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18-11-2009 | Mental health | Article

Circadian rhythm genes linked to pediatric bipolar disorder


Free abstract

MedWire News: Polymorphisms in two genes related to the circadian rhythm may be associated with the development of pediatric bipolar disorder, although not with age at onset, US researchers have discovered.

Building on observations that, particularly in children, bipolar disorder is characterized by rapid cycling and switching of mood episodes, there has been interest in the role of circadian genes in the development of the disorder.

As retinoic acid receptor (RAR)-related orphan receptor alpha (RORA) and beta (RORB) genes have been linked to bipolar disorder in a mouse model, Alexander Niculescu, from Indiana University in Indianapolis, and colleagues studied 153 probands with childhood-onset bipolar I disorder and two affected parents, 152 independent, non-overlapping cases, and 140 healthy controls.

The participants, who had average ages of 17.5 years, 20.3 years, and 42.9 years, respectively, were genotyped for 322 single nucleotide polymorphisms (SNPs) in the RORA gene and 44 SNPs in the RORB gene.

Eighteen RORA SNPs and eight RORB SNPs in the family sample, and 13 RORA SNPs and 16 RORB SNPs in the case sample were significantly associated with bipolar disorder on initial analysis. However, no RORA SNPs and only four RORB SNPs survived Bonferroni correction: rs1157358, rs7022435, rs3750420, and rs3903529.

Interestingly, all of these SNPs were significant only in the case versus control sample and had odds ratios in the opposite direction in the family sample, giving overall odds ratios for bipolar disorder of 1.162, 1.150, 1.176, and 1.094, respectively.

Three haplotype blocks on RORB, indicating a further 11 SNPs, were linked to bipolar disorder in the case sample but not the family sample. No RORA or RORB SNPs were associated with bipolar age at onset.

The team writes in the journal BMC Psychiatry: “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.

“These results are supported by our current understanding of the expression, localization, and possible role of RORB in the brain and are also consistent with data from animal models of bipolar disorder.”

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

By Liam Davenport

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