Monoaminergic variation, cortical structure, and disaster trauma interact to shape emotional vulnerability

Emotional vulnerability arises from the interplay of genetic variation, cortical network capacity, and subjective processing of adverse experiences, yet these components are rarely examined together in population-scale datasets. Monoaminergic signaling offers an opportunity for understanding such interactions because variation in related genes shapes sensitivity to environmental inputs. Among them, the vesicular monoamine transporter 1 (VMAT1) Thr136Ile variant is notable for its functional effects and its long-term maintenance at intermediate frequencies, a pattern consistent with context-dependent selection. These properties make it an informative marker for investigating how genetic sensitivity interacts with neurobiological and experiential factors to shape affective functioning. Using data from up to 9,625 participants in the Tohoku Medical Megabank Project, a cohort established after the 2011 Great East Japan Earthquake, we investigated how monoaminergic variation, cortical morphology, and traumatic memory shape affective functioning. We found associations between the Thr136Ile variant and negative affectivity and depressive symptoms, consistent with prior reports of heightened emotional reactivity associated with the 136Thr allele. However, magnitude of these effects was substantially amplified in specific experiential and neurobiological contexts. Subjective trauma sensitivity, capturing the discrepancy between earthquake disruption and current traumatic memory, displayed a genotype-dependent association with depressive symptoms, and this relationship was strongest when parietal or insular cortical surface area was smaller. Together, these results identify a multilevel pathway through which monoaminergic variation contributes to emotional vulnerability by interacting with both cortical network capacity and trauma processing. The context-dependent influence of monoaminergic variation may further contribute to maintenance of affective diversity in human populations.