Bipolar Disorder

Bipolar disorder, previously known as manic-depressive psychosis, is a medical condition affecting the brain that manifests in the form of extreme shifts in a person’s mood, energy, and ability to function. The symptoms of bipolar disorder are much more severe than the normal fluctuations in mood that most people experience.

Our Research

We were the first to discover an association between human gene NR2E1 and bipolar disorder. The NR2E1 gene resides within a chromosomal locus for bipolar disorder and schizophrenia. Mice lacking the NR2E1 (Nuclear Receptor 2E1) gene display extremely violent behaviour. Male mice without this gene often injure—and sometimes even kill—siblings or intended mates. Female mice without this gene also show increased aggression and 50% of dams abandon their pups shortly after birth.

Recently, we demonstrated that the pathological aggression in these "fierce" mice can be corrected by the human NR2E1 gene. "Fierce" mice lacking the mouse NR2E1 gene, but carrying a copy of the human gene, showed normal brain development and behaviour. This work demonstrates the functional equivalency of the human and mouse genes when tested in mouse, and establishes a system to functionally evaluate the role of human genes in psychiatric disease.

Following these observations, we performed genetic association analyses in 394 patients with bipolar disorder, 396 with schizophrenia, and 479 controls using six common markers and haplotypes. We also performed a mutation screen of NR2E1 by resequencing 126 humans with bipolar disorder, schizophrenia, or aggressive disorders. We found that NR2E1 was associated with bipolar disorder I and II with an odds ratio of 0.77 (P = 0.013), which remained significant after correcting for multiple comparisons.

Publications

Kumar RA, McGhee KA, Leach S, Bonaguro R, Maclean A, Aguirre-Hernandez R, Abrahams BS, Coccaro EF, Hodgins S, Turecki G, Condon A, Muir WJ, Brooks-Wilson AR, Blackwood DH, Simpson EM. Initial association of NR2E1 with bipolar disorder and identification of candidate mutations in bipolar disorder, schizophrenia, and aggression through resequencing. Am. J. Med. Genet. B Neuropsychiatr. Genet. 147B(6):880-9. (2008) PMID 18205168