Genetic variability associated with increased suicide risks with bipolar disorder

PHILADELPHIA — Researchers have discovered connections between the IMPA2, INPP1 and GSK3B genes and the emergence of suicidal behavior in patients with bipolar disorder, according to international study results presented here at the 2012 American Psychiatric Association Annual Meeting.

Antoni Benabarre, MD, PhD, and colleagues from Spain and the United States originally set out to verify whether the molecular variation at the IMPA1, IMPA2, INPP1 and GSK3A and GSK3B genes could serve as potential markers for suicidal behavior in patients with bipolar disorder (BP). According to the researchers, patients with BP are among those at the highest risk for suicidal behavior, and although lithium is one of the most widely used and effective mood stabilizers for patients with BP, the reasons for its effectiveness are unclear.

The researchers recruited 199 patients (102 males and 97 females, unrelated) with BP type 1 or type 2 from the Bipolar Disorder Unit of the Hospital Clinic of Barcelona and mental health services in Oviedo, Spain. Patients were grouped and compared according to the presence or absence of suicidal behavior, which the researchers defined as the presence of at least one suicide attempt. Adhering to standard protocols, the researchers extracted genomic DNA from blood samples from each patient. “Several polymorphisms at the IMPA1, IMPA2, INPP1, GSK3A and GSK3B genes were genotyped,” they wrote.

Single-marker analysis revealed a number of connections between some of the variants at the IMPA2, INPP1 and GSK3B genes and suicidal behavior in patients with BP on genotypic and allelic levels, according to the researchers. They found no association between the IMPA1 and GSK3A gene polymorphisms and suicidal behavior.

Results also showed that patients carrying AA and GG genotypes of the rs669838-IMPA2 and the rs4853694-INPP1 genes presented higher risk for suicide. The researchers discovered an association between two single-nucleotide polymorphisms related to the GSK3B gene and the emergence of suicidal behavior. Those patients carrying the T allele of the rs1732170-GSK3B and A carriers of the rs11921360-GSK3B “presented higher risk of attempting suicide compared to those patients who carried CC genotypes, respectively.” Analysis showed significant differences in haplotype distributions regarding INPP1 and GSK3B genes, they wrote.

The researchers concluded that the data would ultimately strengthen previous study results demonstrating the significant role of genetic variability along the phosphoinositol and Wnt/beta-catenine signaling pathways in suicidal behavior and BP.

“We observed that a population of patients with bipolar disorder who exhibited greater suicidal behavior has changes in genetics,” Benabarre said. “In the future we might be able to identify which patients are at greater risk for suicide. Perhaps most interestingly, patients with bipolar disorder who commit suicide have polymorphic changes in the same way as the mechanism of action in lithium.”

For More Information:
Benabarre A. Symposium NR9-02. Presented at: the 2012 American Psychiatric Association Annual Meeting; May 5- 9, 2012; Philadelphia.

Disclosure: Dr. Benabarre reports no relevant financial disclosures.