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.
Niacin has recently been demonstrated to lower blood pressure in hypertensive patients and to reduce cardiovascular events when combined with a statin. As a consequence, niacin has been elevated from being of historical interest as the treatment for pellagra, to being a compound with possible relevance to contemporary therapeutics. In spite of this, niacin deficiency leading to pellagra continues to be a health problem in some countries. Characterized by an exposed-site hyperpigmented dermatitis, pellagra is generally accepted to have been the first photosensitivity syndrome described. At its worst, pellagra manifests as one of the most striking examples of systemic photosensitivity. This is the only photosensitivity syndrome where death is included as a cardinal clinical feature (the often quoted four 'Ds': dermatitis, diarrhoea, dementia and death). However, the pathogenetic mechanism for the photosensitivity caused by niacin deficiency has yet to be determined. This review seeks to update the classification and phenotypic characterization of the various forms of niacin-deficient photosensitivity. Previous speculation about possible mechanisms for the pathogenesis of photosensitivity due to niacin deficiency is reviewed in the context of advances in the understanding of the photochemical basis of photosensitivity reactions. The review concludes by highlighting research required to advance the understanding of this photosensitivity syndrome.
The major environmental determinants of honeybee caste development come from larval nutrients: royal jelly stimulates the differentiation of larvae into queens, whereas beebread leads to worker bee fate. However, these determinants are not fully characterized. Here we report that plant RNAs, particularly miRNAs, which are more enriched in beebread than in royal jelly, delay development and decrease body and ovary size in honeybees, thereby preventing larval differentiation into queens and inducing development into worker bees. Mechanistic studies reveal that amTOR, a stimulatory gene in caste differentiation, is the direct target of miR162a. Interestingly, the same effect also exists in non-social Drosophila. When such plant RNAs and miRNAs are fed to Drosophila larvae, they cause extended developmental times and reductions in body weight and length, ovary size and fecundity. This study identifies an uncharacterized function of plant miRNAs that fine-tunes honeybee caste development, offering hints for understanding cross-kingdom interaction and co-evolution.
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