Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis

Abstract

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Schizophrenia polygenic risk during typical development reflects multiscale cortical organization

“…Longitudinal data and case-control meta-analysis have shown that the development of psychosis in high-risk adolescents is associated with progressive loss of cortical thickness in several areas of the association cortex [18,72]. Of note, the areas implicated in these studies overlap considerably with those showing increased cortical thickness in early childhood and more pronounced cortical thinning in adolescents with higher PRS-SCZ in the current study.…”

“…We observed that the PRS-SCZ effects on cortical thickness appear to be transient and disappear with cortical maturation in typically developing children and adolescents; however, we presume that they may persist or worsen in the presence of other biological and environmental risk factors. Several longitudinal and case-control studies have shown that the development of psychosis in high-risk adolescents is associated with progressive loss of cortical thickness in several areas of association cortex (Pantelis et al ., 2003; Cannon et al ., 2015; ENIGMA Clinical High Risk for Psychosis Working Group et al ., 2021). Of note, the areas implicated in these studies overlap considerably with those showing increased cortical thickness with higher PRS-SZ here.…”

“…Schizophrenia-related genes are implicated in neurodevelopmental processes and as such the effect of PRS-SCZ on cortical thickness likely varies with age. Although the cross-sectional nature of this cohort prohibits mapping individual trajectories of cortical development, we sought to approximate developmental variation in the effect of PRS-SCZ by estimating age group effects of early childhood (3-9 yrs), early adolescence (10-15 yrs), and late adolescence (15)(16)(17)(18)(19)(20)(21) in the cohort. Higher PRS-SCZ was associated with greater cortical thickness in early childhood, however the pattern differs in the older age groups (Figure 5).…”

“…The neurodevelopmental hypothesis of schizophrenia posits that cortical maturation is perturbed, producing widespread cortical abnormalities [15]. Differences in cortical morphometry are consistently reported across different stages and clinical phenotypes of the schizophrenia spectrum [16][17][18]. Investigating neurodevelopmental features of schizophrenia requires a departure from classic case-control designs, however.…”

Neuroanatomical markers of psychotic experiences in adolescents: A machine-learning approach in a longitudinal population-based sample

“…Significant impairments in receptive language scores and microstructural changes in the arcuate fasciculus, a language-related white matter tract connecting the inferior frontal gyrus, were previously reported in this cohort of adolescents with PEs at 11–13 years ( Blanchard et al, 2010 , Dooley et al, 2020 ). Accelerated frontal lobe cortical thinning has been observed in adolescents who developed depressive symptoms ( Bos et al, 2018 ), in externalising behaviours in adolescents ( Tanzer et al, 2020 ) and in adolescents at chronic high risk of psychosis ( Cannon et al, 2015 , ENIGMA Clinical High Risk for Psychosis Working Group et al, 2021 , Jung et al, 2011 ). Other robust frontal cortical regions classifying the 18–20 year old group included the left superior frontal cortex and left orbitofrontal cortex.…”