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  • BACKGROUND: Gene by environment (G×E) interaction between genetic variation in the promoter region of the serotonin transporter gene (serotonin transporter-linked polymorphic region [5-HTTLPR]) and stressful life events (SLEs) has been extensively studied in the context of depression. Recent findings suggest increased neural and endocrine stress sensitivity as a possible mechanism conveying elevated vulnerability to psychopathology. Furthermore, these G×E mediated alterations very likely reflect interrelated biological processes. METHODS: In the present functional magnetic resonance imaging study, amygdala reactivity to fearful stimuli was assessed in healthy male adults (n = 44), who were previously found to differ with regard to endocrine stress reactivity as a function of 5-HTTLPR × SLEs. Furthermore, functional connectivity between the amygdala and the hypothalamus was measured as a potential mechanism linking elevated neural and endocrine responses during stressful/threatening situations. The study sample was carefully preselected regarding 5-HTTLPR genotype and SLEs. RESULTS: We report significant G×E interaction on neural response patterns and functional amygdala-hypothalamus connectivity. Specifically, homozygous carriers of the 5-HTTLPR S' allele with a history of SLEs (S'S'/high SLEs group) displayed elevated bilateral amygdala activation in response to fearful faces. Within the same sample, a comparable G×E interaction effect has previously been demonstrated regarding increased cortisol reactivity, indicating a cross-validation of heightened biological stress sensitivity. Furthermore, S'S'/high SLEs subjects were characterized by an increased functional coupling between the right amygdala and the hypothalamus, thus indicating a potential link between neural and endocrine hyperreactivity. CONCLUSIONS: The present findings contribute to the ongoing debate on 5-HTTLPR × SLEs interaction and are discussed with respect to clinical implications.

  • We investigated subjective and hemodynamic responses towards disgust-inducing, fear-inducing, and neutral pictures in a functional magnetic resonance imaging study. Within an interval of 1 week, 24 male subjects underwent the same block design twice in order to analyze possible response changes to the repeated picture presentation. The results showed that disgust-inducing and fear-inducing scenes provoked a similar activation pattern in comparison to neutral scenes. This included the thalamus, primary and secondary visual fields, the amygdala, the hippocampus, and various regions of the prefrontal cortex. During the retest, the affective ratings hardly changed. In contrast, most of the previously observed brain activations disappeared, with the exception of the temporo-occipital activation. An additional analysis, which compared the emotion-related activation patterns during the two presentations, showed that the responses to the fear-inducing pictures were more stable than the responses to the disgust-inducing ones.

Last update from database: 04.06.25, 15:35 (UTC)