Baseline brain structural and functional predictors of clinical outcome in the early course of schizophrenia

Abstract

Although schizophrenia is considered a brain disorder, the role of brain organization for symptomatic improvement remains inadequately defined. We investigated the relationship between baseline brain morphology, resting-state network connectivity and clinical response after 24-weeks of antipsychotic treatment in patients with schizophrenia (n = 95) using integrated multivariate analyses. There was no significant association between clinical response and measures of cortical thickness (r = 0.37, p = 0.98) and subcortical volume (r = 0.56, p = 0.15). By contrast, we identified a strong mode of covariation linking functional network connectivity to clinical response (r = 0.70; p = 0.04), and particularly to improvement in positive (weight = 0.62) and anxious/depressive symptoms (weight = 0.49). Higher internal cohesiveness of the default mode network was the single most important positive predictor. Key negative predictors involved the functional cohesiveness of central executive subnetworks anchored in the frontoparietal cortices and subcortical regions (including the thalamus and striatum) and the inter-network integration between the default mode and sensorimotor networks. The present findings establish links between clinical response and the functional organization of brain networks involved both in perception and in spontaneous and goal-directed cognition, thereby advancing our understanding of the pathophysiology of schizophrenia.

Figure 1:. Spatial Distribution of the Resting-State Networks and Subnetworks.

Details of the regions comprising each resting-state subnetwork are provided in Supplementary Table 3.

Figure 2:. Sparse Canonical Correlation Analysis of the Rs-fMRI and the Clinical Datasets.

(A) Single significant canonical mode linked the rs-fMRI measures and the clinical features (r=0.70, p=0.04). (B) Weights of each clinical variable in the sparse canonical correlation analysis; rs-fMRI=resting state functional magnetic resonance imaging

Figure 3:. Brain Functional Predictors of Symptomatic Response in Schizophrenia.

(A) Links depict the canonical weights of the association between the clinical variate and the connectivity of the subnetworks depicted; Red links represent positive predictors, Blue links represent negative predictors. Panels (B) and (C) provide illustrative examples of the associations between functional integration and improvement in positive symptoms. Improvement in positive symptoms was chosen because it had the highest canonical weight to the rs-fMRI variate. DMN1=medial temporal default mode subnetwork; DMN3=anterior precuneus/posterior cingulate cortex; DMN4= dorsal posterior precuneus; SMN2=sensorimotor network, dorsal subnetwork; rs-fMRI=resting state functional magnetic resonance imaging; details of the spatial distribution of the networks are provided in Figure 1 and Supplementary Table 3.