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

Biol Psychiatry Glob Open Sci. 2024 Nov 10;5(2):100414. doi: 10.1016/j.bpsgos.2024.100414. eCollection 2025 Mar.

Abstract

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: t 516 = 3.57 [estimated increase: 1353 pg/mL], 6 month: t 516 = 3.45 [1557 pg/mL], 9 month: t 516 = 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 (t 108 = 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.

Keywords: BDNF; Cortisol; Hippocampus; Meditation; Mindfulness-based training; Stress reduction.

Plain language summary

We examined whether meditation-based mental training that reduces psychological stress can increase BDNF (brain-derived neurotrophic factor), a protein that supports brain health. In a randomized trial, 332 adults underwent up to 9 months of training focused on attention-based mindfulness and affective and cognitive skills, or were assigned to a control condition. Results showed significant increases in BDNF over training time, mediated by reduced long-term secretion of the stress hormone cortisol. Increased BDNF was also linked to greater dentate gyrus volume of the hippocampus. However, unexpected BDNF changes in the control condition limit the conclusions that can be drawn. While promising, the findings also highlight the need for more reliable BDNF measures before applying these results to preventive health care.