There has been little investigation of the effects of past substance abuse (SA) on working memory (WM) impairments in schizophrenia. This study examined the behavioral and neurobiological impact of past SA (6 months or longer abstinence period) on WM in schizophrenia. Thirty-seven schizophrenia patients (17 with past SA and 20 without) and 32 controls (12 with past SA and 20 without) completed two versions of a two-back WM task during fMRI scanning on separate days. Analyses focused on regions whose patterns of activation replicated across both n-back tasks. Schizophrenia patients were significantly less accurate than controls on both n-back tasks. No main effects or interactions with past SA on WM performance were observed. However, several fronto-parietal-thalamic regions showed an interaction between diagnostic group and past SA. These regions were significantly more active in controls with past SA compared to controls without past SA. Schizophrenia patients with or without past SA either showed no significant differences, or patients with past SA showed somewhat less activation compared to patients without past SA during WM. These results suggest robust effects of past SA on WM brain functioning in controls, but less impact of past SA in schizophrenia. This is consistent with previous literature indicating less impaired neurocognition in schizophrenia with SA.

Background Autism spectrum disorder (ASD) and schizophrenia are neurodevelopmental conditions that are characterized by significant social impairment. Emerging genomic and neurobiological evidence has increasingly pointed to shared pathophysiologic mechanisms in the two disorders. Overlap in social impairment may reflect similar underlying neural dysfunction in social-cognitive brain networks, yet few studies have directly compared brain function and communication between those with ASD and schizophrenia. Methods Outpatients with schizophrenia (n = 36), ASD (n = 33), and healthy volunteers (n = 37) completed a visual perspective-taking task during functional neuroimaging at 3T to assess similarities and differences in fronto-temporal brain function and connectivity during social-cognitive processing. Analyses employed general linear models to examine differences in amplitude of BOLD-signal response between disorder groups, and computed functional connectivity coefficients to investigate differences in the connectivity profiles of networks implicated in social cognition. Results Despite similar behavioral impairments, participants with ASD and schizophrenia evidenced distinct neural abnormalities during perspective-taking. Functional activation results indicated reduced temporo-parietal junction and medial prefrontal activity in ASD compared to schizophrenia (all Puncor < .002). Functional connectivity analyses further revealed significantly greater local orbitofrontal connectivity in ASD than schizophrenia (all PFDR < .028) during perspective-taking. Differences in brain activation and connectivity were unrelated to antipsychotic medication dose. Conclusions Autism and schizophrenia are characterized by similar social-cognitive impairments that may stem from different underlying abnormalities in the functional organization and communication of the social brain.

Individuals with schizophrenia are burdened with impairments in functional outcome, despite existing interventions. The lack of understanding of the neurobiological correlates supporting adaptive function in the disorder is a significant barrier to developing more effective treatments. This research conducted a systematic and meta-analytic review of all peer-reviewed studies examining brain-functional outcome relationships in schizophrenia. A total of 53 (37 structural and 16 functional) brain imaging studies examining the neural correlates of functional outcome across 1631 individuals with schizophrenia were identified from literature searches in relevant databases occurring between January, 1968 and December, 2016. Study characteristics and results representing brain-functional outcome relationships were systematically extracted, reviewed, and meta-analyzed. Results indicated that better functional outcome was associated with greater fronto-limbic and whole brain volumes, smaller ventricles, and greater activation, especially during social cognitive processing. Thematic observations revealed that the dorsolateral prefrontal cortex, anterior cingulate, posterior cingulate, parahippocampal gyrus, superior temporal sulcus, and cerebellum may have role in functioning. The neural basis of functional outcome and disability is infrequently studied in schizophrenia. While existing evidence is limited and heterogeneous, these findings suggest that the structural and functional integrity of fronto-limbic brain regions is consistently related to functional outcome in individuals with schizophrenia. Further research is needed to understand the mechanisms and directionality of these relationships, and the potential for identifying neural targets to support functional improvement.

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Schizophrenia is characterized by marked impairments in a broad and diverse array of social-cognitive domains. Fundamental deficits in the ability to visualize and shift to the perspectives of others and the neural networks that support this ability may contribute to many of these impairments. This study sought to investigate deficits in prefrontal brain function and connectivity in patients with schizophrenia during visual perspective-taking, and the degree to which such deficits contribute to higher-order impairments in social cognition. A total of 20 outpatients with schizophrenia and 20 age- and gender-matched healthy volunteers completed a basic, visual perspective-taking task during functional magnetic resonance imaging, along with a behavioral assessment of theory of mind after neuroimaging. Results revealed hypoactivity in the medial prefrontal (anterior cingulate) and orbitofrontal cortices during perspective-taking trials compared to control trials in schizophrenia patients relative to healthy controls. In addition, patients demonstrated significant deficits in negative connectivity between medial prefrontal and medial-temporal regions during perspective-taking, which fully mediated behavioral impairments observed in theory of mind. These findings suggest that disruptions are present in the most fundamental aspects of perspective-taking in schizophrenia, and that these disruptions impact higher-order social information processing.