Resting-state functional connectivity correlates of brain structural aging in schizophrenia.

A large body of research has shown that schizophrenia patients demonstrate increased brain structural aging. Although this process may be coupled with aberrant changes in intrinsic functional architecture of the brain, they remain understudied. We hypothesized that there are brain regions whose whole-brain functional connectivity at rest is differently associated with brain structural aging in schizophrenia patients compared to healthy controls. Eighty-four male schizophrenia patients and eighty-six male healthy controls underwent structural MRI and resting-state fMRI. The brain-predicted age difference (b-PAD) was a measure of brain structural aging. Resting-state fMRI was applied to obtain global correlation (GCOR) maps comprising voxelwise values of the strength and sign of functional connectivity of a given voxel with the rest of the brain. Schizophrenia patients had higher b-PAD compared to controls (mean between-group difference + 2.9 years). Greater b-PAD in schizophrenia patients, compared to controls, was associated with lower whole-brain functional connectivity of a region in frontal orbital cortex, inferior frontal gyrus, Heschl's Gyrus, plana temporale and polare, insula, and opercular cortices of the right hemisphere (rFTI). According to post hoc seed-based correlation analysis, decrease of functional connectivity with the posterior cingulate gyrus, left superior temporal cortices, as well as right angular gyrus/superior lateral occipital cortex has mainly driven the results. Lower functional connectivity of the rFTI was related to worse verbal working memory and language production. Our findings demonstrate that well-established frontotemporal functional abnormalities in schizophrenia are related to increased brain structural aging.

Executive control of language in schizophrenia patients with history of auditory verbal hallucinations: A neuropsychological and resting-state fMRI study.

BACKGROUND: As demonstrated by a plethora of studies, compromised executive functions (EF) and language are implicated in mechanisms of auditory verbal hallucinations (AVH), but the contribution of their interaction to AVH remains unclear. We hypothesized that schizophrenia patients with history of AVH (AVHh+) vs. without history of AVH (AVHh-) have a specific deficit of executive control of language and alterations in functional connectivity (FC) between the brain regions involved in EF and language, and these neuropsychological and neurophysiological traits are associated with each other. METHODS: To explore the executive control of language and its contribution to AVH, we used an integrative approach involving analysis of neuropsychological and resting-state fMRI data of 34 AVHh+, 16 AVHh-, and 40 healthy controls. We identified the neuropsychological and FC measures that differentiated between AVHh+, AVHh-, and HC, and tested the associations between them. RESULTS: AVHh+ were characterized by decreased category and phonological verbal fluency, utterance length, productivity in the planning tasks, and poorer retelling. AVHh+ had decreased FC between the left inferior frontal gyrus and the anterior cingulate cortex. Productivity in category verbal fluency was associated with the FC between these regions. CONCLUSIONS: Poor executive control of word retrieval and deficient programming of sentence and narrative related to more general deficits of planning may be the neuropsychological traits specific for AVHh+. A neurophysiological trait specific for AVHh+ may be a decreased FC between regions involved in language production and differentiation between alien- vs. self-generated speech and between language production vs. comprehension.

Alterations in white matter microstructure and cortical thickness in individuals at ultra-high risk of psychosis: A multimodal tractography and surface-based morphometry study.

There is increasing evidence of white matter (WM) and grey matter pathology in subjects at ultra-high risk of psychosis (UHR), although a limited number of diffusion-weighted magnetic resonance imaging (DW-MRI) and surface-based morphometry (SBM) studies have revealed anatomically inconsistent results. The present multimodal study applies tractography and SBM to analyze WM microstructure, whole-brain cortical anatomy, and potential interconnections between WM and grey matter abnormalities in UHR subjects. Thirty young male UHR patients and 30 healthy controls underwent DW-MRI and T1-weighted MRI. Fractional anisotropy; mean, radial, and axial diffusivity in 18 WM tracts; and vertex-based cortical thickness, area, and volume were analyzed. We found increased radial diffusivity in the left anterior thalamic radiation and reduced bilateral thickness across the frontal, temporal, and parietal cortices. No correlations between WM and grey matter abnormalities were identified. These results provide further evidence that WM microstructure abnormalities and cortical anatomical changes occur in the UHR state. Disruption of structural connectivity in the prefrontal-subcortical circuitry, likely caused by myelin pathology, and cortical thickness reduction affecting the networks presumably involved in processing and coordination of external and internal information streams may underlie the widespread deficits in neurocognitive and social functioning that are consistently reported in UHR subjects.

Effects of a GWAS-Supported Schizophrenia Variant in the DRD2 Locus on Disease Risk, Anhedonia, and Prefrontal Cortical Thickness.

The study aimed to confirm the association of the schizophrenia genome-wide association study (GWAS) hit rs2514218 located near the DRD2 gene with the risk of the disease and to investigate the relationships between rs2514218 and schizophrenia-related clinical and neuroimaging phenotypes. Genotypes at the rs2514218 site were determined for 2148 schizophrenia spectrum patients and 1273 control subjects from the Russian population. In subsets of subjects, we assessed symptomatic dimensions using the Positive and Negative Syndrome Scale (n = 1651) and Temporal Experience of Pleasure Scale (n = 471). At the brain level, gray matter volumes in striatal structures and cortical thickness in the lateral prefrontal cortical regions were investigated (n = 97). Genotype frequencies did not differ between patients and controls. The allelic association analysis yielded a near-threshold p value (p = 0.054), the magnitude (OR = 0.90), and direction of the minor allele (T) effect being in accord with those in the schizophrenia GWAS. Also, patients homozygous for the risk allele C had more severe consummatory anhedonia and a thinner cortex than controls and patients carrying the T allele. The largest effect size of the genotype with diagnosis interaction was seen in the right pars opercularis area. The findings support the role of rs2514218 in schizophrenia risk and presentation and suggest rs2514218 has an influence on brain morphology and negative symptoms.