Genes 2 Brains 2 Mind 2 Me

It’s generally not fun to be browbeaten, bullied, bulldozed or downright oppressed – by the schoolyard bully or perhaps the micromanaging boss – in any form. While we’ve all been there – sometimes with initial feelings of sorrow, mopiness, lethargy, etc. – all part of the normal adaptive response to just pack-it-in and withdraw, the effects of social stress in some individuals can be quite profound and serious. The recent paper, “Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions” by Krishnan and company (DOI) provides some insight into mechanisms of social stress and how several genetic factors are implicated in the regulation of activity of a particular synapse linking the ventral tegmental area (VTA) and nucleus accumbens (NAc). Of particular interest is the protective effect of a single G to A nucleotide change (rs6265) in the brain derived neurotrophic factor (BDNF) that leads to a valine to methionine amino acid substitution at position 66, a portion of the protein thought to play a role in cytoplasmic trafficking. As reported, transgenic mice that carry the human form of the poorly secreted Met/Met form of BDNF did not suffer a typical withdrawl, depression-like syndrome when subjected to a paradigm of chronic social defeat as compared to defeated Val/Val (highly secreted form) mice. In correspondence with this finding, higher levels of BDNF were found in the NAc in human cases of human depression. The authors’ work provides a new mechanistic model for regulation of VTA-NAc synaptic activity that makes testable predictions about complex behaviors and avenues for prevention and remediation of one of life’s unpleasant, but inevitable, tribulations.

…darn-it !  my 23andMe profile shws that I am a C/C valine/valine … how depressing 😦