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Cortical Abnormalities in Youth at Clinical High-Risk for Psychosis: Findings From the NAPLS2 Cohort

Cortical Abnormalities in Youth at Clinical High-Risk for Psychosis: Findings From the NAPLS2 Cohort

Yoonho Chung et al. Neuroimage Clin.

Abstract

In a recent machine learning study classifying "brain age" based on cross-sectional neuroanatomical data, clinical high-risk (CHR) individuals were observed to show deviation from the normal neuromaturational pattern, which in turn was predictive of greater risk of conversion to psychosis and a pattern of stably poor functional outcome. These effects were unique to cases who were between 12 and 17 years of age when their prodromal and psychotic symptoms began, suggesting that neuroanatomical deviance observable at the point of ascertainment of a CHR syndrome marks risk for an early onset form of psychosis. In the present study, we sought to clarify the pattern of neuroanatomical deviance linked to this "early onset" form of psychosis and whether this deviance is associated with poorer premorbid functioning. T1 MRI scans from 378 CHR individuals and 190 healthy controls (HC) from the North American Prodrome Longitudinal Study (NAPLS2) were analyzed. Widespread smaller cortical volume was observed among CHR individuals compared with HC at baseline evaluation, particularly among the younger group (i.e., those who were 12 to 17 years of age). Moreover, the younger CHR individuals who converted or presented worsened clinical symptoms at follow-up (within 2 years) exhibited smaller surface area in rostral anterior cingulate, lateral and medial prefrontal regions, and parahippocampal gyrus relative to the younger CHR individuals who remitted or presented a stable pattern of prodromal symptoms at follow-up. In turn, poorer premorbid functioning in childhood was associated with smaller surface area in medial orbitofrontal, lateral frontal, rostral anterior cingulate, precuneus, and temporal regions. Together with our prior report, these results are consistent with the view that neuroanatomical deviance manifesting in early adolescence marks vulnerability to a form of psychosis presenting with poor premorbid adjustment, an earlier age of onset (generally prior to the age of 18 years), and poor long-term outcome.

Keywords: Brain development; Clinical high risk; Magnetic resonance imaging; Premorbid functioning; Psychosis; Schizophrenia.

Figures

Fig. 1
Fig. 1
In the upper panels, mean cortical thickness of NAPLS2 healthy controls is plotted as a function of age before (upper left) and after (upper right) adjusting for the scanner offsets. The solid lines represent least-square linear fits and the colors correspond to different scanners used. In the lower panels, mean cortical thickness of human traveler subjects are plotted across selected scanners. (Lower left) Mean cortical thickness before adjusting for scanner offsets. (Lower right) Mean cortical thickness after adjusting for the offsets. Colors and shape correspond to human phantom ID and scan time points, respectively.
Fig. 2
Fig. 2
Frequency distribution of between-site ICCs both before and after adjusting for the scanner offsets across all neuroanatomical Desikan based ROIs and subcortical segmentations.
Fig. 3
Fig. 3
GAM fitted age trajectories of total cortical gray matter volume, surface area, and mean thickness for individuals at CHR (n = 428) and healthy controls (n = 205). Shaded regions represent 95% confidence interval.
Fig. 4
Fig. 4
Statistical P-value maps showing clusters in which individuals at CHR (n = 378) show significantly smaller cortical volume, surface area, and cortical thickness compared to healthy controls (n = 190). Regions exhibiting smaller cortical measures in CHR individuals than healthy controls are represented with a cooler color scheme. The effect was corrected for multiple comparisons by z Monte Carlo simulations and thresholded at P < .05. Uncorrected P values were displayed within the thresholded clusters.
Fig. 5
Fig. 5
Differences in cortex volume, surface area, and cortical thickness between CHR-Stable/Remitted (n = 87), CHR-Decline (n = 59), and healthy controls (n = 52) who are 17 years of age or under. P-values for post-hoc pairwise t-tests are indicated (uncorrected). *P < .05, **P < .01 *** P < .001.
Fig. 6
Fig. 6
Differences in cortex volume, surface area, and cortical thickness between individuals with poor (n=87) versus good (n=111) premorbid functioning among those who are 17 years of age or under (CHR and control individuals combined). P-values for post-hoc pairwise t-tests are indicated (uncorrected). **P < .01 *** P < .001.

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