Abstract Background Stress is associated with elevated risk for overweight and obesity, especially in women. Since body mass index (BMI) is correlated with increased inflammation and reduced baseline cortisol, obesity may lead to altered stress responses. However, it is not well understood whether stress-induced changes in brain function scale with BMI and if peripheral inflammation contributes to this. Methods We investigated the subjective, autonomous, endocrine, and neural stress response in a transdiagnostic sample (N=192, 120 women, M BMI =23.7±4.0 kg/m 2 ; N=148, 89 women, with cytokines). First, we used regression models to examine effects of BMI on stress reactivity. Second, we predicted BMI based on stress-induced changes in activation and connectivity using cross-validated elastic-nets. Third, to link stress responses with inflammation, we quantified the association of BMI-related cytokines with model predictions. Results BMI was associated with higher negative affect after stress and an increased response to stress in the substantia nigra and the bilateral posterior insula ( p FWE &lt;.05). Moreover, stress-induced changes in activation of the hippocampus, dACC, and posterior insula predicted BMI in women ( p perm &lt;.001), but not in men. BMI was associated with higher baseline cortisol while cytokines were not associated with predicted BMI scores. Conclusions Stress-induced changes in the hippocampus and posterior insula predicted BMI in women, indicating that acute brain responses to stress might be more strongly related to a higher BMI in women compared to men. Altered stress-induced changes were associated with baseline cortisol but independent of cytokines, suggesting that the endocrine system and not inflammation contributes to stress-related changes in BMI.

Stress-induced brain responses are associated with BMI in women