Cognitive manic symptoms associated with the P2RX7 gene in bipolar disorder

Authors


  • LB has received consultancy fees from Bristol-Myers Squibb; and has been reimbursed by Eli Lilly & Co. and Bristol-Myers Squibb for conference presentations. ML has received research grants from AstraZeneca; has received reimbursement for lecture presentations from Eli Lilly & Co., AstraZeneca, and Wyeth; and has served on advisory boards for AstraZeneca and Lundbeck. GE has been a consultant for AstraZeneca and Janssen-Cilag; and his wife is a shareholder of AstraZeneca. UÖ has received grant/research support from Bristol-Myers Squibb and Janssen-Cilag; and has been a consultant for or received speaker fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., and Pfizer. PN, DSH, IRE, LT-B, MS, and LF have no conflicts of interest to report.

Corresponding author:
Lena Backlund, M.D., Ph.D.
The Section for Affective Disorders
Karolinska University Hospital Huddinge, M56
S-141 86 Stockholm, Sweden
Fax: 46-8-58586630
E-mail: lena.backlund@sll.se

Abstract

Backlund L, Nikamo P, Sudic Hukic D, Römer EK I, Träskman-Bendz L, Landén M, Edman G, Schalling M, Frisén L, Ösby U. Cognitive manic symptoms associated with the P2RX7 gene in bipolar disorder. Bipolar Disord 2011: 13: 500–508. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S.

Objective:  Several genetic loci have been suggested to be associated with bipolar disorder but results have been inconsistent. Studying associations between bipolar symptoms and candidate genes may better expose this relationship. Here we investigate the association between bipolar key symptoms and the P2RX7 gene.

Methods:  Key symptoms of mania were rated in two sets of medicated bipolar disorder patients (n = 171 and n = 475) at two specialized outpatient clinics for affective disorders and three regular psychiatric outpatient units in Sweden. The relationships between all manic symptoms according to DSM-IV were entered in a principal component analysis. We used a case–case model to reduce the genetic heterogeneity and tested associations between four factors related to manic symptoms and their association to four single nucleotide polymorphisms in the P2RX7 gene.

Results:  The combination of the cognitive symptoms, distractibility, talkativeness, and thought disorder was significantly associated with rs1718119 in the P2RX7 gene in Set 1 [odds ratio (OR) = 1.78; p = 0.011]. The association was re-tested in the second set (OR = 1.42; p = 0.009). In the total sample, the association was even stronger (OR = 1.49; p < 0.001). None of the other factors was associated with the P2RX7 gene. Within the first factor, the distractibility symptom accounted for a significant portion of the association to rs1718119 (p = 0.016).

Conclusion:  There is an association between specific symptoms of bipolar disorder and the P2RX7 gene. This finding may open up new approaches to elucidating the neurobiology behind bipolar symptoms.

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