Major depressive disorder (MDD) is a leading global health concern. Personalized medicine could enable a better response to antidepressants. Findings suggested optimal response genotypes of Val66Met g Show more
Major depressive disorder (MDD) is a leading global health concern. Personalized medicine could enable a better response to antidepressants. Findings suggested optimal response genotypes of Val66Met genetic polymorphism of brain-derived neurotrophic factor (BDNF) (rs6265) in Caucasian depressed patients: selective serotonin reuptake inhibitors (SSRIs) associated with better clinical improvement in Val/Val homozygotes and selective norepinephrine reuptake inhibitors (SNRIs) or tricyclic antidepressants (TCAs) with better clinical improvement in Met-allele carriers. We aim to replicate these findings with a meta-analysis. A systematic search of PubMed was performed. All included studies assessed the efficacy of one antidepressant class (SSRIs, SNRIs, or TCAs) in Caucasian patients with a major depressive episode (MDE) in the context of MDD according to BDNF Val66Met genotypes. The primary outcome was remission (MADRS ≤ 12 or HAMD ≤ 7); secondary outcomes were changes from baseline HAMD or MADRS scores and response (≥ 50% reduction). Seven studies were included. In total, 599 patients (357 Val/Val homozygotes and 242 Met-allele carriers) were analyzed. No significant association between optimal response genotypes and remission (190 (56.4%) in the optimal and 146 (54.3%) in the non-optimal genotype response group; fixed effects model: RR = 1.02, 95% CI [0.89; 1.18], p = 0.78) was observed. Similar results were observed for score changes and response. Sensitivity analyses confirmed these findings. Statistical power for primary outcome was 95%. We showed no significant association between the expected optimal response genotype of the BDNF Val66Met polymorphism and clinical improvement after antidepressant treatment in Caucasian depressed patients. Show less
Brain-derived neurotrophic factor (BDNF) plays an important role in the survival of dopaminergic neurons. Clinical studies have suggested that serum BDNF levels are reduced in patients with Parkinson' Show more
Brain-derived neurotrophic factor (BDNF) plays an important role in the survival of dopaminergic neurons. Clinical studies have suggested that serum BDNF levels are reduced in patients with Parkinson's disease (PD). However, no study has investigated peripheral BDNF levels and BDNF Val66Met polymorphism in the prodromal stage of PD and their relationship with disease conversion. In total, 120 patients with video-polysomnography confirmed isolated REM sleep behavior disorder (iRBD) and 120 healthy controls (HCs) were enrolled. Genetic analyses were performed, and plasma levels of BDNF were measured. All patients with iRBD underwent comprehensive clinical testing, and 107 iRBD patients were prospectively followed up. Plasma BDNF levels were significantly lower in the iRBD group than in HCs (18,878.85 pg/mL vs. 24,649.85 pg/mL, p = 0.002), but no differences were observed in BDNF Val66Met carrier rates between the two groups. Plasma BDNF levels did not differ significantly between BDNF Val66Met carriers and noncarriers. Notably, higher plasma BDNF levels were associated with an increased risk of short-term disease conversion (hazard ratio = 3.418, 95% CI: 1.520-7.684, p = 0.003), whereas BDNF Val66Met carrier rates showed no such association. Our findings suggest that plasma BDNF is significantly associated with iRBD and may likely serve as a prognostic biomarker for the development of neurodegenerative disease. However, the BDNF Val66Met polymorphism may not be involved in the pathogenesis of iRBD as well as phenoconversion in the studied population. Show less