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Structural and functional deficits associated with schizophrenia are observed prior to the onset of psychosis and differ according to the stage of illness. However, most previous studies concentrated on a limited period during the illness, and it remains uncertain how these abnormalities develop throughout the entire disease course. In the current study, we investigated the gray matter (GM) and regional neural activity alterations in subjects at 4 different stages of schizophrenia. The subjects comprised 53 genetic high risk (HR) individuals, 26 ultra-high risk (UHR) individuals, 58 patients with first-episode schizophrenia (FES), 41 patients with chronic schizophrenia (ChSz) and 39 healthy controls (HC), all of whom underwent structural and resting-state functional MRI scanning. Gray matter volume (GMV), amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) values were compared voxelwise among the five groups using voxel-based morphometry (VBM) and the software REST. Correlations among structural, functional abnormalities and PANSS scores in the FES group were evaluated by partial correlation analysis and multiple stepwise regression. Pronounced GMV decline was observed in the bilateral occipital lobe, left orbital frontal cortex, bilateral superior parietal lobule (SPL), right middle temporal gyrus (MTG), gyrus rectus and medial superior frontal gyrus (SFG) in the FES group and in the bilateral occipital lobe in the HR group. The FES patients also showed increased ALFF in the caudate and decreased ReHo in the bilateral inferior parietal lobule (IPL) and precuneus. The ChSz patients displayed increased ALFF in the right hippocampus. The GMV of the right MTG and SPL and the ReHo of the precuneus were negatively correlated with the general psychopathology scale, while the GMV of the right MTG was negatively correlated with the total score on the Positive and Negative Syndrome Scale (PANSS). The GMV of the right occipital cortex and SPL were associated with the ALFF of the caudate, the GMV of the right SPL was associated with the ReHo of the bilateral IPL and precuneus. GM deficits and regional dysfunction are evident prior to the onset of psychotic symptoms and are more prominent during the onset of illness than during any other phase. The right MTG and SPL, the striatum and the DMN may play important roles in the pathological changes underlying schizophrenia. [ABSTRACT FROM AUTHOR]

Background The field of microbiota-gut-brain research in animals has progressed, while the exact nature of gut microbiota-brain-cognition relationship in humans is not completely elucidated, likely due to small sample sizes and single neuroimaging modality utilized to delineate limited aspects of the brain. We aimed to comprehensively investigate such association in a large sample using multimodal MRI. Methods Fecal samples were collected from 157 healthy young adults and 16S sequencing was used to assess gut microbial diversity and enterotypes. Five brain imaging measures, including regional homogeneity (ReHo) and functional connectivity density (FCD) from resting-state functional MRI, cerebral blood flow (CBF) from arterial spin labeling, gray matter volume (GMV) from structural MRI, and fractional anisotropy (FA) from diffusion tensor imaging, were jointly analyzed with a data-driven multivariate fusion method. Cognition was evaluated by 3-back and digit span tasks. Results We found significant associations of gut microbial diversity with ReHo, FCD, CBF, and GMV within the frontoparietal, default mode and visual networks, as well as with FA in a distributed set of juxtacortical white matter regions. In addition, there were FCD, CBF, GMV, and FA differences between Prevotella- versus Bacteroides-enterotypes in females and between Prevotella- versus Ruminococcaceae-enterotypes in males. Moreover, the identified neuroimaging fusion biomarkers could mediate the associations between microbial diversity and cognition. Conclusions Our findings not only expand existing knowledge of the microbiota-gut-brain axis, but also have potential clinical and translational implications by exposing the gut microbiota as a promising treatment and prevention target for cognitive impairment and related brain disorders. • Gut microbiota-brain-cognition association was assessed using multimodal MRI. • Multimodal MRI measures were jointly analyzed with a multivariate fusion method. • Gut microbial diversity was correlated with multiple neuroimaging fusion measures. • There were differences in multiple neuroimaging fusion measures between enterotypes. • Fusion biomarkers mediated the relations between microbial diversity and cognition. [ABSTRACT FROM AUTHOR]

Low vitamin D is linked to major depressive disorder (MDD) through affecting the brain. Gender difference is apparent in MDD and vitamin D level. We aimed to examine the association between gender, vitamin D, clinical presentations, and brain functional connectivity in a large cohort of MDD patients and comparison subjects. Resting-state functional MRI data from 122 patients and 119 controls were collected to perform a combined analysis of functional connectivity density (FCD) and seed-based functional connectivity (FC). Peripheral venous blood samples were obtained to measure serum concentration of vitamin D (SCVD). Clinical presentations (symptoms profiles and cognition) were also assessed. We found an interaction of group and gender on SCVD in which MDD patients demonstrated lower SCVD than controls in females rather than males. Concurrently, lower SCVD was associated with worse cognitive performance (prospective memory and sustained attention). Compared with controls, female MDD patients showed reduced FCD and FC of the left middle frontal gyrus, which were related to lower SCVD. Importantly, these FCD and FC changes mediated the relationship between lower SCVD and cognitive dysfunction. Our findings suggest that functional connectivity abnormalities may serve as neural substrates underlying the associations between low vitamin D and cognitive impairments in female MDD patients, providing unique insight into treatment and prevention of MDD and its related cognitive dysfunction from the perspective of regulating circulating vitamin D. • Depressive patients exhibited lower vitamin D than controls in females but not males. • There is a female-specific relation between lower vitamin D and poorer cognition. • Depression-related functional connectivity changes related with vitamin D in females. • Connectivity changes mediated relations between vitamin D and cognition in females. [ABSTRACT FROM AUTHOR]

Functional stability is a newly developed dynamic functional connectivity approach. The objective of this study was to adopt functional stability to investigate diagnosis-associated abnormalities (patients vs. controls) and status-related changes (acute vs. remitted status) in brain function in major depressive disorder (MDD). 132 MDD patients and 102 healthy controls underwent resting-state functional MRI as well as clinical and cognitive assessment at baseline, with 48 patients completing follow-up examinations at an average of 7 months. Results showed no group differences in baseline functional stability and no longitudinal functional stability changes from acute to remitted status in patients. However, we found that baseline functional stability in the dorsal and ventral anterior cingulate cortex, calcarine sulcus, and middle occipital gyrus could predict improvement in depressive symptoms from acute to remitted status in MDD patients, with longitudinal functional stability changes in these regions related to the degree of symptom improvement. In addition, lower baseline functional stability in the inferior temporal gyrus could predict a greater improvement in sustained attention, which was associated with a greater functional stability increase in this region. Our findings highlight functional stability as a potential prognostic biomarker to predict and track disease progression or stratify MDD patients for optimizing disease management and treatment strategies. • Baseline functional stability could predict clinical improvement in MDD patients. • Longitudinal functional stability changes related to clinical improvement degree. • Baseline functional stability could predict cognitive improvement in MDD patients. • Longitudinal functional stability changes related to cognitive improvement degree. [ABSTRACT FROM AUTHOR]