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.

: Depression is a frequent non-motor symptom of Parkinson’s disease (PD), and may even precede the onset of motor symptoms of parkinsonism. Beyond its negative influence on mood, depression in PD is frequently associated with other neuropsychiatric symptoms and with late-stage complications such as dementia. Despite its profound impact on the quality of life and cognitive functioning in PD, depression in PD is often under-recognized and poorly treated. : Pathophysiological studies demonstrated that depression in PD is associated with global dysfunction of interactions between discrete brain areas rather than focal structural or functional abnormalities, and that it is sustained by pathological changes of several neurotransmitter/receptor complexes. : In general, all traditional antidepressants and some dopamine agonists have been found to be safe and well-tolerated to treat depressive symptoms in PD, despite initial warning on worsening of parkinsonism. Available data suggest that the time-course of response differs among antidepressants. Efficacy results from clinical trials with antidepressant in PD are, however, rather uncertain, although pooled analysis suggests a moderate benefit. Several issues may critically impact the results of clinical trials with antidepressants in PD, including the correct psychiatric diagnosis, the overlap of symptoms between depression and PD, and the selection of appropriate end-points and rating scales.

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BACKGROUND Postoperative cognitive decline (pCD) occurs frequently (6 to 30%) after carotid endarterectomy (CEA), although there are no exact estimates and risk factors are still unclear. OBJECTIVE The objective of this study was to determine pCD incidence and risk factors in CEA patients. DESIGN We performed a systematic review and meta-analysis of both randomised and nonrandomised trials following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES We searched Cochrane, PubMed/Medline and Embase databases from the date of database inception to 1 December 2018. ELIGIBILITY CRITERIA We selected longitudinal studies including CEA patients with both pre-operative and postoperative cognitive assessments. Primary outcome was pCD incidence, differentiating delayed neurocognitive recovery (dNCR) and postoperative neurocognitive disorder (pNCD). dNCR and pNCD incidences were expressed as proportions of cases on total CEA sample and pooled as weighted estimates from proportions. Postoperative delirium was excluded from the study design. Secondary outcomes were patient-related (i.e. age, sex, diabetes, hypertension, contralateral stenosis, pre-operative symptoms, dyslipidaemia and statin use) and procedure-related (i.e. hyperperfusion, cross-clamping duration and shunting placement) risk factors for pCD. We estimated odds ratios (ORs) and mean differences through a random effects model by using STATA 13.1 and RevMan 5.3. RESULTS Our search identified 5311 publications and 60 studies met inclusion criteria reporting a total of 4823 CEA patients. dNCR and pNCD incidence were 20.5% [95% confidence interval (CI), 17.1 to 24.0] and 14.1% (95% CI, 9.5 to 18.6), respectively. pCD risk was higher in patients experiencing hyperperfusion during surgery (OR, 35.68; 95% CI, 16.64 to 76.51; P < 0.00001; I 2 = 0%), whereas dNCR risk was lower in patients taking statins before surgery (OR, 0.56; 95% CI, 0.41 to 0.77; P = 0.0004; I 2 = 19%). Sensitivity analysis revealed that longer cross-clamping duration was a predictor for dNCR (mean difference, 5.25 min; 95% CI, 0.87 to 9.63; P = 0.02; I 2 = 49%). CONCLUSION We found high incidences of dNCR (20.5%) and pNCD (14.1%) after CEA. Hyperperfusion seems to be a risk factor for pCD, whereas the use of statins is associated with a lower risk of dNCR. An increased cross-clamping duration could be a risk factor for dNCR. TRIAL REGISTRATION This systematic review was registered in the International Prospective Register of Systematic Reviews (CDR42017073633).