Val66Met polymorphism and serum brain‐derived neurotrophic factor in bipolar disorder: an open‐label trial

Abstract

. Val66Met polymorphism and serum brainderived neurotrophic factor in bipolar disorder: an open-label trial.Objective: Brain-derived neurotrophic factor (BDNF) is consistently associated with acute mood episodes in bipolar disorder, but there is a lack of longitudinal data to support this hypothesis. In this 16-week open-label clinical trial, we tested the predictive role of BDNF Val66Met polymorphism on serum BDNF levels and the relationship of serum BDNF and clinical response in people with bipolar disorder during an acute illness episode. Method: Sixty-four people with bipolar disorder who were medicationfree at baseline and in an acute mood episode were recruited. They were matched with 64 healthy controls. Clinical evaluation, serum BDNF, and BDNF Val66Met polymorphism were determined at baseline, and change in serum BDNF was assessed in patients at weeks 2, 4, 8 and 16. Results: There were no differences between patients and controls in serum BDNF or in frequencies of the BDNF Val66Met polymorphism genotype at baseline. The multivariable model showed that Met carriers had a significantly different change in BDNF levels compared with Val homozygotes. Not achieving a complete remission was also associated with lower prospectively assessed BDNF levels. Conclusion: This study provides the first longitudinal evidence that both the BDNF Val66Met polymorphism and remission status predict change in circulating BDNF levels. Significant Outcomes• People with bipolar disorder had a differential change in peripheral levels of brain-derived neurotrophic factor along the treatment of mood episodes depending on their Val66Met genotype.• Met carriers of Val66Met genotype had a significantly different trajectory and a tendency for a less substantial increase in peripheral levels than Val homozygotes.• Change in brain-derived neurotrophic factor levels was associated with treatment response. Limitations• There were no differences in brain-derived neurotrophic factor levels between patients and controls at baseline; this is possibly due to a floor effect.• Owing to the naturalistic design of the study, we could not control for the effect of each particular treatment.

Peripheral blood brain-derived neurotrophic factor in bipolar disorder: a comprehensive systematic review and meta-analysis

“…BDNF genotype was investigated in three of the included studies, with two finding no association between the Val66Met BDNF gene single-nucleotide polymorphism and BDNF levels, 40,50 and one study finding lower BDNF levels in bipolar disorder patients carrying the Met allele compared with Val homozygotes. 46 A recent meta-analysis, however, did not find any association between the BDNF Val66Met polymorphism and bipolar disorder. 133 Childhood abuse and neglect have been associated with worsening of the clinical course of BD 134 in a possible dose-response relationship.…”

“…11,13,19,20,26,[38][39][40][41][42] Ten studies provided data for comparisons between affective states in bipolar disorder patients, 12,19,20,26,38,41,42,46,48,65 of which two studies 12,26 included within-subject comparisons between a manic and euthymic state and one study 26 included withinsubjects comparisons between a depressed and euthymic state and a depressed and manic state (Supplementary Table 2-4S). Seven studies investigated changes in BDNF levels before and after treatment of an acute affective episode, 12,21,43,46,47,57,64 with follow-up periods ranging from 4 to 52 weeks. In five studies the intervention included a combination or different medication types (lithium, antipsychotics and anticonvulsants), 12,46,47,57,64 one study investigated BDNF changes before and after lithium treatment 43 and one study investigated changes before and after valproate treatment 21 (Supplementary Table 5-6S).…”

“…Seven studies investigated changes in BDNF levels before and after treatment of an acute affective episode, 12,21,43,46,47,57,64 with follow-up periods ranging from 4 to 52 weeks. In five studies the intervention included a combination or different medication types (lithium, antipsychotics and anticonvulsants), 12,46,47,57,64 one study investigated BDNF changes before and after lithium treatment 43 and one study investigated changes before and after valproate treatment 21 (Supplementary Table 5-6S). Of the included studies, 33 were published as peer-reviewed articles, while two were available as conference abstracts only.…”

“…47 Clinical and demographical information on participants was limited. BMI was available in eight studies, 13,21,26,46,47,53,61,62 information on alcohol use available in four studies, 26,38,46,59 information on exercise available in one study 26 and information on smoking status in three studies; 26,38,59 no study matched groups by any of these variables. Duration of current affective state was not available in any study.…”

“…Blinding of laboratory staff to the clinical state of participants was reported in eight studies. 21,26,46,50,53,56,63,65 One study reported assigning samples randomly through enzyme-linked immunosorbent assay procedures. 26 Risk of bias and study quality within studies.…”