Rasetti Roberta, Mattay Venkata S, Wiedholz Lisa M, Kolachana Bhaskar S, Hariri Ahmad R, Callicott Joseph H, Meyer-Lindenberg Andreas, Weinberger Daniel R
Genes, Cognition, and Psychosis Program, IRP, NIMH, NIH, Rm. 4S-235, 10 Center Dr., Bethesda, MD 20892, USA.
Am J Psychiatry. 2009 Feb;166(2):216-25. doi: 10.1176/appi.ajp.2008.08020261. Epub 2008 Dec 15.
Although amygdala dysfunction is reported in schizophrenia, it is unknown whether this deficit represents a heritable phenotype that is related to risk for schizophrenia or whether it is related to disease state. The purpose of the present study was to examine amygdala response to threatening faces among healthy siblings of schizophrenia patients in whom a subtler heritable deficit might be observed.
Participants were 34 schizophrenia patients, 29 unaffected siblings, and 20 healthy comparison subjects. Blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was conducted during an implicit facial information processing task. The N-back working memory task, which has been shown to elicit prefrontal cortex abnormalities in unaffected siblings of schizophrenia patients, was employed as a positive experimental control.
Schizophrenia patients demonstrated a deficit in amygdala reactivity to negative face stimuli and an alteration, correlated with neuroleptic drug dosage, in the functional coupling between the amygdala and subgenual cingulate. In contrast, unaffected siblings showed a pattern that was not statistically different from that of healthy comparison subjects. During the N-back working memory task, both schizophrenia patients and their unaffected siblings demonstrated a pattern of inefficient prefrontal cortex engagement, which is consistent with earlier evidence that this pattern is related to genetic risk for schizophrenia.
These data suggest that the pathophysiological mechanism underlying the inability of individuals with schizophrenia to normally engage the amygdala in processing fearful and angry facial representations is more likely a phenomenon related to the disease state, specifically to treatment.
尽管精神分裂症患者杏仁核功能异常已有报道，但尚不清楚这种缺陷是否代表与精神分裂症风险相关的可遗传表型，还是与疾病状态有关。本研究的目的是检查精神分裂症患者健康同胞中杏仁核对威胁性面孔的反应，在这些同胞中可能观察到更细微的遗传缺陷。
参与者包括34名精神分裂症患者、29名未患病的同胞和20名健康对照者。在一项内隐面部信息处理任务期间进行了血氧水平依赖（BOLD）功能磁共振成像（fMRI）。N-back工作记忆任务已被证明能在精神分裂症患者未患病的同胞中引发前额叶皮质异常，被用作阳性实验对照。
精神分裂症患者对负面面部刺激的杏仁核反应性存在缺陷，且杏仁核与膝下扣带回之间的功能耦合发生改变，这种改变与抗精神病药物剂量相关。相比之下，未患病的同胞表现出与健康对照者无统计学差异的模式。在N-back工作记忆任务期间，精神分裂症患者及其未患病的同胞均表现出前额叶皮质参与效率低下的模式，这与早期证据一致，即这种模式与精神分裂症的遗传风险有关。
这些数据表明，精神分裂症患者无法正常使杏仁核参与处理恐惧和愤怒面部表征的病理生理机制更可能是一种与疾病状态相关的现象，特别是与治疗有关。
