Aberrant anterior cingulate processing of anticipated threat as a mechanism for psychosis. (30th July 2021)

• Record Type: Journal Article
• Authors: Kvarta, Mark D.; Chiappelli, Joshua; West, Jeffrey; Goldwaser, Eric L.; Bruce, Heather A.; Ma, Yizhou; Kochunov, Peter; Hatch, Kathryn; Gao, Si; Jones, Aaron; O'Neill, Hugh; Du, Xiaoming; Hong, L. Elliot
• Is Part Of: Psychiatry research. Volume 313(2021)
• Publication Date: 2021-07-30
• Subjects: Schizophrenia -- Stress -- Ankle-shock -- Neuroimaging -- Functional imaging; Psychiatry -- Periodicals; Brain -- Imaging -- Periodicals; Psychiatry -- Periodicals; Diagnostic Imaging -- Periodicals; Psychiatrie -- Périodiques; Cerveau -- Imagerie pour le diagnostic -- Périodiques; 616.890754
• DOI: 10.1016/j.pscychresns.2021.111300
• Languages: English
• ISSNs: 0925-4927

Abstract

Highlights: A stressful anticipatory threat task using ankle-shock can be used during fMRI to interrogate brain areas responsible for stress and threat processing. Patients with schizophrenia spectrum disorder have deficient activation in the ventral anterior cingulate cortex during anticipated threat periods. This vACC activation significantly and robustly correlates with psychosis symptoms, and inversely correlates with trait depression measures. The association between clinical symptoms and abnormal threat-induced brain activation may represent a key biological substrate linking the deficiencies in threat anticipation and stress regulation in schizophrenia. Abstract: Stress and abnormal stress response are associated with schizophrenia spectrum disorder (SSD), but the brain mechanisms linking stress to symptomatology remain unclear. In this study, we used a stress-based functional neuroimaging task, reverse-translated from preclinical studies, to test the hypothesis that abnormal corticolimbic processing of stressful threat anticipation is associated with psychosis and affective symptoms in SSD. Participants underwent an MRI-compatible ankle-shock task (AST) in which the threat of mild electrical shock was anticipated. We compared functional brain activations during anticipatory threat periods from N = 18 participants with SSD (10 M/8F) to those from N = 12 community controls (9 M/3F). After family-wise error correction, only one region, the ventral anterior cingulate cortex (vACC), showed significantly reduced activation compared with controls. vACC activation significantly correlated with clinical symptoms measured by the Brief Psychiatric Rating Scale total score ( r = 0.54) and the psychosis subscale ( r = 0.71), and inversely correlated with trait depression measured by the Maryland Trait and State Depression scale ( r =-0.48). Deficient activation in vACC under stress of anticipated threat may lead to aberrant interpretation of such threat, contributing to psychosis and mood symptoms in SSD. This experimental paradigm has translational potential and may identify circuitry-level mechanisms of stress-related mental illness, leading to more targeted treatment.