Genetic vulnerability, timing of short-term stress and mood regulation: A rodent diffusion tensor imaging study

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; Control: 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.