Archive for the ‘AVPR1a’ Category
Comparisons of “healthy” vs. “disordered” genomes in psychiatry have not yet revealed sequence differences that can reliably predict the onset of mental disability. Rather, such disability seems to arise from as-yet-undetermined complex, probablistic interactions of genetic risk and environmental factors over the course of development. With this as the case, the demarcations between “healthy” and “disordered” may not be distinct, but rather fuzzy and hence unworthy of labels that give a false impression of being discrete states.
One recent paper that speaks to this issue is by Meyer-Lindenberg et al., “Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans” [doi: 10.1038/mp.2008.54]. Here, they explore genetic variation in the AVPR1A gene – a receptor for the pro-social neuropeptide vasopressin – and how it can modulate the activity of the amygdala when subjects view human faces (vs. a geometric shapes control condition). Since it is well known that the amygdala responds to a wide range of social and emotional stimuli and that activation of the amygdala can enhance or prevent the storage of such emotional or socially arousing events – and - that this process goes awry in autism and in subjects with amygdala damage (the picture above shows that patients with amygdala damage do not focus on the eyes of human faces) – the investigators have indeed focused-in on a key set of neural processes. They find the variation in the RS1 and RS3 polymorhphic sites in AVPR1a do indeed correlate with amygdala activity in healthy controls who were carefully screened for no history of mental disability. A great example of folks who carry the “healthy” label, but also the genetic risk and the neural correlates of autism.
The small neuropeptides oxytocin (OT) and arginine-vasopressin (AVP) are well known for their influence on promoting warm-and-fuzzy social behaviors in mammals. The G-protein coupled OTR and AVPR1a receptors are also the subject of much research in this area – particularly AVPR1a – since it shows differences in brain expression in polygamous vs. monogamous vole species, and also shows genetic associations with dysfunction in human social affiliation. In a recent foray into this line of research, Richard Ebstein and colleagues examine whether an individual’s willingness to give away a cache of money is related to genetic variation in the promoter of the AVPR1a. In their paper, “Individual differences in allocation of funds in the dictator game associated with length of the arginine vasopressin 1a receptor RS3 promoter region and correlation between RS3 length and hippocampal mRNA“, the researchers asked 203 college students to play the “dictator game” where, simply, one person gets a sum of money and can choose to keep it or give some of it away to the other player. Thats it. Give some of it away if you like, or just walk away with all of it, no questions asked & no consequences (your identity and the identity of the other player are masked). Amazingly, individuals actually DO give some of the money away (15% gave none of it away, 35% gave half away and 7% gave all – yes, all of it – away) … and more amazing still … those with longer stretches of microsatellite repeats at the RS1 & RS3 promoter sites in the AVPR1a gene, gave away significantly more money than individuals with shorter version of the repeats.
“Love is the answer, but while you’re waiting for the answer, sex raises some pretty interesting questions” so says Woody Allen. Indeed, whether you’re in love or lust, the tiny neuropeptide arginine vasopressin (AVP) is your pal. Recently, Thompson et al., found that AVP increases the perception of friendliness in females exposed to unfamiliar faces (‘tend and befriend’ a stranger), while lowering the perception of friendliness in males (the more typical aggressive response to a stranger). The fascinating modulatory effects of AVP on social affiliation are now better understood in light of the work of Allaman-Exertier and colleagues who explored the relationship between the AVPR1A receptors and the neural circuitry that underlie complex behaviors and feelings of amour. The paper is focused on the lateral septal area which is rich in vasopressinergic axons and contains high amounts of AVPR1A receptors. Mice that lack a particular type of vasopressin receptor, AVPR1A, for example, are impaired in the recall and recognition of social encounters – but, replacing the receptor just in the lateral septum, is enough to restore social recognition. The AVPR1A receptors mediate both excitatory and inhibitory post-synaptic effects within the septal area and thus can modulate activity in downstream centers such as the hypothalamus.
Note: this tid bit of knowledge will not assist in the fulfillment of romantic endeavors !