Overlapping but asymmetrical relationships between schizophrenia and autism revealed by brain connectivity

Abstract

<jats:title>(Abstract included 248 words)</jats:title><jats:p>Although the relationship between schizophrenia spectrum disorder (SSD) and autism spectrum disorder (ASD) has long been debated, it has not yet been fully elucidated. To address this issue, we took advantage of dual (ASD and SSD) classifiers that discriminate patients from their controls based on resting state brain functional connectivity. An SSD classifier using sophisticated machine-learning algorithms that automatically selected SSD- specific functional connections was applied to Japanese datasets including adult patients with SSD in a chronic stage. We demonstrated good performance of the SSD classification for independent validation cohorts. The generalizability was tested by USA and European cohorts in a chronic stage, and one USA cohort including first episode schizophrenia. The specificity was tested by two adult Japanese cohorts of ASD and major depressive disorder, and one European cohort of attention-deficit hyperactivity disorder. The weighted linear summation of the classifier’s functional connections constituted the biological dimensions representing neural liability to the disorders. Our previously developed robust ASD classifier constituted the ASD dimension. Distributions of individuals with SSD, ASD and healthy controls were examined on the SSD and ASD biological dimensions. The SSD and ASD populations exhibited overlapping but asymmetrical patterns on the two biological dimensions. That is, the SSD population showed increased liability on the ASD dimension, but not vice versa. Furthermore, the two dimensions were correlated within the ASD population but not the SSD population. Using the two biological dimensions based on resting-state functional connectivity enabled us to quantify and visualize the relationships between SSD and ASD.</jats:p>

Qualitative Differences in Attribution of Mental States to Other People in Autism and Schizophrenia: What are the Tools for Differential Diagnosis?

“…The relationship between ASD and SSD is consistent with a neurobiological model that suggests a common basis for ASD and SSD, with several genetic alterations or neuroimaging investigation (Biamino et al, 2016;de Lacy & King, 2013;King & Lord, 2010). Neuroimaging studies showed common abnormalities in gray matter volumes and brain activations (Cheung et al, 2010;Pinkham et al, 2008;Sugranyes et al, 2011;Yoshihara et al, 2020). Areas with the greatest overlap are those correlated with Social Cognition (SC).…”

Evidence of shared and distinct functional and structural brain signatures in schizophrenia and autism spectrum disorder

“…Our work provides evidence that SZ and ASD have a large common overlap (76–93%) in the functional changing patterns relative to HCs, primarily involving the DM, CC, and SM circuits. Although some studies have suggested that the two disorders are functionally related 24 , 40 , our work provides quantitative evaluation supporting they are largely overlapped in brain functional abnormality.…”

Dynamic functional network reconfiguration underlying the pathophysiology of schizophrenia and autism spectrum disorder

“…Both SZ and ASD have functional connectivity abnormalities as core disease features reported in previous studies. However, only a few works favor both diseases within a single study, showing most of the common and divergent connectivity alterations in default mode, salience, and motor networks (Chen, Uddin, et al, 2017; Mastrovito, Hanson, & Hanson, 2018; Yoshihara et al, 2020). These studies also have limitations, given that they are based on static connectivity which unfortunately represents a gross oversimplification (Allen et al, 2014).…”