PCNT2 levels may play bipolar disorder role

28 March 2008

MedWire News: Increased expression of the pericentrin 2 (PCNT2) gene in the brain and peripheral blood may play a role in the pathophysiology of bipolar disorder, Japanese study findings indicate.

Previous research has revealed that the gene disrupted-in-schizophrenia 1 (DISC1) is a potential causative gene for psychoses. In addition, PCNT2 has been shown to interact with DISC1, and it is posited that the DISC1 signaling pathway may be involved in the pathology of major psychiatric disorders, rather than the DISC1 molecule itself.

Kazuhiko Nakamura, from Hamamatsu University School of Medicine, and colleagues therefore used TaqMan real-time quantitative reverse transcriptase polymerase chain reaction to measure PCNT2 mRNA levels in prefrontal cortex samples obtained at postmortem from 34 bipolar disorder patients, 31 schizophrenia patients, and 32 controls.

In addition, the team examined PCNT2 mRNA levels in peripheral blood lymphocytes from 21 bipolar disorder patients, 21 schizophrenia patients, 33 patients with depression, and 57 controls. Twenty three single nucleotide polymorphisms (SNPs) were also genotyped in 285 bipolar disorder patients and 287 age- and gender-matched controls.

The results, published in the journal Biological Psychiatry, demonstrate that PCNT2 expression in the brain was significantly higher in the bipolar disorder group than in controls and schizophrenia patients, at averages of 5.26 versus 2.22 and 2.91, respectively. There were no significant differences between schizophrenia patients and controls, between psychotic and non-psychotic individuals, and between medicated and non-medicated bipolar disorder patients.

In peripheral blood, bipolar disorder and depression groups had significantly higher PCNT2 expression than control individuals, at 1.14 and 1.22 versus 0.88, respectively. Expression in schizophrenia patients, at 0.93, was not significantly greater than that seen in controls. Bipolar disorder patients in remission also had significantly higher PCNT2 expression than controls, at 1.11.

None of the SNPs studied were significantly associated with bipolar disorder, although there was a weak tendency for association with two intronic SNPs.

"Our findings suggest that enhanced expression of PCNT2 might be implicated in the pathophysiology of bipolar disorder: the levels of PCNT2 mRNA in lymphocytes might be a useful biological marker of bipolar disorder," the team concludes.

Free abstract