The serotonin transporter gene variants modulate acute stress-induced hippocampus and dorsomedial prefrontal cortex activity during memory retrieval.

The short (s) allele of a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is related to reduced serotonin transporter efficiency and an increased vulnerability to stress and mental disorders. In the present study, we investigated how 5-HTTLPR impacts on memory retrieval under stress and related neural activity by reanalyzing a small genetic neuroimaging data set. Twenty-seven healthy male volunteers participated in both the Trier Social Stress Test (TSST) and a respective control procedure and then their brain activity was measured with functional MRI (fMRI) while they performed an emotional-face-recognition task. Sixteen participants were carriers of the short allele (ss/sl carriers) and 11 were homozygous for the long allele (ll carriers). Genotype groups were compared with respect to stress-related physiological changes, memory performance, and brain activity. No significant genotype-dependent effects on memory performance or cortisol levels were found. The ss/sl carriers showed significantly higher systolic and diastolic blood pressure than the ll carriers, independent of stress. The ss/sl carriers reported stronger stress-induced nervous mood than the ll carriers. Our fMRI data revealed that the ss/sl carriers showed significantly weaker left hippocampus activation and stronger dorsomedial prefrontal cortex (dmPFC) deactivation when retrieving memories under stress as compared with the ll carriers. Subsequent analyses revealed that the distinct hippocampal activation pattern in both genotypes was associated with stress-induced cortisol elevation, while the distinct dmPFC activation pattern in both genotypes was associated with stress-induced changes in reaction times. Our results thus add new evidence that serotonin signaling modulates neural activity in the hippocampus and dmPFC during memory retrieval under acute psychosocial stress.