Archive for the ‘DRD4’ Category

A stable relationship with a nice loyal guy AND a secret wild fling with a swarthy promiscuous guy?  Admit it … you’ve probably been there, done that.

From: Associations between Dopamine D4 Receptor Gene Variation with Both Infidelity and Sexual Promiscuity

“Worldwide median rates of non-paternity, or the rate of men raising children under the pretense of biological parentage, have been suggested to near 9%, or 10% more popularly.”

If the 3rd exon in your dopamine D4 receptor (DRD4) gene carries 7-repeats of a 48-nucleotide sequence (48bp VNTR), then you may be slightly more like Snookie and her booze-addled kooka than you wish to admit.

“The dopaminergic reward pathway influences physiological arousal, pleasure, and intrinsic reward. Humans that possess at least one allele 7-repeats or longer (7R+) display behavioral phenotypes associated with attention deficit hyperactivity disorder (ADHD), alcoholism, financial risk-taking, disinhibition and impulsivity, and sexual behavior.”

But don’t blame it all on your genes.  Your environment can modulate your genetic proclivities.

“In r-selected environments (i.e., unpredictable and unstable environments, where the ability to mate more and produce more offspring is favored), 7R+ genotype would be expected to rise in frequency. That is, in environments where “cad” behavior is adaptive, selective pressure for 7R+ would be positive; but in environments where “dad” behavior is adaptive, selective pressure for 7R+ would be negative. This is consistent with the dramatic differences in DRD4 VNTR allele frequencies and behavioral patterns found globally such as in the generally polygamous and agonistic Yanomamö Indians of South America (high 7R+ frequencies) and the generally egalitarian !Kung of the Kalahari (low 7R+ frequencies).”

I’m a DRD4 double fist pumping 7R/7R … so, like, I guess … that explains a lot of the skeletons in my closet.

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Political power must feel pretty good … especially if you have deep-seated personal insecurities and can conveniently use the notoriety of your office to indulge in a sense of superiority and vanity.  Among many, many brain systems that develop slowly during childhood – inflated ego, interpersonal hostility and impulsivity can emerge very early during development.  Instantaneous electronic “boner-to-picture-to-internet” hand-held technology just makes it that much easier to get busted once you’ve become a full-grown asshole.

Here’s a small insight into how this unfortunate developmental pathway might unfold … from a small-scale genetic study on variation in an intra-cytoplasmic loop of the Dopamine DRD4 receptor and its relationship to infidelity:

[DRD4] 7R+ individuals exhibit augmented anticipatory desire response to stimuli signaling dopaminergic incentives, such as food, alcohol, tobacco, gambling, and opiates. Although it is as yet speculative, these associations suggest that 7R+ individuals may allocate greater attention to appetitive rewards, contributing to the behavioral differences in promiscuity and infidelity observed here.

Neither the first, nor the last gene-twitter interaction to have gone badly for someone …

More on the DRD4 and social bonding genes

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Dopamine receptor D4
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Attention Deficit Hyperactivity Disorder is one of the most widespread psychiatric diagnoses in children. Parents who are faced with the decision to medicate or not medicate their children may wonder if their child – given a bit more time – won’t just “grow out of it”, as many children seem to do. With this in mind, it would obviously be helpful to have biomarkers that could predict whether certain children are more likely to simply acquire better attentional control on their own, and those children that might not. In their paper, “Polymorphisms of the Dopamine D4 Receptor, Clinical Outcome, and Cortical Structure in Attention-Deficit/Hyperactivity Disorder” (Arch Gen Psychiatry Vol 64 (no. 8), Aug 2007) a veritable dream team of child developmental neuroscientists working across several medical institutions report on two such biomarkers. One biomarker is the thickness of the orbitofrontal cortex and posterior parietal cortex. MRI-based measurments of these parts of the brain (just about 5mm thick!) show that children who carry a diagnosis of ADHD have a thinner cortical sheet in these regions. Another biomarker is genetic variation in an intracytoplasmic loop of the G-protein coupled dopamine D4 receptor (DRD4). Children with ADHD are more likely to carry a longer 7-repeat version of this VNTR polymorphism than the more common 4-repeat. Interestingly, the research team found that healthy children who carry the 7-repeat genetic variant also have slightly thinner cortex in the orbitofrontal and posterior parietal cortex, suggesting that this genetic variant may influence the risk of ADHD by way of an effect on cortical development. Additionally, the research team found that the cortex of ADHD children who carry this 7-repeat genetic variant “catches up” from age 8 and eventually falls within the range of healthy children by age 15. Lastly, the team reports that ADHD children who carry the 7-repeat had better clinical outcomes (albeit, many of the ADHD children in this study were treated with medication). Nevertheless, it appears that some progress has been made in identifying biomarkers that might predict favorable developmental trajectories.

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The publication of positive genetic association results is always something to cheer about although most of us know that on a different day, with a different sample, the results could just as easily been flat. So when a meta-analytical paper appears that actually supports a previous finding, you have to savor the sweet joy of it. So it is that Marcus Munafo and colleagues under the leadership of Jonathan Flint – one of the best meta-analytical assessors in the biz – report that the “C” allele of rs1800955 in the dopamine d4 receptor (DRD4) gene (doi: 10.1016/j.biopsych.2007.04.006) survives an analysis of several dozen studies on genetics and personality. Although small, “The evidence from our final meta-analysis indicatest hat the true effect size of the C-521T polymorphism on novelty seeking and impulsivity traits, if genuine, may account for up to 3%o of phenotypic variance.” I, perhaps due to my “C” allele am excited !

MUNAFO, M. (2008). Association of the Dopamine D4 Receptor (DRD4) Gene and Approach-Related Personality Traits: Meta-Analysis and New Data. Biological Psychiatry, 63(2), 197-206. DOI: 10.1016/j.biopsych.2007.04.006

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