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. 2020 Jun 8:100:109879.
doi: 10.1016/j.pnpbp.2020.109879. Epub 2020 Jan 28.

Pre-onset sub-threshold psychotic symptoms and cortical organization in the first episode of psychosis

R J Rosengard  1 , C Makowski  2 , M Chakravarty  3 , A K Malla  4 , R Joober  4 , J L Shah  5 , M Lepage  6
Affiliations

Pre-onset sub-threshold psychotic symptoms and cortical organization in the first episode of psychosis

R J Rosengard et al. Prog Neuropsychopharmacol Biol Psychiatry. .

Abstract

Individuals with sub-threshold psychotic symptoms (STPS) are considered at clinical high risk for psychosis (CHR). Imaging studies comparing CHR and patients shortly after a first episode of psychosis (FEP) support progressive cortical thinning by illness stage. However, at least 30% of FEP patients deny pre-onset STPS, suggesting no history of CHR. This calls into question the generalizability of previous imaging findings. To better understand the physiology of early psychosis symptomology, we investigated the relationship between pre-onset STPS and cortical thickness (CT) among FEP patients, examining regional CT and structural covariance (SC). Patients (N = 93) were recruited from PEPP-Montreal, a FEP clinic at the Douglas Mental Health University Institute. The Circumstances of Onset and Relapse Schedule was administered to retrospectively identify patients who recalled at least one of nine expert-selected STPS prior to their FEP (STPS+, N = 67) and to identify those who did not (STPS-, N = 26). Age and sex-matched healthy controls (HC) were recruited (N = 84) for comparison. Participants were scanned between one and three times over the course of two years. CT values of 320 scans (143 HC, 123 STPS+, 54 STPS-) that passed quality control were extracted for group analysis. Linear mixed effects models accounting for effects of age, sex, education, and mean thickness were applied for vertex-wise, group comparisons of cortical thickness and SC. Multiple comparison corrections were applied with Random Field Theory (p-cluster = 0.001). Compared to controls, only STPS- patients exhibited significantly reduced CT in a cluster of the right ventral lateral prefrontal cortex. The vertex with the highest t-statistic within this cluster was employed as a seed in the subsequent SC analysis. After RFT-correction, STPS+ patients exhibited significantly stronger SC between the seed and right pars orbitalis compared to STPS- patients, and HC exhibited significantly stronger SC between the seed and right middle temporal gyrus compared to STPS- patients. Our results revealed patterns of SC that differentiated patient subgroups and patterns of cortical thinning unique to STPS- patients. Our study demonstrates that the early course of sub-threshold psychotic symptoms holds significance in predicting patterns of CT during FEP.

Keywords: Clinical high risk; Cortical thickness; Psychosis; Structural covariance.

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Conflict of interest statement

Declaration of Competing Interest M.L. reports grants from Otsuka Lundbeck Alliance, personal fees from Otsuka Canada, personal fees from Lundbeck Canada, grants and personal fees from Janssen, and personal fees from MedAvante-Prophase, outside the submitted work. R.J. reports receipt of grants, speaker's and consultant's honoraria from Janssen, Lundbeck, Otsuka, Pfizer, Shire, Perdue, HLS and Myelin and royalties from Henry Stewart Talks. In the last three years, A.M. reports honoraria for lectures given at conferences funded directly or indirectly by Lundbeck and Otsuka (Global) and consulting activities (e.g. research studies, advisory board participation) with Otsuka and Lundbeck Global and Canada, all unrelated to the present article. M.C. is a member of the editorial board of Progress in Neuropsychopharmacology and Biological Psychiatry.

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