Cognitive Manic Symptoms Associated with the P2RX7 Gene in Bipolar Disorder

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.