Serum BDNF Increase After 9-Month Contemplative Mental Training Is Associated With Decreased Cortisol Secretion and Increased Dentate Gyrus Volume: Evidence From a Randomized Clinical Trial

Background In this study, we investigated whether mindfulness- and meditation-based mental training that improves stress regulation can upregulate BDNF (brain-derived neurotrophic factor), an important promoter of hippocampal neuroplasticity, and examined cortisol reduction as a mediating pathway. Methods In a randomized clinical trial, 332 healthy adults were randomly assigned to one of the 3 training cohorts or a passive control cohort. Training participants completed up to three 3-month-long modules targeting attention-based mindfulness, socio-affective skills, or socio-cognitive skills. We examined change in serum BDNF levels after each 3-month training interval; evaluated whether training effects were linked to reduced cortisol release in the long-term, diurnally, and when acutely stress-induced; and explored associations with hippocampal volume changes. Results In the combined training cohorts, BDNF increased significantly and cumulatively after 3-, 6-, and 9-month training relative to the pretraining baseline (3 month: t516 = 3.57 [estimated increase: 1353 pg/mL], 6 month: t516 = 3.45 [1557 pg/mL], 9 month: t516 = 3.45 [2276 pg/mL]; all ps < .001). After 9 months, training cohort BDNF was not higher than control cohort BDNF, which displayed unexplained variance. However, moderated mediation analysis showed that only training effects, and not control cohort BDNF change, were partially mediated by simultaneously reduced long-term cortisol release (3-month averages) measured in hair (15.1% mediation, p = .021). Individually greater BDNF increase after training correlated with more reduced long-term and stress-induced cortisol release. Moreover, greater BDNF increase after 9 months of training correlated with dentate gyrus volume increase (t108 = 2.09, p = .039). Conclusions Longitudinal contemplative training may promote a neurobiological pathway from stress reduction to increased BDNF levels to enhanced hippocampal volume. However, single serum BDNF measurements can be unreliable for assessing long-term neurotrophic effects in healthy adults. Future studies should investigate nonspecific BDNF measurement effects before considering application in preventive health care.