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

Free abstract

• New Light On Bipolar Treatment Drugs - Potential Mechanism Identified For Lithium Operation In The Brain
• Childhood ADHD impacts on clinical course of bipolar disorder
• Pitt Researchers To Study Effects Of Early Intervention For Children Of Parents With Bipolar Disorder

Individuals at high risk for hypomania have alterations in sleep and circadian activity similar to those seen in bipolar disorder patients, indicating that such phenomena are not simply an artefact of the illness, conclude UK researchers.

It is common for bipolar disorder patients to experience sleep and circadian rhythm disturbances, which are associated with illness severity and recurrence. However, the premorbid occurrence and significance of such disturbances is not known.

Steven Jones (Lancaster University) and Dave Ankers (South Staffordshire and Shropshire Healthcare NHS Foundation Trust) studied 31 individuals at behavioral risk for hypomania, as measured on the Hypomanic Personality Scale (HPS), and 24 age- and gender-matched healthy controls.

The participants wore an actigraph for 7 days to obtain sleep and circadian activity data, and completed the HPS, the Hypomanic Interpretations Questionnaire (HIQ), the Internal State Scale (ISS), and a sleep diary.

At-risk individuals scored significantly higher than controls on the HIQ, with the results indicating that not only did at-risk participants make more positive self-referent appraisals for hypomania-relevant experiences than controls, but alsohad more of those experiences.

The team also found that at-risk individuals had a significantly reduced relative amplitude of activity cycle than controls, at 0.81 versus 0.86, suggesting that there was a smaller difference between the most active and least active periods in a day.

Hypomania-risk participants had a significantly shorter sleep duration than controls, at 6:53 versus 7:28 h:m, as well as significantly more variable sleep duration, fragmentation of sleep, and sleep efficiency. They also reported significantly later bedtimes than controls, at 1:20 versus 0:16 h:m.

The team writes in the Journal of Clinical Psychology: “This study found some evidence that circadian markers do differ in those putatively at risk for bipolar disorder when compared with controls.

“This may indicate that circadian differences exist prior to illness onset and could, therefore, represent a core vulnerability for the disorder.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

Free abstract

• Stanford To Offer Bipolar Education Day On July 25
• Having Parents With Bipolar Disorder Associated With Increased Risk Of Psychiatric Disorders