Malfunctioning circadian clock genes may be responsible for bipolar disorder in children. Researchers writing in the open access journal BMC Psychiatry found four versions of the regulatory gene RORB that were associated with pediatric bipolar disorder.

Alexander Niculescu from Indiana University School of Medicine, Indianapolis, US, worked with a team of researchers at Harvard, UC San Diego, Massachusetts General Hospital and SUNY Upstate Medical University to study the RORA and RORB genes of 152 children with the condition and 140 control children. They found four alterations to the RORB gene that were positively associated with being bipolar. Niculescu said, “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”.

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.

Notes:

Evidence for Genetic Association of RORB with Bipolar Disorder
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 and Ming T Tsuang
BMC Psychiatry (in press)

http://www.biomedcentral.com/bmcpsychiatry/

Source: Graeme Baldwin

BioMed Central

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Both attention deficit hyperactivity disorder (ADHD) and pediatric bipolar disorder (PBD) patients exhibit prefrontal dysfunction, although it is more extensive in the former group, conclude US researchers.

Both PBD and ADHD patients commonly have deficits of impulsivity, inattention, and poor behavioral inhibition. While the neural basis for these deficits has been examined, it has not been sufficiently contrasted and compared with healthy controls.

To investigate further, Alessandra Passarotti and colleagues from the University of Illinois Medical Center at Chicago studied 15 PBD patients with type I mixed or manic disorder, 11 ADHD patients, and 15 mentally healthy controls, with average ages of 13.20, 13.09, and 14.13, respectively.

The team performed functional magnetic imaging on the participants during a response inhibition task that examined the ability to inhibit execution of a motor response to a target when a stop cue is presented shortly before the target.

There were no significant demographic differences among the three groups. Both the PBD and ADHD groups had significant lower accuracy on the response inhibition task than controls, at 80% and 81% versus 87%, with no significant difference between the patient groups.

Compared with healthy controls, the PBD group had less activation on the right medial frontal gyrus, left inferior/middle frontal gyrus, and in the right pregenual anterior cingulate cortex (ACC), as well as increased activation in the left superior temporal gyrus and inferior parietal lobule and right posterior cingulate cortex.

The ADHD group had, compared with controls, less activation in the right dorsolateral prefrontal cortex (DLPFC), bilateral superior frontal gyrus, bilateral ventrolateral prefrontal cortex (VLPC), and left superior temporal gyrus, along with greater activation in the bilateral caudate and left cerebellum.

Furthermore, ADHD patients had reduced activity in the bilateral inferior frontal gyrus/VLPFC, bilateral middle frontal gyrus/DLPFC, right superior frontal gyrus, right middle temporal cortex, and left posterior cingulate versus PBD patients, and reduced activity in the occipital cortex and left post-central gyrus, the team notes in the journal Psychiatry Research: Neuroimaging.

The team concludes: “While in ADHD response inhibition de?cits may be driven by a more extensive dysfunction of the prefrontal cortex and motor control systems, in PBD they may be driven by more localized dysfunction of regulatory VLPFC and ACC regions.”

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

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