Familial Liability to Psychosis Is Associated With Attenuated Dopamine Stress Signaling in Ventromedial Prefrontal Cortex
Familial Liability to Psychosis Is Associated With Attenuated Dopamine Stress Signaling in Ventromedial Prefrontal Cortex
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DOI：
10.1093/schbul/sbs187
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发表时间：
2014-01-01
影响因子：
6.6
通讯作者：
Myin-Germeys, Inez
中科院分区：
文献类型：
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作者：
Lataster, Johan;Collip, Dina;Myin-Germeys, Inez
目的：被诊断为精神障碍的患者及其一级亲属表现出对压力的反应性增加。理论预测，心理社会压力的经验与腹内侧前额叶和中脑边缘多巴胺神经传递。然而，虽然有证据表明精神障碍患者纹状体多巴胺处理异常，但前额叶皮层的作用仍然研究不足。本研究旨在探讨精神病家族性风险个体的腹内侧前额叶皮质（vmPFC）中应激诱导的体内多巴胺释放。方法：14名诊断为精神障碍的患者的健康一级亲属和10名对照受试者在静脉注射183.2（SD = 7.6）MBq [18F] fallypride后进行了单次动态正电子发射断层扫描（PET）。社会心理压力开始在注射后100分钟使用计算机化的心算任务与社会评价的威胁组件。使用线性化简化参考区模型分析PET数据。进行回归分析，以比较控制受试者和亲属之间的任务相关的配体位移的空间范围，并找到它是如何与社会心理压力和精神病的自我评价的经验。结果：一级亲属显示低反应性多巴胺信号在vmPFC在应激反应。主观评定的压力水平的增加与精神病经历的强度增加有关。这种影响在一级亲属中尤其明显。结论：虽然以前的研究已经假设了前额叶多巴胺功能障碍在精神病中的作用，但据我们所知，这项研究是第一项体内人体成像研究，显示了具有精神病家族风险的个体的vmPFC中的衰减（即低反应性）多巴胺应激神经调节。
Objective: Patients diagnosed with a psychotic disorder and their first-degree relatives display increased reactivity to stress. Theory predicts that experience of psychosocial stress is associated both with ventromedial prefrontal and mesolimbic dopamine neurotransmission. However, while there is evidence of aberrant striatal dopamine processing in psychotic disorder, the role of the prefrontal cortex remains under-researched. This study aimed at investigating stress-induced in vivo dopamine release in ventromedial prefrontal cortex (vmPFC) of individuals at familial risk for psychosis. Method: Fourteen healthy first-degree relatives of patients with a diagnosis of psychotic disorder and 10 control subjects underwent a single dynamic positron emission tomography (PET) scanning session after intravenous administration of 183.2 (SD = 7.6) MBq [18F] fallypride. Psychosocial stress was initiated at 100 min post-injection using a computerized mental arithmetic task with social evaluative threat components. PET data were analyzed using the linearized simplified reference region model. Regression analyses were performed to compare the spatial extent of task-related ligand displacement between control subjects and relatives and to find how it related to self-rated experiences of psychosocial stress and psychosis. Results: First-degree relatives displayed hyporeactive dopamine signaling in the vmPFC in response to stress. Increased levels of subjectively rated stress were associated with increased intensity of psychotic experiences. This effect was particularly pronounced in first-degree relatives. Conclusion: Although previous studies have hypothesized a role for prefrontal dopamine dysfunction in psychosis, this study, to our knowledge, is the first in vivo human imaging study showing attenuated (ie, hyporeactive) dopamine stress neuromodulation in vmPFC of individuals at familial risk for psychosis.