Association Between BDNF Gene Variant Rs6265 and the Severity of Depression in Antidepressant Treatment-Free Depressed Patients

Abstract

Background: Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity, and its dysregulation has been associated with the pathogenesis of mood and anxiety disorders. Prolactin (PRL) is a pituitary hormone which is also produced as a cytokine by immune cells and could be a neurotrophic factor regulating the functional activity of stress-related mechanisms. Aim: To investigate the possible relationship between depressive state and BDNF and PRL genotypes or levels with special reference to severity of depression. Methods: Participants of 18-70 years with a clinical diagnosis of depressive disorder of at least moderate severity were included. These patients had not been treated with antidepressant drugs before admission to hospital during the preceding period of the last 6 months, and 54.5% had never been treated with antidepressant drugs during their entire life. The DNA was genotyped for rs1341239 within the prolactin and for rs6265, rs7124442, and rs11030104 within the BDNF gene. Rs11030104 violated the Hardy-Weinberg equilibrium distribution and was excluded from further analyses. BDNF and prolactin concentration was measured in serum by MAGPIX multiplex analyzer (Luminex, USA) using MILLIPLEX ® MAP kit (Merck, Germany). Genetic associations were determined by sequentially regressing prolactin, BDNF, 17-items Hamilton's Depression (HAMD-17) and Clinical Global Impression scale, Severity (CGI-S) ratings, and depression (absent/present) on the available SNPs. Genetic associations were evaluated assuming an additive model. Results: A total of 186 depressed patients (of which 169 were women) and 94 healthy controls (67 women) were genotyped. After excluding subjects without genetic information on

Evaluation of 5-HTTLPR (insertion/deletion) and BDNF (rs6265) genetic variations in the Slovakian individuals suffering from affective disorders

“…Conversely, a recently published case-control study has demonstrated positive relationships between T allele and the risk of major depression (Aldoghachi et al 2019). In the other study, T allele was associated only with the severity of depression (Losenkov et al 2020). Although an animal study identified a relationship between MetMet genotype and increased risk of anxietyrelated behavior, we found no impact of rs6265 on ANXD susceptibility.…”

Single nucleotide polymorphism of BDNF Val66Met (rs6265) and its association to neuropsychiatric disorders

“…Losenkov and colleagues found an association between BDNF rs6265 and the 17item Hamilton depression rating scale (p=0.014) but not between BDNF rs6265 and the BDNF level. In the same study, the BDNF level was not reported to be associated with depression, indicating that BDNF rs6265 may only be involved in the severity of the disorder (Losenkov et al, 2020). Similarly, no significant difference was observed in the BDNF levels of 61 medicated depression patients and 50 controls (p=0.81), even following a course of electroconvulsive therapy.…”

BDNF, A Focus to Major Depression

“…Also, the data has shown that there is a reduction of BDNF in the prefrontal cortex, amygdala and hippocampus of patients with this patology [7,73,74] as well as in postmortem brain of victims of suicide and depression [9]. In addition, it has been observed that stress, one of the main triggers of mood disorders such as anxiety and depression [75,76] induces a decrease in BDNF [10,77]. In line with these data, exposure to stress factors, which is one of the most used approaches to model depression in experimental animals, promoted a decrease in the levels of BDNF and TrkB expression in the hippocampus, cortex and amygdala of animal models of stress such as social defeat, containment stress (immobilization) and maternal deprivation [75,[78][79][80].…”