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.

Self-suppression refers to the phenomenon that sensations initiated by our own movements are typically less salient, and elicit an attenuated neural response, compared to sensations resulting from changes in the external world. Evidence for self-suppression is provided by previous ERP studies in the auditory modality, which have found that healthy participants typically exhibit a reduced auditory N1 component when auditory stimuli are self-initiated as opposed to externally initiated. However, the literature investigating self-suppression in the visual modality is sparse, with mixed findings and experimental protocols. An EEG study was conducted to expand our understanding of self-suppression across different sensory modalities. Healthy participants experienced either an auditory (tone) or visual (pattern-reversal) stimulus following a willed button press (self-initiated), a random interval (externally initiated, unpredictable onset), or a visual countdown (externally initiated, predictable onset-to match the intrinsic predictability of self-initiated stimuli), while EEG was continuously recorded. Reduced N1 amplitudes for self- versus externally initiated tones indicated that self-suppression occurred in the auditory domain. In contrast, the visual N145 component was amplified for self- versus externally initiated pattern reversals. Externally initiated conditions did not differ as a function of their predictability. These findings highlight a difference in sensory processing of self-initiated stimuli across modalities, and may have implications for clinical disorders that are ostensibly associated with abnormal self-suppression.

Diffusion tensor imaging studies report childhood adversity (CA) is associated with reduced fractional anisotropy (FA) in multiple white matter tracts in adults. Reduced FA may result from changes in tissue, suggesting myelin/axonal damage, and/or from increased levels of extracellular free-water, suggesting atrophy or neuroinflammation. Free-water imaging can separately identify FA in tissue (FA) and the fractional volume of free-water (FW). We tested whether CA was associated with altered FA, FA, and FW in seven white matter regions of interest (ROI), in which FA changes had been previously linked to CA (corona radiata, corpus callosum, fornix, cingulum bundle: hippocampal projection, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, uncinate fasciculus). Tract-based spatial statistics were performed in 147 psychiatrically healthy adults who had completed a self-report questionnaire on CA primarily stemming from parental maltreatment. ROI were extracted according to the protocol provided by the ENIGMA-DTI working group. Analyses were performed both treating CA as a continuous and a categorical variable. CA was associated with reduced FA in all ROI (although categorical analyses failed to find an association in the fornix). In contrast, CA was only associated with reduced FA in the corona radiata, corpus callosum, and uncinate fasciculus (with the continuous measure of CA finding evidence of a negative relation between CA and FA in the fornix). There was no association between CA on FW in any ROI. These results provide preliminary evidence that childhood adversity is associated with changes to the microstructure of white matter itself in adulthood. However, these results should be treated with caution until they can be replicated by future studies which address the limitations of the present study.

Reduced integrity of the AFL is specifically associated with AVH, as opposed to schizophrenia in general or hallucinations in other modalities. Increased radial diffusivity suggests dysmyelination or demyelination of the AFL may play a role in AVH.