No association between the brain-derived neurotrophic factor gene and panic disorder in Japanese population

Abstract

Panic disorder (PD) is a severe and chronic psychiatric disorder, with significant genetic components in the etiology. Brain-derived neurotrophic factor (BDNF) gene, which has regulatory effects on neurotransmitter systems such as serotonin and dopamine, is a candidate for susceptibility locus of PD. This study investigated three single-nucleotide polymorphisms (SNPs) of BDNF (rs6265 (Val66Met), rs11030104 and rs7103411) in Japanese patients with PD and controls. No significant association was observed between the three SNPs and PD. No association of the Val66Met was consistent with two small studies in Japanese and Chinese populations. We therefore conclude that the BDNF polymorphism may not play a major role in PD in the East Asian populations. Keywords: brain-derived neurotrophic factor; genetic association; Japanese population; panic disorder; Val66Met polymorphism INTRODUCTION Panic disorder (PD) is an anxiety disorder characterized by panic attacks and anticipatory anxiety, with a lifetime prevalence of 1-3% and a female/male ratio of 2:1. 1 PD frequently takes a chronic course, with many remissions and relapses, occasionally complicated by comorbidity with other psychiatric disorders, such as agoraphobia and major depression. 2 It is generally accepted that PD has genetic as well as environmental causes. A 2.6-to 20-fold relative risk in the firstdegree relatives of proband with PD compared with the general population suggests a familial component in this disorder. 3,4 Twin studies show that about 40% of the liability toward PD consists of heritable factors. 5-7 Thus far however, the etiology of PD is currently unknown.Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, promotes the survival, differentiation and maintenance of a broad variety of central nervous system neurons. 8,9 BDNF has regulatory effects on multiple neurotransmitter systems, including serotonin 10 and dopamine, 11 and maybe involved in the etiology of stress-related disorders, such as depression and PTSD. Chronic administration of antidepressants, including selective serotonin reuptake inhibitors, increases BDNF expression in the hippocampus. 12 On the other hand, animal studies support the fact that environmental stressors, such as immobilization, decreased central

Is the Val66Met polymorphism of the brain‐derived neurotrophic factor gene associated with panic disorder? A meta‐analysis

“…Database search identified six studies that met the inclusion criteria (Lam et al ., ; Shimizu et al ., ; Lim et al ., ; Ishii et al ., ; Otowa et al ., ; Han et al ., ). In summary, a total of 20 potentially relevant articles were found after searching the PubMed and Embase databases.…”

“…() reported a significant association between Met/Met polymorphism and PD risk. Other previous case–control studies, however, reported no association between PD risk and the Val66Met polymorphism (Lam et al ., ; Shimizu et al ., ; Lim et al ., ; Otowa et al ., ; Konishi et al ., ; Konishi et al ., ; Han et al ., ). This meta‐analysis included 1,230 patients and 1,612 control subjects.…”

The BDNF gene Val66Met polymorphism as a modifier of psychiatric disorder susceptibility: progress and controversy

“…Further, given several association studies (n = 103-1241), there is also insufficient evidence to suggest that panic disorder, an anxiety disorder characterized by disabling and recurrent panic attacks, is associated with the Val66Met polymorphism. [81][82][83][84] Meta-analyses have also generally failed to report significant associations between Val66Met genotype or allelotype and anxiety disorders. 71 Ultimately, it may be the case that the Val66Met polymorphism only provides susceptibility to trait anxiety that is independent of a psychiatric diagnosis, with the aforementioned anxiety disorders presumably maintaining otherwise distinct etiologies.…”

Effect of variation in BDNF Val66Met polymorphism, smoking, and nicotine dependence on symptom severity of depressive and anxiety disorders

“…No association of BDNF Val 66 Met polymorphism has been found with anxiety disorders including generalized anxiety disorder (Surtees et al, 2007), panic disorder (Lam et al, 2004;Otowa et al, 2009;Shimizu et al, 2005) and post-traumatic stress disorder except in one community sample of children and adolescents (Tocchetto et al, 2011).…”