Research from JAMA Psychiatry — Progressive Gray Matter Reduction of the Superior Temporal Gyrus During Transition to Psychosis

Anomalous patterns of brain gyrification have been reported in major psychiatric disorders, presumably reflecting their neurodevelopmental pathology. However, previous reports presented conflicting results of patients having hyper-, hypo-, or normal gyrification patterns and lacking in transdiagnostic consideration. In this article, we systematically review previous magnetic resonance imaging studies of brain gyrification in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder at varying illness stages, highlighting the gyral pattern trajectory for each disorder. Patients with each psychiatric disorder may exhibit deviated primary gyri formation under neurodevelopmental genetic control in their fetal life and infancy, and then exhibit higher-order gyral changes due to mechanical stress from active brain changes (e.g., progressive reduction of gray matter volume and white matter integrity) thereafter, representing diversely altered pattern trajectories from those of healthy controls. Based on the patterns of local connectivity and changes in neurodevelopmental gene expression in major psychiatric disorders, we propose an overarching model that spans the diagnoses to explain how deviated gyral pattern trajectories map onto clinical manifestations (e.g., psychosis, mood dysregulation, and cognitive impairments), focusing on the common and distinct gyral pattern changes across the disorders in addition to their correlations with specific clinical features. This comprehensive understanding of the role of brain gyrification pattern on the pathophysiology may help to optimize the prediction and diagnosis of psychiatric disorders using objective biomarkers, as well as provide a novel nosology informed by neural circuits beyond the current descriptive diagnostics.

To date, a large number of magnetic resonance imaging (MRI) studies have been conducted in schizophrenia, which generally demonstrate gray matter reduction, predominantly in the frontal and temporo‐limbic regions, as well as gross brain abnormalities (e.g., a deviated sulcogyral pattern). Although the causes as well as timing and course of these findings remain elusive, these morphologic changes (especially gross brain abnormalities and medial temporal lobe atrophy) are likely present at illness onset, possibly reflecting early neurodevelopmental abnormalities. In addition, longitudinal MRI studies suggest that patients with schizophrenia and related psychoses also have progressive gray matter reduction during the transition period from prodrome to overt psychosis, as well as initial periods after psychosis onset, while such changes may become almost stable in the chronic stage. These active brain changes during the early phases seem to be relevant to the development of clinical symptoms in a region‐specific manner (e.g., superior temporal gyrus atrophy and positive psychotic symptoms), but may be at least partly ameliorated by antipsychotic medication. Recently, increasing evidence from MRI findings in individuals at risk for developing psychosis has suggested that those who subsequently develop psychosis have baseline brain changes, which could be at least partly predictive of later transition into psychosis. In this article, we selectively review previous MRI findings during the course of psychosis and also refer to the possible clinical applicability of these neuroimaging research findings, especially in the diagnosis of schizophrenia and early intervention for psychosis.