Individualized covariance profile of cortical morphology for auditory hallucinations in first-episode psychosis.

Neocortical phenotype of cortical surface area (CSA) and thickness (CT) are influenced by distinctive genetic factors and undergo differential developmental trajectories, which could be captured using the individualized cortical structural covariance (ISC). Disturbed patterns of neocortical development and maturation underlie the perceptual disturbance of psychosis including auditory hallucination (AH). To demonstrate the utility of selected ISC features as primal biomarker of AH in first-episode psychosis (FEP) subjects experiencing AH (FEP-AH), we employed herein a support vector machine (SVM). A total of 147 subjects (FEP-AH, n = 27; FEP-NAH, n = 24; HC, n = 96) underwent T1 -weighted magnetic resonance imaging at 3T. The FreeSurfer software suite was used for cortical parcellation, with the CSA-ISC and CT-ISC then calculated. The most informative ISCs showing statistical significance (P < 0.001) across every run of leave-one-out group-comparison were aligned according to the absolute value of averaged t-statistics and were packaged into candidate feature sets for classification analysis using the SVM. An optimal feature set comprising three CSA-ISCs, including the intraparietal sulcus, Broca's complex, and the anterior insula, distinguished FEP-AH from FEP-NAH subjects with 83.6% accuracy (sensitivity = 82.8%; specificity = 85.7%). Furthermore, six CT-ISCs encompassing the executive control network and Wernicke's module classified FEP-AH from FEP-NAH subjects with 82.3% accuracy (sensitivity = 79.5%; specificity = 88.6%). Finally, extended sets of ISCs related to the default-mode network distinguished FEP-AH or FEP-NAH from HC subjects with 89.0-93.0% accuracy (sensitivity = 88.4-93.4%; specificity = 89.0-94.1%). This study established a distinctive intermediate phenotype of biological proneness for AH in FEP using CSA-ISCs as well as a state marker of disease progression using CT-ISCs.