Investigation of the genetic interaction between BDNF and DRD3 genes in suicidal behaviour in psychiatric disorders

Abstract

Objectives. Suicide is a serious public health concern, and it is partly genetic. The brain-derived neurotrophic factor (BDNF) gene has been a strong candidate in genetic studies of suicide (Dwivedi et al., Arch Gen Psychiatry 2010;60:804–815; Zai et al., Prog Neuropsychopharmacol Biol Psychiatry 2012;34:1412–1418) and BDNF regulates the expression of the dopamine D₃ receptor. Objective. We examined the role of the BDNF and DRD3 genes in suicide. Methods. We analysed four tag single-nucleotide polymorphisms (SNPs) in BDNF and 15 SNPs in the D₃ receptor gene DRD3 for possible association with suicide attempt history in our Canadian sample of Schizophrenia (SCZ) patients of European ancestry (N = 188). Results. In this sample, we found a possible interaction between the BDNF Val66Met and DRD3 Ser9Gly SNPs in increasing the risk of suicide attempt(s) in our SCZ sample. Specifically, a larger proportion of SCZ patients who were carrying at least one copy of the minor allele at each of the Val66Met and Ser9Gly functional markers have attempted suicides compared to patients with other genotypes (Bonferroni P < 0.05). However, we could not replicate this finding in samples from other psychiatric populations. Conclusions. Taken together, the results from the present study suggest that an interaction between BDNF and DRD3 may not play a major role in the risk for suicide attempt, though further studies, especially in SCZ, are required.

Key words::

• suicide
• brain-derived neurotrophic factor
• genetics
• schizophrenia
• dopamine receptor DRD3

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Acknowledgements

This study was supported by Grant 2PDF-00065-1208-0609-1209 awarded to [CCZ] from the American Foundation for Suicide Prevention. The content is solely the responsibility of the authors and does not necessarily represent the official views of the American Foundation for Suicide Prevention. Other funding sources include: Canadian Institutes for Health Research [JLK, JBV, VdL], Eli Lilly [CCZ], Brain and Behavior Research Foundation (NARSAD) [AKT, CCZ], STAGE program [VG], CAMH Foundation [VG], the Research Council of Norway (#217776, #223273) [OAA], and KG Jebsen Foundation and South-East Norway Health Authority (#2013-123) [OAA]. The collection of the IOP and CA2 samples was supported by funding from GlaxoSmithKline and CA1 from Pfizer. Dr. Yilmaz is supported by the National Institutes of Health (NIH) Grant T32MH076694 (PI: Bulik).

Statement of Interest

JLK: honoraria from Roche, Novartis, and Lilly. CCZ: honorium from WebMD for Medscape review. JLK & CCZ: patent application “Genetic Markers Associated with Suicide Risk and Methods of Use Thereof” submitted. OAA: received speaker's honoraria from GSK, Lilly, Otsuka, and Lundbeck. MM, IES, ZY, VdL, AKT, AS, GCZ, SAS, JS, NK, BLF, ASK, PIF, AEV, SD, and JBV reported no conflict of interest.