorsed by 70–79 % of the panel were re-rated in the following round. Statements with less than 70 % endorsement, or re-rated items that did not receive 80 % or higher endorsement were rejected.ResultsThe output from the Delphi process was a set of endorsed statements. In the first round questionnaire 473 statements were presented to the panel and 58 new items were generated from responses to the open-ended questions. Of the total 531 statements presented, 304 were endorsed. These statements were used to develop the suicide first aid guidelines for Sri Lanka.ConclusionBy engaging Sri Lankans who are experts in the field of mental health or suicide this research developed culturally appropriate guidelines for providing mental health first aid to a person at risk of suicide in Sri Lanka. The guidelines may serve as a basis for developing training for members of the public to provide mental health first aid to persons at risk of suicide as part of Sri Lanka’s suicide prevention strategy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13033-016-0085-3) contains supplementary material, which is available to authorized users.

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