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Brain structural changes are known to be associated with psychotic symptoms, with worse symptoms consistently associated with brain volume loss in some areas. It is not clear whether volume and symptoms interfere with each other over the course of psychosis. In this paper, we analyse the temporal relationships between psychosis symptom severity and total gray matter volume. We applied a cross-lagged panel model to a public dataset from the NUSDAST cohorts. The subjects were assessed at three-time points: baseline, 24 months, and 48 months. Psychosis symptoms were measured by SANS and SAPS scores. The cohort contained 673 subjects with schizophrenia, healthy subjects and their siblings. There were significant effects of symptom severity on total gray matter volume and vice-versa. The worse the psychotic symptoms, the smaller the total gray volume, and the smaller the volume, the worse the symptomatology. There is a bidirectional temporal relationship between symptoms of psychosis and brain volume., Competing Interests: Declaration of competing interest Authors report no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Schizophrenia is a highly heterogeneous disorder, not only in its phenomenology but in its clinical course. This limits the usefulness of the diagnosis as a basis for both research and clinical management. Methods of reducing this heterogeneity may inform the diagnostic classification. With this in mind, we performed k-means clustering with symptom and cognitive measures to generate groups in a machine-driven way. We found that our data was best organised in three clusters: high cognitive performance, high positive symptomatology, low positive symptomatology. We hypothesized that these clusters represented biological categories, which we tested by comparing these groups in terms of brain volumetric information. We included all the groups in an ANCOVA analysis with post hoc tests, where brain volume areas were modelled as dependent variables, controlling for age and estimated intracranial volume. We found six brain volumes significantly differed between the clusters: left caudate, left cuneus, left lateral occipital, left inferior temporal, right lateral, and right pars opercularis. The k-means clustering provides a way of subtyping schizophrenia which appears to have a biological basis, though one that requires both replication and confirmation of its clinical significance., Competing Interests: Declaration of Competing Interest Authors report no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)