A team of researchers said this week that they may have identified the genes responsible for bipolar disorder in children. Their study, published in BMC Psychiatry, implicates malfunctioning circadian clock genes, four alterations of the RORB gene to be specific, in the development of the disorder.

Scientists studied the RORA and RORB genes of 152 children with Bipolar and 140 control children. They found four alterations to the RORB gene that were positively associated with being bipolar. "Our findings suggest that clock genes in general and RORB in particular may be important candidates for further investigation in the search for the molecular basis of bipolar disorder," explained co-author Alexander Niculescu.

RORB is mainly expressed in the eye, pineal gland and brain. Its expression is known to change as a function of circadian rhythm in some tissues, and mice without the gene exhibit circadian rhythm abnormalities.

According to Niculescu, "Bipolar disorder is often characterized by circadian rhythm abnormalities, and this is particularly true among pediatric bipolar patients. Decreased sleep has even been noted as one of the earliest symptoms discriminating children with bipolar disorder from those with attention deficit hyperactivity disorder (ADHD). It will be necessary to verify our association results in other independent samples, and to continue to study the relationship between RORB, other clock genes, and bipolar disorder".

Pediatric bipolar disorder is a controversial diagnosis characterized by alternating bouts of depression and mania in children, although it does not affect all young people in the same way and the duration and severity of the disorder can vary enormously.

Citation: Casey L McGrath, Stephen J Glatt, Pamela Sklar, Helen Le-Niculescu, Ronald Kuczenski, Alysa E Doyle, Joseph Biederman, Eric Mick, Stephen V Faraone, Alexander B Niculescu, Ming T Tsuang, 'Evidence for Genetic Association of RORB with Bipolar Disorder',
BMC Psychiatry 2009, doi:10.1186/1471-244X-9-70