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Deficits in social cognition (SC) interfere with recovery in schizophrenia (SZ) and may be related to resting state brain connectivity. This study aimed at assessing the alterations in the relationship between resting state functional connectivity and the social-cognitive abilities of patients with SZ compared to healthy subjects. We divided the brain into 246 regions of interest (ROI) following the Human Healthy Volunteers Brainnetome Atlas. For each participant, we calculated the resting-state functional connectivity (rsFC) in terms of degree centrality (DC), which evaluates the total strength of the most powerful coactivations of every ROI with all other ROIs during rest. The rs-DC of the ROIs was correlated with five measures of SC assessing emotion processing and mentalizing in 45 healthy volunteers (HVs) chosen as a normative sample. Then, controlling for symptoms severity, we verified whether these significant associations were altered, i.e., absent or of opposite sign, in 55 patients with SZ. We found five significant differences between SZ patients and HVs: in the patients' group, the correlations between emotion recognition tasks and rsFC of the right entorhinal cortex (R-EC), left superior parietal lobule (L-SPL), right caudal hippocampus (R-c-Hipp), and the right caudal (R-c) and left rostral (L-r) middle temporal gyri (MTG) were lost. An altered resting state functional connectivity of the L-SPL, R-EC, R-c-Hipp, and bilateral MTG in patients with SZ may be associated with impaired emotion recognition. If confirmed, these results may enhance the development of non-invasive brain stimulation interventions targeting those cerebral regions to reduce SC deficit in SZ., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Cognitive impairment has been associated with poor real-world functioning in patients with Schizophrenia. Previous studies have shown that pharmacological treatment with anticholinergic properties may contribute to cognitive impairment in Schizophrenia. We investigated the effect of the anticholinergic burden (ACB) on brain activity, cognition, and real-world functioning in Schizophrenia. We hypothesized that greater ACB would be associated with altered brain activity along with poorer cognitive performance and lower real-world functioning. A sample of 100 patients with a diagnosis of schizophrenia or schizoaffective disorder was recruited in the naturalistic multicenter study of the Italian Network for Research on Psychoses (NIRP) across 7 centres. For each participant, ACB was evaluated using the Anticholinergic Cognitive Burden scale. The association of ACB with brain function was assessed using BOLD fMRI during the N-Back Working Memory (WM) task in a nested cohort (N = 31). Real-world functioning was assessed using the Specific Level of Functioning (SLOF) scale. Patients with high ACB scores (≥3) showed lower brain activity in the WM frontoparietal network (TFCE corrected alpha <0.05) and poorer cognitive performance (p = 0.05) than patients with low ACB scores (<3). Both effects were unaffected by demographic characteristics, clinical severity, and antipsychotic dosage. Moreover, patients with high ACB showed poorer real-world functioning than patients with lower ACB (p = 0.03). Our results suggest that ACB in Schizophrenia is associated with impaired WM and abnormal underlying brain function along with reduced real-world functioning. Clinical practice should consider the potential adverse cognitive effects of ACB in the treatment decision-making process., Competing Interests: Declaration of competing interest Dr. Galderisi reported receiving personal fees from Angelini Pharma, Gedeon Richter-Recordati, Innova Pharma-Recordati Group, Janssen Pharmaceutica NV, Lundbeck Italia, Millennium Pharmaceutical, and Sunovion Pharmaceuticals outside the submitted work. Dr. Bertolino reported receiving grants and personal fees from Lundbeck and receiving personal fees from Janssen and from Otsuka during the conduct of the study. All other authors declare no biomedical financial interests and no potential conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Earlier evidence suggested that structural-functional covariation in schizophrenia patients (SCZ) is associated with cognition, a predictor of functioning. Moreover, studies suggested that functional brain abnormalities of schizophrenia may be related with structural network features. However, only few studies have investigated the relationship between structural-functional covariation and both diagnosis and functioning in SCZ. We hypothesized that structural-functional covariation networks associated with diagnosis are related to real-world functioning in SCZ., Methods: We performed joint Independent Component Analysis on T1 images and resting-state fMRI-based Degree Centrality (DC) maps from 89 SCZ and 285 controls. Structural-functional covariation networks in which we found a main effect of diagnosis underwent correlation analysis to investigate their relationship with functioning. Covariation networks showing a significant association with both diagnosis and functioning underwent univariate analysis to better characterize group-level differences at the spatial level., Results: A structural-functional covariation network characterized by frontal, temporal, parietal and thalamic structural estimates significantly covaried with temporo-parietal resting-state DC. Compared with controls, SCZ had reduced structural-functional covariation within this network (p FDR  = 0.005). The same measure correlated positively with both social and occupational functioning (both p FDR  = 0.042). Univariate analyses revealed grey matter deviations in SCZ compared with controls within this structural-functional network in hippocampus, cerebellum, thalamus, orbito-frontal cortex, and insula. No group differences were found in DC., Conclusions: Findings support the existence of a phenotypical association between group-level differences and inter-individual heterogeneity of functional deficits in SCZ. Given that only the joint structural/functional analysis revealed this association, structural-functional covariation may be a potentially relevant schizophrenia phenotype., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Previous evidence suggests reduced thalamic grey matter volume (GMV) in patients with schizophrenia (SCZ). However, it is not considered an intermediate phenotype for schizophrenia, possibly because previous studies did not assess the contribution of individual thalamic nuclei and employed univariate statistics. Here, we hypothesized that multivariate statistics would reveal an association of GMV in different thalamic nuclei with familial risk for schizophrenia. We also hypothesized that accounting for the heterogeneity of thalamic GMV in healthy controls would improve the detection of subjects at familial risk for the disorder. We acquired MRI scans for 96 clinically stable SCZ, 55 non-affected siblings of patients with schizophrenia (SIB), and 249 HC. The thalamus was parceled into seven regions of interest (ROIs). After a canonical univariate analysis, we used GMV estimates of thalamic ROIs, together with total thalamic GMV and premorbid intelligence, as features in Random Forests to classify HC, SIB, and SCZ. Then, we computed a Misclassification Index for each individual and tested the improvement in SIB detection after excluding a subsample of HC misclassified as patients. Random Forests discriminated SCZ from HC (accuracy=81%) and SIB from HC (accuracy=75%). Left anteromedial thalamic volumes were significantly associated with both multivariate classifications (p<0.05). Excluding HC misclassified as SCZ improved greatly HC vs. SIB classification (Cohen's d=1.39). These findings suggest that multivariate statistics identify a familial background associated with thalamic GMV reduction in SCZ. They also suggest the relevance of inter-individual variability of GMV patterns for the discrimination of individuals at familial risk for the disorder., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Anomalies in behavioral correlates of attentional processing and related brain activity are crucial correlates of schizophrenia and associated with familial risk for this brain disorder. However, it is not clear how brain functional connectivity during attentional processes is key for schizophrenia and linked with trait vs. state related variables. To address this issue, we investigated patterns of functional connections during attentional control in healthy siblings of patients with schizophrenia, who share with probands genetic features but not variables related to the state of the disorder. 356 controls, 55 patients with schizophrenia on stable treatment with antipsychotics and 40 healthy siblings of patients with this brain disorder underwent the Variable Attentional Control (VAC) task during fMRI. Independent Component Analysis (ICA) is allowed to identify independent components (IC) of BOLD signal recorded during task performance. Results indicated reduced connectivity strength in patients with schizophrenia as well as in their healthy siblings in left thalamus within an attentional control component and greater connectivity in right medial prefrontal cortex (PFC) within the so-called Default Mode Network (DMN) compared to healthy individuals. These results suggest a relationship between familial risk for schizophrenia and brain functional networks during attentional control, such that this biological phenotype may be considered a useful intermediate phenotype in order to link genes effects to aspects of the pathophysiology of this brain disorder., (Copyright © 2016 Elsevier B.V. All rights reserved.)