Streit Fabian, Haddad Leila, Paul Torsten, Frank Josef, Schäfer Axel, Nikitopoulos Jörg, Akdeniz Ceren, Lederbogen Florian, Treutlein Jens, Witt Stephanie, Meyer-Lindenberg Andreas, Rietschel Marcella, Kirsch Peter, Wüst Stefan
Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg , Mannheim , Germany .
Stress. 2014 Jul;17(4):352-61. doi: 10.3109/10253890.2014.921903. Epub 2014 Jun 16.
We have previously shown that urban upbringing and city living were associated with stress-induced activity in the amygdala and the perigenual anterior cingulate cortex (pACC). This finding might link the epidemiological risk factor "urbanicity" to neurobiological mechanisms of psychiatric disorders. However, given the heritability of stress-related phenotypes, it appears likely that genetic factors can modulate the effect of urbanicity on social stress processing. In the present exploratory study, we investigated if a functional sequence variation in the neuropeptide S receptor gene (NPSR1 rs324981) is associated with brain activation patterns under acute psychosocial stress and if it modulates the link between urbanicity and central stress processing. In animals, neuropeptide S has strong anxiolytic effects and it induces hypothalamus-pituitary-adrenal (HPA) axis activation. In humans, rs324981 was found to be associated with anxiety and stress-related phenotypes. Forty-two subjects were exposed to a psychosocial stress task for scanner environments (ScanSTRESS). While no main effect of rs324981 on amygdala and pACC activity was detected, we found a distinct interaction between rs324981 and urban upbringing modulating right amygdala responses. Moreover, right amygdala responses were significantly higher in subjects who also showed a salivary cortisol response to the stress exposure. The present finding of a gene × environment interaction further supports the view that the brain NPS system is involved in central stress regulation. This study provides first evidence for the assumption that a NPSR1 variant modulates brain activation under stress, interacting with the environmental risk factor urban upbringing.
我们之前已经表明，城市成长经历和城市生活与杏仁核及膝周前扣带回皮质（pACC）中应激诱导的活动有关。这一发现可能将流行病学风险因素“城市化”与精神疾病的神经生物学机制联系起来。然而，鉴于应激相关表型的遗传性，遗传因素似乎有可能调节城市化对社会应激处理的影响。在本探索性研究中，我们调查了神经肽S受体基因（NPSR1 rs324981）中的一个功能性序列变异是否与急性心理社会应激下的脑激活模式相关，以及它是否调节城市化与中枢应激处理之间的联系。在动物中，神经肽S具有强大的抗焦虑作用，并能诱导下丘脑 - 垂体 - 肾上腺（HPA）轴激活。在人类中，发现rs324981与焦虑和应激相关表型有关。42名受试者在扫描环境中接受了一项心理社会应激任务（ScanSTRESS）。虽然未检测到rs324981对杏仁核和pACC活动的主要影响，但我们发现rs324981与城市成长经历之间存在明显的相互作用，调节右侧杏仁核的反应。此外，在对应激暴露也有唾液皮质醇反应的受试者中，右侧杏仁核的反应明显更高。目前关于基因×环境相互作用的发现进一步支持了大脑NPS系统参与中枢应激调节的观点。本研究为以下假设提供了首个证据：NPSR1变体在应激状态下调节脑激活，并与环境风险因素城市成长经历相互作用。
