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21-03-2011 | Mental health | Article

Variant dopamine gene impacts mania risk in bipolar disorder


Free abstract

MedWire News: The risk for developing manic episodes in bipolar disorder appears to be influenced by genetic variation in a dopamine metabolizing enzyme, study results show.

The variant had no effect on the occurrence of depressive episodes, however, suggesting the existence of a heritable mechanism specifically for mania.

The occurrence of manic episodes is the distinguishing feature of bipolar disorder relative to other affective disorders. The dopaminergic system seems to play a central role in these manic episodes, which are considered to be hyperdopaminergic states.

It has been hypothesized that genetic factors affecting dopamine neurotransmission could influence individual susceptibility to mania.

Specifically, there has been recent interest in catechol-O-methyltransferase (COMT) - an enzyme that inactivates catecholamines (including dopamine).

The rs4680 polymorphism of COMT results in a valine to methionine amino acid substitution at position 158 of the membrane bound protein (or 108 in the soluble form), which reduces the activity of the enzyme.

In the current study, Francesco Benedetti (San Raffaele Scientific Institute, Milan Italy) and co-workers genotyped 163 patients with bipolar I disorder and assessed personal history of recurrence of the illness, taking into account available charts, case notes, and information provided by at least one relative.

Recurrence rates of manic and depressive episodes were evaluated by considering the occurring episodes of illness over the years from the onset of illness to the interview (recurrence rate=number of episodes/years duration of illness).

The distribution of COMT genotypes in the patients with bipolar I disorder did not significantly differ from that of the general population in Europe - Val/Val, n=45 (27%); Val/Met, n=87 (53%); Met/Met, n=31 (19%).

Benedetti et al report that the rs4680 genotype significantly influenced the recurrence of mania, with Met/Met homozygotes showing a significantly lower frequency of manic episodes than both Val/Val homozygotes and heterozygotes (0.0446 vs 0.0709 and 0.0739, respectively).

Analysis showed that carrying at least one copy of the Val allele was associated with an increased risk for mania. No significant effects of age, gender, and current ongoing lithium treatment were observed

"From a clinical point of view, the present findings suggest the possible usefulness of rs4680 in the management of bipolar disorder as a marker of the individual susceptibility to mania," the researchers comment in the Journal of Affective Disorders.

MedWire ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Andrew Czyzewski

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