Serum Brain-Derived-Neurotrophic Factor 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: Contemplative training interventions involving mindfulness- and meditation-based practices promote wellbeing and may counteract neuroendocrine risk-factors for stress-related mood disorders, such as excess hypothalamic-pituitary-adrenal (HPA) axis activity and neuronal atrophy. We investigated whether mental training that improves stress-regulation can upregulate brain-derived neurotrophic factor (BDNF), an important promoter of hippocampal neuroplasticity, and examined cortisol reduction as a mediating pathway. METHODS: In a randomized clinical trial, N=332 healthy adults were randomly assigned to one of three training cohorts (TC1-3) or a passive control cohort. Training participants completed up to three 3-month long modules targeting mindfulness-based attention, socio-affective, or socio-cognitive skills. We examined change in serum BDNF levels after each 3-month training interval, tested for mediation of training effects by reduced cortisol release a) in the long-term, b) diurnally, and c) acutely stress-induced, and explored associations with hippocampal volume change. RESULTS: In multilevel modelling of the combined training cohorts, BDNF increased significantly and cumulatively after 3-, 6- and 9-month training relative to the pre-training baseline (3-month: t(516)=3.57 [est. increase: 1353pg/mL]; 6-month: t(516)=3.45 [1557pg/mL], 9-month: t(516)=3.45, [2276pg/mL]; all ps<.001). Training cohort BDNF increase after 9 months was not higher than in the control cohort, which displayed unexplained BDNF variance. However, moderated mediation analysis showed that other than the control cohort BDNF change, the training effect was mediated by simultaneously reduced long-term cortisol exposure (3-month averages) measured in hair after 3-, 6- and 9-months training (mediation: 15.1% of total effect, p=.021). Examining individual differences, greater BDNF increase after training correlated with reduced long-term and stress-induced cortisol release. Greater individual BDNF increase after 9-month training also correlated with increased dentate gyrus volume (t(108)=2.09, p=.039). CONCLUSIONS: Longitudinal contemplative training may activate a neurobiological pathway from stress reduction to increased BDNF levels to potentially enhanced hippocampal volume. However, single serum BDNF measurements lack reliability as indicators of longer-term neurotrophic action in healthy adults. Future studies should investigate non-specific measurement effects before examining potential applications for preventive healthcare.