Mental Health

Depression and Bipolar Disorder Gene Not Linked to Serotonin

Many antidepressants work by changing serotonin levels in the brain, which is why these classes of antidepressants are called Selective Serotonin Receptor Inhibitors (SSRIs). In May 2006, a study was published in the American Journal of Medical Genetics that suggests that a gene for major depressive disorders (including bipolar disorder) was found, and is not linked to serotonin. ScientistLive.com published a commentary about this study.

This gene is called P2RX7 and is found in humans and animals. This marked an advance in understanding the genetic basis of depressive disorders. Professor Barden was a lead investigator in the study and was quoted to say, “What is particularly exciting is that P2RX7 has nothing to do with serotonin.” Barden speculated that future antidepressants may directly target the P2RX7 gene, and current antidepressants may take weeks to have an effect because current antidepressants bypass P2RX7. In animal studies. directly targeting P2RX7 was shown to have an antidepressive effect.

Barden concluded that how P2RX7 works is still unknown, and may be part of a larger genetic network that is responsible for depression.

I’m including the Original Abstract for those of you curious about the scientific jargon:

Barden N, Harvey M, Gagné B, Shink E, Tremblay M, Raymond C, Labbé M, Villeneuve A, Rochette D, Bordeleau L, Stadler H, Holsboer F, Müller-Myhsok B. 2006. “Analysis of Single Nucleotide Polymorphisms in Genes in the Chromosome 12Q24.31 Region Points to P2RX7 as a Susceptibility Gene to Bipolar Affective Disorder.” Am J Med Genet Part B 141B:374-382.

Abstract
Previous results from our genetic analyses using pedigrees from a French Canadian population suggested that the interval delimited by markers on chromosome 12, D12S86 and D12S378, was the most probable genomic region to contain a susceptibility gene for affective disorders. Association studies with microsatellite markers using a case/control sample from the same population (n = 427) revealed significant allelic associations between the bipolar phenotype and marker NBG6. Since this marker is located in intron 9 of the P2RX7 gene, we analyzed the surrounding genomic region for the presence of polymorphisms in regulatory, coding and intron/exon junction sequences. Twenty four (24) SNPs were genotyped in a case/control sample and 12 SNPs in all pedigrees used for linkage analysis. Allelic, genotypic or family-based association studies suggest the presence of two susceptibility loci, the P2RX7 and CaMKK2 genes. The strongest association was observed in bipolar families at the non-synonymous SNP P2RX7-E13A (rs2230912, P-value = 0.000708), which results from an over-transmission of the mutant G-allele to affected offspring. This Gln460Arg polymorphism occurs at an amino acid that is conserved between humans and rodents and is located in the C-terminal domain of the P2X7 receptor, known to be essential for normal P2RX7 function. © 2006 Wiley-Liss, Inc.

© 2008 by Jane Chin, Ph.D. (email) All Rights Reserved.
Abstract logo images by Asif Akbar