Latent clinical-anatomical dimensions of schizophrenia

Abstract

AbstractWidespread structural brain abnormalities have been consistently reported in schizophrenia, but their relation to the heterogeneous clinical manifestations remains unknown. In particular, it is un-clear whether anatomical abnormalities in discrete regions give rise to discrete symptoms, or whether distributed abnormalities give rise to the broad clinical profile associated with schizophrenia. Here we apply a multivariate data-driven approach to investigate covariance patterns between multiple symptom domains and distributed brain abnormalities in schizophrenia. Structural MRI, and clinical data were derived from one discovery sample (133 patients, 113 controls) and one independent validation sample (108 patients, 69 controls). Disease-related voxel-wise brain abnormalities were estimated using deformation based morphometry. Partial least squares analysis was used to comprehensively map clinical, neuropsychological and demographic data onto distributed deformation in a single multivariate model. The analysis identified three latent clinical-anatomical dimensions that collectively accounted for 55% of the covariance between clinical data and brain deformation. The first latent clinical-anatomical dimension was replicated in an independent sample, encompassing cognitive impairments, negative symptom severity and brain abnormalities within the default mode and visual networks. This cognitive-negative dimension was associated with low socioeconomic status and was represented across multiple races. Altogether, we identified a continuous cognitive-negative dimension of schizophrenia, centered on two intrinsic networks. By simultaneously taking into account both clinical manifestations and neuroanatomical abnormalities, the present results open new avenues for multi-omic stratification and biotyping of individuals with schizophrenia.