Personalized Estimates of Brain Structural Variability in Individuals With Early Psychosis

Abstract

Background: Early psychosis in first-episode psychosis (FEP) and clinical high-risk (CHR) individuals has been associated with alterations in mean regional measures of brain morphology. Examination of variability in brain morphology could assist in quantifying the degree of brain structural heterogeneity in clinical relative to healthy control (HC) samples.

Methods: Structural magnetic resonance imaging data were obtained from CHR (n = 71), FEP (n = 72), and HC individuals (n = 55). Regional brain variability in cortical thickness (CT), surface area (SA), and subcortical volume (SV) was assessed with the coefficient of variation (CV). Furthermore, the person-based similarity index (PBSI) was employed to quantify the similarity of CT, SA, and SV profile of each individual to others within the same diagnostic group. Normative modeling of the PBSI-CT, PBSI-SA, and PBSI-SV was used to identify CHR and FEP individuals whose scores deviated markedly from those of the healthy individuals.

Results: There was no effect of diagnosis on the CV for any regional measure (P > .38). CHR and FEP individuals differed significantly from the HC group in terms of PBSI-CT (P < .0001), PBSI-SA (P < .0001), and PBSI-SV (P = .01). In the clinical groups, normative modeling identified 32 (22%) individuals with deviant PBSI-CT, 12 (8.4%) with deviant PBSI-SA, and 21 (15%) with deviant PBSI-SV; differences of small effect size indicated that individuals with deviant PBSI scores had lower IQ and higher psychopathology.

Conclusions: Examination of brain structural variability in early psychosis indicated heterogeneity at the level of individual profiles and encourages further large-scale examination to identify individuals that deviate markedly from normative reference data.

Keywords: brain morphology; coefficient of variation; early psychosis; heterogeneity; person-based similarity index.

Fig. 1.

Computation of the person-based similarity index. (A) The regional imaging measures (R) of each subject are concatenated into a single vector (S) representing their imaging profile for that measure set; (B) all possible pairwise correlation coefficients between the profile (Si) of each subject and that of the other subjects are calculated; (C) the person-based similarity index (PBSI) of subject_i is the average of all pairwise correlations between subject_i and all other subjects in the same group.

Fig. 2.

Regional coefficient of variation in clinical high-risk (CHR), first-episode psychosis (FEP), and healthy individuals. Panels A, B, and C visualize the coefficient of variation of each regional measure of cortical thickness, surface area, and subcortical volume in CHR-, FEP-, and healthy individuals (HI), respectively; no statistically significant effect of diagnosis was detected across groups.

Fig. 3.

Person-based similarity index (PBSI) for cortical thickness, surface area, and subcortical volume in clinical high-risk (CHR), first-episode psychosis (FEP), and healthy individuals. Violin plots of the PBSI for cortical thickness, surface area, and subcortical volume in the CHR-, FEP-, and healthy individuals. Statistically significant differences for all PBSI measures were noted between the healthy group and each of the clinical groups.

Fig. 4.

Nonverbal IQ (abstract reasoning) and psychopathology as a function of deviation from the normative person-specific similarity index (PBSI) for cortical thickness, surface area, and subcortical volumes. Left panel: Mean and SD in nonverbal IQ (abstract reasoning) of the clinical high-risk and first-episode psychosis individuals whose PBSI scores for either cortical thickness (PBSI-CT) or subcortical volume (PBSI-SV) deviated by >1.5 SD from the corresponding indices of the healthy group; Right panel: Mean and SD of the total scores of the Brief Psychiatric Rating Scale (BPRS) of the clinical high-risk and first-episode psychosis individuals whose PBSI-CT, or PBSI-SV or PBSI for surface area (PBSI-SA) deviated by >1.5 SD from the corresponding indices of the healthy group; group differences were not statistically significant. Note: PBSI-CT, blue color; PBSI-SA, green color; PBSI-SV, purple color; SD, vertical black line.