Possible involvement of the dopamine D3 receptor locus in subtypes of bipolar affective disorder

The dopamine D3 receptor gene is of potential interest in the physiopathology of affective disorder because of its expression pattern in brain structures controlling various aspects of behaviour, cognition and emotions. Moreover, it encodes for a receptor protein that is a target for psychotropic drugs, which turn out to be efficient in the treatment of this disorder. Two polymorphisms have been described at this locus (the Bal I and the Msp I Restriction Fragment Length Polymorphisms) that are useful in genetic studies. We therefore researched these polymorphisms in 60 patients suffering from bipolar affective disorder who were compared with 60 healthy volunteers. No statistical difference was observed between the whole patient sample versus the controls. However, one subgroup [homozygous for the (2-2) Bal I polymorphism] exhibits a characteristic clinical pattern consisting of: manic monopolar form of bipolar disorder, low age of onset and initiation by an acute delusional episode. A gender distribution difference for the Bal I polymorphism (chi 2 = 6.61, degrees of freedom = 1, P = 0.01) was then noted, the bipolar females being preferentially heterozygous, and the males homozygous. These results could involve the dopamine D3 receptor locus as a minor effect gene in the manic depression condition.