Research: Sex and drugs and dopamine receptors 9/10/06. By the Wellcome Trust The DRD4 dopamine receptor is turning up in a range of human behaviours, from novelty-seeking to sexual drive.

Drawing links between genes, brains and behaviour is a fascinating exercise with potentially far-reaching social implications. Much attention has focused on the dopamine neurotransmitter, which is associated with pleasure seeking and addiction, among many behavioural traits. Evidence is accumulating that one particular dopamine receptor - DRD4 - affects a host of behavioural features, including attention deficit hyperactivity disorder (ADHD), intelligence, novelty-seeking and sexual desire.

A recent sweep of 51 candidate genes involved in neurotransmission picked out DRD4 as a small but significant risk factor for ADHD¹ - consistent with results from several other studies. A meta-analysis of studies on European and Asian populations confirmed that two particular forms (alleles) of the DRD4 gene are associated with increased risk of ADHD.²

There are also hints that DRD4 may influence intellectual ability. A study of first-year medical students at Korea University found a correlation between one DRD4 allele and low levels of novelty-seeking (as judged by questionnaires testing personality traits) and also, in males only, with academic achievement.³

Similarly, a study of two cohorts of children with ADHD, from the UK and New Zealand, found links between DRD4 alleles and intellectual performance, independent of the severity of their symptoms.⁴

A number of studies have found associations between particular personality traits or behaviours and DRD4, and with physical measures such as obesity. And a Japanese group has made an interesting contribution to the field by showing that two personality traits of horses - curiosity and vigilance - vary with DRD4 allele.⁵ (As horses cannot complete questionnaires, personality data were obtained from their trainers.)

In humans, DRD4 also seems to affect sexual behaviour. In a study of 148 nonclinical university students in Israel, particular DRD4 alleles were associated with students' 'Desire', 'Function' and 'Arousal' scores.⁶

Genetic association studies always need to be interpreted with caution, as the effects are generally small. It is also worth re-emphasising that the 'gene-behaviour' link is not simple in either direction - a gene influences many behaviours and a single behaviour is influenced by many genes. Nevertheless, these studies provide an intriguing glimpse into possible links between genes and behaviour, as well as routes into underlying biological mechanisms.

References

1 Brookes K et al. The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes . Mol Psychiatry 2006;11(10):934–53.

2 Li D et al. Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD) . Hum Mol Genet 2006;15(14):2276–84.

3 Ham BJ et al. Personality, dopamine receptor D4 exon III polymorphisms, and academic achievement in medical students . Neuropsychobiology 2006;53(4):203–9.9.

4 Mill J et al. Prediction of heterogeneity in intelligence and adult prognosis by genetic polymorphisms in the dopamine system among children with attention-deficit/hyperactivity disorder: evidence from 2 birth cohorts . Arch Gen Psychiatry 2006;63(4):462-9.

5 Momozawa Y et al. Association between equine temperament and polymorphisms in dopamine D4 receptor gene . Mamm Genome 2005;16(7):538-44.

6 Ben Zion IZ et al. Polymorphisms in the dopamine D4 receptor gene (DRD4) contribute to individual differences in human sexual behaviour: desire, arousal and sexual function . Mol Psychiatry 2006;11(8):782-6.