24 October 2009

Fascinating Recent History of NOS1 Variant

In January of 2009, Neuroskeptic blog was reporting on a study in Archives of General Psychiatry that painted NOS1 Ex1f variant as "an impulsivity gene." Apparently the January 2009 study included brain imaging, which suggested that normal prefrontal inhibition of activity was somehow impaired in persons with the NOS1 variant studied. Pairing the January 2009 AGP study with the more recent October 2009 AGP study suggests a tangible link between impulsivity and cognition -- via the NOS1 gene.
NOS1 codes for the enzyme nitric oxide synthase 1, which is expressed in neurones and makes nitric oxide (Nitrogen monoxide, NO). NO is a small molecule with various roles in animals, most famously the ability to induce erections - Viagra works by enhancing this effect. NO is also known to act as a neurotransmitter, with widespread but poorly understood functions in the brain. It's therefore plausible that altered nitric oxide synthase function could affect behaviour, and several animal studies suggest that indeed it does.

...In two separate control samples of normal German adults (most of whom) were screened to exclude psychiatric disorders (n=640 and 1314), 21 and 20% carried two copies of the short allele (SS). I've helpfully highlighted that in green above. Then, in samples of German people who displayed various forms of impulsive behaviour, the SS genotype was more common: in 383 adults with ADHD (28% SS), 189 adults who had attempted suicide (25% SS), and adults with "Cluster B" personality disorders 26% SS, but not those with "Cluster C" disorders representing anxious traits. Also, in a sample of 182 criminals referred to a forensic psychiatry unit, those who had been assessed as "violent" were more likely to carry the SS genotype than those not (p=0.04). In a nutshell, SS is bad. _Neuroskeptic
A lot of researchers are likely to make their careers on this one gene variant. NOS1 may prove to be a very important gene for both cognition and behaviour. It is unlikely to be the most important gene involved in thinking, feeling, and acting, but it seems to be important enough.

In the 12 years since this polymorphism has attracted more attention than any other in the field of behavioural genetics with several hundred papers at last count. So if that's anything to go by, we'll be hearing a lot more about NOS1. Stay tuned. Neuroskeptic

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