The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

IntroductionBetween 30 -50% of patients with major depressive disorder (MDD) do not respond to their first antidepressant trial. Genetic variants contribute to the variance in antidepressant response rates. The clinical utility of pharmacogenetics-based decision-support tools (DSTs) is uncertain and has been the topic of much debate. ObjectivesTo conducted a systematic review and meta-analysis of prospective, randomized controlled trials (RCTs) that examined pharmacogenetic-guided decision support tools (DSTs) relevant to depressive symptom remission in major depressive disorder (MDD). MethodsRandom-effects meta-analysis was performed on RCTs that examined the effect of DSTs on remission rates in MDD. RCT quality was assessed using the Cochrane Collaboration Criteria. FindingsA total of 1737 eligible subjects from five RCTs were examined. Individuals receiving pharmacogenetic-guided DST therapy (n = 887) were 1.71 (95% CI = 1.17 -2.48, p = 0.005) times more likely to achieve symptom remission relative to individuals who received treatment as usual (n = 850). ConclusionsMeta-analysis results showed pharmacogenetic-guided prescribing has a positive effect on the likelihood of achieving symptom remission in MDD. Pharmacogenetic-guided prescribing of antidepressants is superior to prescribing as usual in relation to remission likelihood, specifically among those with inadequate response or intolerability to previous psychotropic medications. References1. Bousman C, Eyre HA, Dunlop B et al (2019) Pharmacogenetic tests and depressive symptom remission: A meta-analysis of randomized controlled trials. Pharmacogenomics Journal.