Disrupted sensorimotor and social–cognitive networks underlie symptoms in childhood-onset schizophrenia

Abstract

Schizophrenia is increasingly recognized as a neurodevelopmental disorder with altered connectivity among brain networks. In the current study we examined large-scale network interactions in childhood-onset schizophrenia, a severe form of the disease with salient genetic and neurobiological abnormalities. Using a data-driven analysis of resting-state functional magnetic resonance imaging fluctuations, we characterized data from 19 patients with schizophrenia and 26 typically developing controls, group matched for age, sex, handedness, and magnitude of head motion during scanning. This approach identified 26 regions with decreased functional correlations in schizophrenia compared to controls. These regions were found to organize into two function-related networks, the first with regions associated with social and higher-level cognitive processing, and the second with regions involved in somatosensory and motor processing. Analyses of across- and within-network regional interactions revealed pronounced across-network decreases in functional connectivity in the schizophrenia group, as well as a set of across-network relationships with overall negative coupling indicating competitive or opponent network dynamics. Critically, across-network decreases in functional connectivity in schizophrenia predicted the severity of positive symptoms in the disorder, such as hallucinations and delusions. By contrast, decreases in functional connectivity within the social-cognitive network of regions predicted the severity of negative symptoms, such as impoverished speech and flattened affect. These results point toward the role that abnormal integration of sensorimotor and social-cognitive processing may play in the pathophysiology and symptomatology of schizophrenia.

Linking resting‐state networks and social cognition in schizophrenia and bipolar disorder

“…We also found reduced functional connectivity of the sensorimotor network in schizophrenia compared to healthy controls, similar to prior studies (e.g., Berman et al, 2016). Sensorimotor regions are implicated in low-level shared representations of action perception, or mirroring (e.g., Caspers, Zilles, Laird, & Eickhoff, 2010;Iacoboni, 2009).…”

“…Studies of the DMN in schizophrenia have shown both hypoconnectivity and hyperconnectivity within the network compared to controls (Fornito, Zalesky, Pantelis, & Bullmore, 2012;Narr & Leaver, 2015;Sheffield & Barch, 2016). DMN connectivity with sensorimotor and affective networks is also reduced (Berman et al, 2016;Martino et al, 2018).…”

Shared atypical default mode and salience network functional connectivity between autism and schizophrenia

“…In addition to the DMN and SN, intra‐SMN connectivity also plays an important role in discriminating schizophrenia from HCs. As reported in a recent study, intra‐SMN connectivity is related to the severity of the positive symptoms of schizophrenia [Berman et al, ].…”

Environmental Induction of Neurodevelopmental Disorders

“…A recent paper by Berman et al (2016) describes the phenomenon of childhoodonset schizophrenia, a 'pure' form of the disorder observed without the often confusing correlates of an extended disease course (Lancaster and Hall 2016 Lancaster and Hall (2016) find that the results of Berman et al are compatible with a pathodevelopmental model in which patients with childhood-onset schizophrenia experience excessive 'over-pruning' of short-distance functional connections.…”