T164. STRUCTURAL COVARIANCE IN DRUG-NAïVE FIRST EPISODE PSYCHOSIS: AN ULTRA-HIGH FIELD MRI STUDY

Abstract

BackgroundStructural neuroimaging studies report disrupted morphological relationship in the grey matter volume (structural covariance) in patients with schizophrenia, indicating an impairment in functional and/or developmental plasticity. To our knowledge, no studies have examined the alterations in structural covariance across the entire brain in drug-naïve first episode psychosis. TOPSY (Tracking Outcomes of Psychosis) is one of the first studies intending to track the neurobiological trajectory using ultra-high field (7T) imaging starting from a drug-naïve first episode state. Here, we report the initial findings from the structural covariance of grey matter volume. To our knowledge, this is the first structural covariance analysis being reported using a 7T anatomical MRI acquisition.MethodsWe used ultra-high field (7 Tesla) MRI in 28 patients with FEP (satisfying criterion A of DSM-5 schizophrenia) and 18 controls, to estimate grey matter volume in a voxelwise manner. FEP and controls were matched for age, sex and parental socioeconomic status. Patients were recruited at an early intervention unit (PEPP, London Ontario) and had active psychotic symptoms at the time of scanning. Morphometric analysis was done using SPM12, after DARTEL based registration and segmentation but without spatial smoothing on 160 brain regions (6mm spheres) obtained using Dosenbach’s atlas. Correlation matrix for each group was constructed from 160*160 pearson correlation coefficients, followed by estimation of a bias matrix for each subject using jack-knife bias estimation. Bias values for each pair of nodes in an individual subject quantified the contribution of that subject to the overall within-group covariance. Higher positive values meant greater covariance between the two given nodes in that subject, relative to the rest of the group. These bias matrices can be considered equivalent to demeaned and normalised matrices of structural covariance. Structural covariance across all possible regional pairwise connections was tested using 2-tailed voxelwise T-test with FDR correction (p=0.05, 5% rate for false positives).ResultsPatients had a significant reduction in structural covariance affecting between right posterior insula and right precentral gyrus (within sensorimotor network, t=3.86, Hedge’s g = 1.15); between right posterior insula and left ventral prefrontal cortex (between sensorimotor and salience network, t=3.71, Hedge’s g = 1.10); and between right anterior cingulate cortex and right dorsal prefrontal cortex (between sensorimotor and default-mode network, t=3.10, Hedge’s g = 0.92). There were no pairwise connections with increased structural covariance among FEP subjects compared to healthy controls.DiscussionOur findings suggest that (1) structural covariance is disrupted even by the time of first-episode of psychosis; thus, the disruptions in morphological relationships reported in schizophrenia are not explicable by antipsychotic usage or illness duration (2) sensorimotor network regions show a predominant disruption in structural covariance, affecting morphological relationships with both salience and default mode regions. The functional and developmental plasticity of sensorimotor networks may be crucial for the early trajectory of psychosis.