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Background Evidence for age related brain white matter (WM) abnormalities in schizophrenia (SZ) has been observed using MRI, and interpreted by various studies as reflecting either developmental, maturational and/or degenerative pathology. Such conflicting findings, mostly due to lack of longitudinal data and statistical power, have hindered consensus on patterns and trajectories of brain dysfunction in SZ. 'Big Data' provides a new and powerful means to identify subtle abnormalities across the course of SZ. We have accumulated and processed, what we believe the biggest, to-date, sample of thoughtfully harmonized diffusion MRI (dMRI) cross sectional data, and performed the study aimed at comprehensively characterizing age-related WM changes (trajectories) through the course of SZ. Methods Our dMRI data comprises a total of 1092 participants, aged between 14 and 65. This includes 600 individuals with SZ at different illness stages (383 males, 217 females, age: 31.3+/- 12) and 492 healthy controls-HC (275 males, 217 females, age: 29.8+/-13), from 13 different sites. Preprocessing and dMRI data harmonization based on the rotation invariant spherical harmonics were used to remove the nonlinear scanner and sequence differences across sites. All harmonized data was registered to a common template. Fractional Anisotropy (FA) for Whole Brain (WB) and 14 individual WM regions of interest (ROIs) were computed using a probabilistic tractography atlas. We modeled FA changes over age by quadratic curves (the best fitted model: highest adjusted r^2) and fitted separately to SZ and HC. Peak age and upper and lower bounds of the model were estimated after 5000 bootstraps. FA% differences were modeled at each age between SZ and HC for WB and each ROI, while sex was treated as a confound. The effect sizes (Cohen's d) between SZ and HC were also computed at each age. Finally, WM pathologies (i.e. based on between-group differences) were clustered into three groups according to d occurring along trajectory using kmeans. Results In WB, FA was lower in SZ comparing to HC at each age, but the percentage differences as well as d varied significantly by age (range of %FA change = [1.5 7], d = [.5 1.8]). Also, WB peaks of FA differed between groups, observed at the age of 33 in HC, shifted to the age of 27 in SZ. Three groups emerged from examining the degree of WM pathology across the age trajectories in ROIs, characterized by: 1).3

Background An auditory verbal hallucination (AVH), is typically defined as a perceptual experience of hearing a voice in the absence of a corresponding external source. AVH are key symptoms of schizophrenia and are a highly prevalent major clinical characteristic that severely handicaps the patients. AVH can cause severe impairment in quality of life and a considerable proportion of patients do not respond to available treatment options. The voices that patients experience hearing are often with emotional content which may differ from individuals hearing voices in the general population. Translational approach suggests that AVH implicate speech perception areas in the left temporal lobe, thereby impairing the perception of and attention to external sounds. It is unknown weather amygdala is implicated in the emotional content of the voices or even may distinguish between AVH with emotional content and without emotional content. Preliminary data suggests that patients with AVH with high emotional content may not respond to transcranial magnet stimulation (TMS). Here, we therefore tested whether resting state perfusion may distinguish in schizophrenia patients with AVH with and without emotional content. To our knowledge, this is the first study to explore resting state perfusion in patients with schizophrenia depending on the content of AVH. Methods In total, we included 48 schizophrenia spectrum patients and 40 age and gender matched healthy controls. We assessed AVH with the comprehensive assessment of schizophrenia history and the hallucination change scale as well as imaging on a 3T MRI scanner. AVH were currently present in 33 patients and 18 patients had AVH with emotional content. Patients did not differ in antipsychotic medication or positive symptoms. We compared whole brain perfusion using arterial spin labeling (ASL) over all, and between the groups using one-way ANCOVAs (F-test and T-tests). We applied threshold-free cluster enhancement (TFCE) and a statistical threshold of p < 0.05 family wise error corrected for multiple testing (FWE-corr). Results We found a group effect (F-test) within the superior temporal gyrus and T-tests revealed that patients with AVH had increased perfusion most prominently within the left superior temporal gyrus compared to heathy controls and patients without AVH. Furthermore, T-tests indicated perfusion within the limbic system to be specific to AVH with emotional content. Conclusions The STG has been suggested to play a key role in AVH in patients with schizophrenia. Thus, our results are highly compatible with increased superior temporal perfusion as a marker of AVH. Furthermore, distinguishable associations of rCBF with AVH with and without emotional content point to distinct underlying pathophysiology. Whether this may inform on therapy responds to transcranial magnet stimulation has to be further tested. [ABSTRACT FROM AUTHOR]