The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress.
Psychoneuroendocrinology. 2010 Jan 13;
Authors: Alexander N, Osinsky R, Schmitz A, Mueller E, Kuepper Y, Hennig J
BACKGROUND: Growing evidence suggests that individual differences in HPA-axis reactivity to psychosocial stress are partly due to heritable influences. However, knowledge about the role of specific genetic variants remains very limited to date.
Since brain-derived neurotrophic factor (BDNF) not only exhibits neurotrophic actions but is also involved in the regulation of hypothalamic neuropeptides, we investigated the role of a common functional polymorphism within the BDNF gene (BDNF Val66Met) in the context of endocrine and cardiovascular stress reactivity.
METHODS: Healthy male adults (N=100) were genotyped and exposed to a standardized laboratory stress task (Public Speaking). Saliva cortisol and self-reported mood levels were obtained at 6 time points prior to the stressor and during an extended recovery period. Furthermore, heart rate reactivity as an indicator of sympathetic activation was monitored continuously during the experimental procedure.
RESULTS: We report a small, but significant effect of the BDNF Val66Met polymorphism on stress reactivity.
More precisely, carriers of the met-allele showed a significantly attenuated HPA-axis and cardiovascular reactivity to the psychosocial stressor compared to subjects with the val/val genotype.
Furthermore, the diminished physiological response in met-allele carriers was also attended by significantly lower self-reported ratings of perceived stress and nervousness.
CONCLUSION: Our findings of a diminished endocrine and cardiovascular stress response in healthy male adults is consistent with a previously published study and adds further evidence for a crucial role of the BDNF Val66Met polymorphism in the modulation of stress reactivity.
———-
Brain Derived Neutrophic Factor (BDNF) is a neurotransmitter/hormone produces by certain neurons of the nervous system. It promotes neuron survival, growth, deferentiation, and the creation of new synapses. It is important for learning and long-term memory.
BDNF, as this article indicates, also reduces perceived stress and sympathetic nervous system reactivity. It diminishes reactivity of the HPA-axis in response to stress.
BDNF comes in several varieties depending on the genes a person has. Certain variants – such as the Val66Met variant of BDNF – are much more effective in reducing perceived stress and reducing sympathetic nervous system reactivity – conferring a genetic advantage compared to other variants (which may increase one’s vulnerability to stress and mood disorders, for example).
In depression, BDNF expression is reduced. Antidepressants helps restore BDNF expression. Although it is postulated that excessive glucocorticoids reduce BDNF expression in depression, I wonder instead if pro-inflammatory cytokine signaling, instead, reduces BDNF expression in depression when signaling rearches a certain intensity, as part of triggered defensive sickness behavior.
A current problem is that there is no specific agent to improve BDNF signaling. Multiple substances and intercellular signals (e.g. estrogens) improve BDNF signaling, though with multiple other actions as well, which may or may not be clinically useful or safe.