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.

压力和异常压力反应与精神分裂症谱系障碍 (SSD) 相关，但将压力与症状联系起来的大脑机制仍不清楚。在这项研究中，我们使用基于压力的功能性神经影像学任务，从临床前研究反向翻译，来检验压力威胁预期的异常皮质边缘处理与 SSD 中的精神病和情感症状相关的假设。参与者接受了一项与 MRI 兼容的踝部电击任务 (AST)，其中预计会有轻度电击的威胁。我们比较了N  = 18 名 SSD (10 M/8F) 参与者与N = 12 个社区控制 (9 M/3F)。在家庭方面的错误校正后，只有一个区域，即腹侧前扣带皮层 (vACC)，与对照组相比，激活显着降低。vACC 激活与简要精神病评定量表总分 ( r  = 0.54) 和精神病分量表 ( r  = 0.71) 测量的临床症状显着相关，与马里兰特质和州抑郁量表测量的特质抑郁呈负相关 ( r=-0.48）。在预期威胁的压力下，vACC 的激活不足可能导致对这种威胁的异常解释，从而导致 SSD 的精神病和情绪症状。这种实验范式具有转化潜力，可以识别与压力相关的精神疾病的电路级机制，从而实现更有针对性的治疗。