Archive for the ‘Ventral tegmental area’ Category

Hey genome, why U make me stink at networking?

If only there was an allele that LESSENED the apprehensive and uncomfortable feelings I get when meeting new people.

As such negative feelings are the work of my amygdala, I’m wishing for some sort of LOSS-OF-FUNCTION allele that REDUCES the activity of neural circuits involved in the emotional processing of fear … but leaves other neural circuits untouched.

I just want something that takes the edge off new social experiences … yunno?

How about rs33977775 ? It contains a derived (as opposed to ancestral) T-allele that causes a Y135F change that disrupts the binding sites of the NPBWR1 receptor to its neuropeptide ligands (ie. LOSS-OF-FUNCTION).  Amazingly, this receptor has a restricted pattern of gene expression only among limbic circuits involved in emotion and reward processing (ie. EXPRESSED IN EMOTION PROCESSING CIRCUITS ONLY).

In their report, a team of authors measured the reactions of 126 university students to various social stimuli and report that individuals who carry one of these loss-of-function T-alleles (about 30% of the population) show a more positive response to social interactions.

“… the AT group perceived facial expressions more pleasantly than did the AA group, regardless of the category of facial expression. Statistical analysis … also showed that the AT group tended to feel less submissive to an angry face than did the AA group.”

So it seems that rs33977775 may dial down the amygdala response to social stimuli … just enough to ace the job interview, but not so much that you inappropriately hug your new boss. Nice!

Unfortunately, this SNP is not covered by 23andMe v3 and there is no report yet on linkage disequilibrium via 1000 genomes.  Since the frequency of the T-allele is low in African populations (1%) and about 10%-ish in other non-African populations, I guess the odds are that I’m an AA or AT.

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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 😦

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