Zalsman Gil, Gutman Avihay, Shbiro Liat, Rosenan Ruth, Mann J John, Weller Aron
Child and Adolescent Division, Geha Mental Health Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University, New York, NY, USA.
Department of Psychology, Tel-Aviv University, Tel-Aviv, Israel; Department of Psychology and The Gonda Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel.
Eur Neuropsychopharmacol. 2015 Nov;25(11):2075-85. doi: 10.1016/j.euroneuro.2015.08.006. Epub 2015 Aug 21.
Early stressful life events predict depression and anxiety in carriers of specific polymorphisms and alter brain responses but brain structural phenotypes are largely unknown. We studied the interaction between short-term stress during specific time-windows and emotion-regulation using a genetic animal model of depression, the Wistar-Kyoto (WKY) rat. Brain structural alterations were analyzed using Diffusion Tensor Imaging (DTI). WKY (n=49) and Wistar (n=55) rats were divided into experimental groups: Early stress (ES): From postnatal day (PND) 27 rats were exposed to three consecutive days of stressors; Late stress (LS): From PND 44 rats were exposed to the same protocol;
No stressors. From PND 50, all animals were behaviorally tested for levels of anxiety and despair-like behaviors and then scanned. Gene×Environment×Timing (G×E×T) interactions (p=0.00022 after Hochberg correction) were found in ventral orbital cortex, cingulate cortex, external capsule, amygdala and dentate gyrus and in the emotion regulation measures. WKY showed longer immobility in forced swim test, but no effect of ES was detected. ES increased open-field anxiety-like behaviors in Wistar rats but not in WKY, possibly indicating a ceiling effect in WKY. Stress in pre-pubertal or adolescent phases in development may influence structural integrity of specific brain regions and emotion regulation behaviors depending on genetic vulnerability, consistent with a G×E×T interaction in mood dysregulation.
早期应激性生活事件可预测特定多态性携带者的抑郁和焦虑，并改变大脑反应，但大脑结构表型在很大程度上尚不清楚。我们使用抑郁的基因动物模型Wistar-Kyoto（WKY）大鼠，研究了特定时间窗内的短期应激与情绪调节之间的相互作用。使用扩散张量成像（DTI）分析大脑结构改变。将WKY（n = 49）和Wistar（n = 55）大鼠分为实验组：早期应激（ES）：从出生后第27天起，大鼠连续三天暴露于应激源；晚期应激（LS）：从出生后第44天起，大鼠接受相同方案；
无应激源。从出生后第50天起，对所有动物进行焦虑和绝望样行为水平的行为测试，然后进行扫描。在腹侧眶额皮质、扣带回皮质、外囊、杏仁核和齿状回以及情绪调节测量中发现了基因×环境×时间（G×E×T）相互作用（经过霍赫贝格校正后p = 0.00022）。WKY大鼠在强迫游泳试验中静止不动的时间更长，但未检测到ES的影响。ES增加了Wistar大鼠在旷场试验中的焦虑样行为，但对WKY大鼠没有影响，这可能表明WKY大鼠存在上限效应。发育过程中青春期前或青春期的应激可能会根据遗传易感性影响特定脑区的结构完整性和情绪调节行为，这与情绪失调中的G×E×T相互作用一致。
