Association study of BDNF Val66Met gene polymorphism with bipolar disorder and lithium treatment response in Indian population

Abstract

Background: The association of the Val66Met (rs6265) polymorphism in the brain-derived neurotrophic factor ( BDNF) gene with bipolar disorder (BD) and response to lithium treatment has been suggested, though inconsistently. The considerable diversity of allele frequency across different populations contributes to this. There is no data from South Asia till date. Hence, we examined the association of this polymorphism in BD cases from India, and its association with lithium treatment response. Methods: BD patients ( N = 301) were recruited from the clinical services of National Institute of Mental Health and Neurosciences (NIMHANS), India. Lithium treatment response for 190 BD subjects was assessed using Alda scale by NIMH life charts. Patients with total score ⩾7 were defined as lithium responders ( N = 115) and patients with score <7 were defined as lithium non-responders ( N = 75). Healthy controls ( N = 484) with no lifetime history of neuropsychiatric illness or a family history of mental illness were recruited as control set. Genotyping was performed by TaqMan genotyping assay. Results: Genotype and allele frequency of BDNF Val66Met SNP was significantly different (χ2 = 7.78, p = 0.02) in cases compared to controls, and the Val(G) allele was more frequent (χ2 = 7.08, p = 0.008) in BD patients. However, no significant difference is noted in genotype or allele frequencies of this polymorphism between the lithium responders and non-responders. Conclusions: The Val(G) allele of BDNF Val66Met polymorphism is associated with risk of BD in this sample, but it is not related to response to lithium.

Associations of BDNF/BDNF-AS SNPs with Depression, Schizophrenia, and Bipolar Disorder

“…A study by Paul et al (2021) revealed significant differences in the rs6265 polymorphism, notably observing a higher occurrence of the G (Val) allele among BD patients from India [ 116 ]. Additionally, in a recent study by Yoldi-Negrete et al (2022), it was concluded that being an rs6265 Met carrier is a significant predictor of impaired functioning in individuals with BD-I [ 117 ].…”

“…However, in their meta-analysis, Ehret et al (2013) concluded that the Val66Met polymorphism cannot predict lithium treatment response in BD patients [ 143 ]. Similarly, Paul et al (2021) did not find a significant association between the rs6265 polymorphism and the response to lithium treatment in BD patients from India [ 116 ]. Interestingly, Lee et al (2014) found a significant association between the addition of memantine to valproic acid in Val66Met heterozygote carriers treated for BD-II, resulting in a decrease in depressive symptoms compared to the use of valproic acid with a placebo [ 144 ].…”

Association of BDNF risk variant and dorsolateral cortical thickness with long‐term treatment response to valproate in type I bipolar disorder: An exploratory study

“…Other studies have linked BDNF rs1519480 with BD (Liu et al, 2008), particularly the allele C of this SNP reported an association with type I bipolar disorder (Sears et al, 2011). BDNF has also been involved in treatment response to antidepressants (Cardoner et al, 2013) and mood stabilizers (Paul et al, 2021), which might be explained by the effects of this neurotrophic agent on brain structure (Post, 2007). BDNF rs7124442 was associated in previous research with treatment response to antidepressants (Domschke et al, 2010).…”

Repurposing psychopharmacology: A two-way street?

“…Faßbender et al (2021) report a study which examined GABAergic modulation of performance in response inhibition and interference control tasks and found evidence for GABAergic involvement in performance on both types of tasks. Paul et al (2021) examined the association of the BDNF Val66Met gene polymorphism with bipolar disorder and lithium treatment response in an Indian population. Biomarkers of lithium response would be a great clinical utility; however, the authors report that although the Val(G) allele of BDNF Val66Met polymorphism is associated with risk of BD in their sample, this was not related to response to lithium.…”