Minzenberg Michael J, Lesh Tyler A, Niendam Tara A, Yoon Jong H, Rhoades Remy N, Carter Cameron S
Department of Psychiatry, University of California, San Francisco School of Medicine, San Francisco, CA, United States; Veterans Affairs Medical Center, San Francisco, CA, United States.
Department of Psychiatry, University of California, Davis School of Medicine, Sacramento, CA, United States.
Schizophr Res. 2014 Aug;157(1-3):19-25. doi: 10.1016/j.schres.2014.05.039. Epub 2014 Jun 24.
Suicide is highly-prevalent and the most serious outcome in schizophrenia, yet the disturbances in neural system functions that confer suicide risk remain obscure. Circuits operated by the prefrontal cortex (PFC) are altered in psychotic disorders, and various PFC changes are observed in post-mortem studies of completed suicide. We tested whether PFC activity during goal-representation (an important component of cognitive control) relates to long-term suicide risk in recent-onset schizophrenia.
35 patients with recent-onset of DSM-IV-TR-defined schizophrenia (SZ) were evaluated for long-term suicide risk (using the Columbia Suicide Severity Rating Scale) and functional MRI during cognitive control task performance. Group-level regression models associating control-related brain activation with suicide risk controlled for depression, psychosis and impulsivity.
Within this group, past suicidal ideation was associated with lower activation with goal-representation demands in multiple PFC sectors. Among those with past suicidal ideation (n=18), reported suicidal behavior was associated with lower control-related activation in premotor cortex ipsilateral to the active primary motor cortex.
This study provides unique evidence that suicide risk directly relates to PFC-based circuit dysfunction during goal-representation, in a major mental illness with significant suicide rates. Among those with suicidal ideation, the overt expression in suicidal behavior may stem from impairments in premotor cortex support of action-planning as an expression of control. Further work should address how PFC-based control function changes with risk over time, whether this brain-behavior relationship is specific to schizophrenia, and address its potential utility as a biomarker for interventions to mitigate suicide risk.
自杀在精神分裂症中极为普遍且是最严重的后果，但导致自杀风险的神经系统功能障碍仍不清楚。前额叶皮质（PFC）所操控的神经回路在精神障碍中会发生改变，并且在自杀身亡者的尸检研究中观察到了各种PFC变化。我们测试了目标表征（认知控制的一个重要组成部分）过程中的PFC活动是否与近期发病的精神分裂症患者的长期自杀风险相关。
对35例近期发病的DSM-IV-TR定义的精神分裂症（SZ）患者进行了长期自杀风险评估（使用哥伦比亚自杀严重程度评定量表），并在认知控制任务执行过程中进行了功能磁共振成像。将与控制相关的大脑激活与自杀风险相关联的组水平回归模型对抑郁、精神病和冲动性进行了控制。
在该组患者中，过去的自杀意念与多个PFC区域中目标表征需求下较低的激活有关。在有过去自杀意念的患者（n = 18）中，报告的自杀行为与主动初级运动皮层同侧的运动前皮层中较低的控制相关激活有关。
本研究提供了独特的证据，即在自杀率较高的一种主要精神疾病中，自杀风险直接与目标表征过程中基于PFC的神经回路功能障碍有关。在有自杀意念的患者中，自杀行为的明显表现可能源于运动前皮层对作为控制表达的行动计划支持的受损。进一步的研究应探讨基于PFC的控制功能如何随时间风险而变化，这种脑-行为关系是否特定于精神分裂症，并探讨其作为减轻自杀风险干预生物标志物的潜在效用。
