41.2 THE EFFECTS OF DEVELOPMENTAL STRESS AND TRAUMA ON THE DOPAMINE SYSTEM
41.2 THE EFFECTS OF DEVELOPMENTAL STRESS AND TRAUMA ON THE DOPAMINE SYSTEM
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41.2 发育应激和创伤对多巴胺系统的影响
DOI：
10.1093/schbul/sbz022.170
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发表时间：
2019
影响因子：
6.6
通讯作者：
Bloomfield M
中科院分区：
文献类型：
--
作者：
Bloomfield M
背景暴露于发展性心理应激源、逆境和创伤会增加精神病的风险。越来越多的证据表明，发育压力和创伤会引起多巴胺能功能的长期变化，这可能会导致潜在的精神疾病。因此，我将提出一个现有的人类和动物文献的综合研究如何发展的创伤和压力改变多巴胺能功能在成年期。此外，我将介绍一项研究的结果，使用正电子发射断层扫描（PET）的多巴胺合成能力和急性应激反应的健康成年人暴露于发展和成人心理社会逆境。方法：我们对动物和人类文献进行了系统的回顾，使用了三个上位概念，包括“童年”，“创伤”和“多巴胺”的术语。PET研究采用病例对照设计（每组n=17），其中一组暴露于高水平的发育和成人心理社会逆境，另一组暴露于低水平。使用蒙特利尔压力任务诱导急性心理压力。结果共纳入140篇文献。发育应激和创伤导致关键认知领域的多巴胺能功能发生长期、复杂的变化，包括纹状体多巴胺能反应对应激源的敏感化和额叶多巴胺能功能减退。多巴胺能功能的不同变化取决于发育暴露的时间，可能代表关键时期。发育应激暴露增强多巴胺能处理的各个方面，包括腹侧（边缘）纹状体中与威胁相关的信号放大。这可能与杏仁核中的多巴胺能钝化同时发生，导致恐惧消退缺陷，从而损害区分安全与不安全环境的能力。在我们的PET实验中，在没有精神病的人中，长期的心理社会逆境与基线多巴胺合成能力降低以及纹状体多巴胺和急性应激反应之间的解偶联有关。结论发展性创伤暴露可能通过在奖赏、威胁和执行加工中产生持久的变化而诱发潜在的精神病易感性。需要进一步的研究来调查创伤诱导的多巴胺能功能变化如何诱导精神病易感性的确切机制，以及多巴胺能过程如何赋予恢复力。
Background Exposure to developmental psychological stressors, adversity and trauma increases the risk of psychosis. Converging evidence indicates that developmental stress and trauma induce long-term changes in dopaminergic functioning which could give rise to a latent vulnerability to mental illness. I will therefore present a synthesis of the existent human and animal literature examining how developmental trauma and stress alters dopaminergic functioning in adulthood. In addition, I will present results of a study using positron emission tomography (PET) of dopamine synthesis capacity and the acute stress response in healthy adults exposed to developmental and adult psychosocial adversity. Methods We conducted a systematic review of the animal and human literature using a combination of three superordinate concepts including ‘childhood’, ‘trauma’ and ‘dopamine’ terms. The PET study used [18F]-DOPA in a case-control design (n=17 per group), with one group exposed to high levels of developmental and adult psychosocial adversity and another group exposed to low levels. Acute psychological stress was induced using the Montreal Stress Task. Results 140 studies were included in our review. Developmental stress and trauma results in long-term, complex changes in dopaminergic function across key cognitive domains including sensitization of the striatal dopaminergic response to stressors and frontal hypodopaminergia. Divergent alterations in dopaminergic function occurred depending on the timing of developmental exposure potentially representing critical periods. Developmental stress exposure potentiates aspects of dopaminergic processing including amplifying threat-related signaling in the ventral (limbic) striatum. This may occur alongside dopaminergic blunting in the amygdala resulting in deficits in fear extinction, impairing the ability to distinguish safe from unsafe environments. In our PET experiment, within people without psychosis long-term psychosocial adversity was associated with reduced baseline dopamine synthesis capacity and de-coupling between striatal dopamine and the acute stress response. Conclusions Developmental trauma exposure is likely to be inducing latent vulnerability to psychosis by producing lasting changes in reward, threat and executive processing. Further studies are needed to investigate the precise mechanisms underlying how trauma-induced changes in dopaminergic function induce vulnerability to psychosis and, in parallel, how dopaminergic processes may confer resilience.