Abstract
Schizophrenia has been extensively associated with reduced cortical thickness (CT), and its neurodevelopmental origin is increasingly acknowledged. However, the exact timing and extent of alterations occurring in preclinical phases remain unclear. With a high prevalence of psychosis, 22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder that represents a unique opportunity to examine brain maturation in high-risk individuals. In this study, we quantified trajectories of CT maturation in 22q11DS and examined the association of CT development with the emergence of psychotic symptoms. Longitudinal structural MRI data with 1–6 time points were collected from 324 participants aged 5–35 years (N = 148 22q11DS, N = 176 controls), resulting in a total of 636 scans (N = 334 22q11DS, N = 302 controls). Mixed model regression analyses were used to compare CT trajectories between participants with 22q11DS and controls. Further, CT trajectories were compared between participants with 22q11DS who developed (N = 61, 146 scans), or remained exempt of (N = 47; 98 scans) positive psychotic symptoms during development. Compared to controls, participants with 22q11DS showed widespread increased CT, focal reductions in the posterior cingulate gyrus and superior temporal gyrus (STG), and accelerated cortical thinning during adolescence, mainly in frontotemporal regions. Within 22q11DS, individuals who developed psychotic symptoms showed exacerbated cortical thinning in the right STG. Together, these findings suggest that genetic predisposition for psychosis is associated with increased CT starting from childhood and altered maturational trajectories of CT during adolescence, affecting predominantly frontotemporal regions. In addition, accelerated thinning in the STG may represent an early biomarker associated with the emergence of psychotic symptoms.
Highlights
In recent years, considerable research efforts in schizophrenia have provided extensive support for a neurodevelopmental origin of the illness involving altered gray matter structure
Notable exceptions were observed in the bilateral posterior cingulate cortex (PCC) and superior temporal gyrus (STG), where cortical thickness (CT) was significantly lower in participants with 22q11DS compared to controls
Cluster peaks of altered developmental trajectories were predominantly found in frontotemporal regions including the left rostral middle, superior frontal, lateral orbitofrontal gyri, right paracentral, and bilateral precentral gyri as well left middle temporal, fusiform, and parahippocampal regions and the right inferior temporal gyrus
Summary
Considerable research efforts in schizophrenia have provided extensive support for a neurodevelopmental origin of the illness involving altered gray matter structure. Findings suggest that structural alterations appear in a progressive manner, with milder gray matter reductions in individuals at clinical high risk and gradually more aggravated differences in patients with first-episode psychosis and chronic schizophrenia [4, 8, 9]. Prospective studies on ultra-high-risk individuals have emerged to address this question and have shown steeper rates of cortical thinning in individuals who eventually convert to psychosis, affecting frontotemporal regions [9,10,11], as well as cingulate, parietal and insular areas [11]. Studies investigating ultra-high-risk individuals have been limited by their number of follow-up scans (e.g., 1 follow-up) and did not assess neurodevelopment in at-risk individuals before the onset of psychotic symptoms
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