Brain Derived Neurotrophic Factor (BDNF) gene variants association with age at onset and therapeutic response in schizophrenia

Abstract

Schizophrenia is a heterogeneous disease involving genetic and environmental factors. The frequency of structural brain abnormalities or physical anomalies supports a neurodevelopmental etiology, especially in early onset schizophrenia. Brain-Derived-Neurotrophic-Factor (BDNF) is involved in the neurodevelopment of dopaminergic (DA)-related systems and interacts with the meso-limbic DA systems, involved in the therapeutic response to antipsychotic drugs and substance abuse. In addition, BDNF promotes and maintains dopamine D3 receptor (DRD3) expression. In a French Caucasian population, we found no statistical difference in allele or genotype distribution of the BDNF gene dinucleotide repeat polymorphism (166-174 bp) between the whole group of schizophrenic patients and controls. By contrast, an excess of the 172-176 bp alleles was found in patients with late onset, in neuroleptic-responding patients and in non-substance-abusing patients. BDNF gene variants thus appear to be associated with developmental features of schizophrenia. In addition, this association with good treatment responding was independent from the association found with the DRD3 Ball gene polymorphism in the same population. These results suggest an independent contribution of each gene to a treatment-sensitive form of schizophrenia.

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

“…Although population studies have yielded divergent data about the association of variants in the BDNF gene with increased risk and developmental features of schizophrenia, [72][73][74][75][76][77][78] human postmortem studies suggest that individuals with schizophrenia have reduced expression of TrkB and BDNF in the cerebral cortex, 12,[79][80][81][82] as well as decreased BDNF protein levels in the serum. 83 In addition, various animal models of schizophrenia consistently show a downregulation of BDNF transcript or protein.…”

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

“…BDNF variants have been related to schizophrenia, but only marginal association or negative significance has been described in relation to treatment response. [141][142][143] NOTCH4, a developmental gene also involved in the regulation of neuron generation from stem cells, was not found individually associated with response but was suggested to interact with COMT to influence clinical outcome, 145 although the validity and biological significance of this finding requires investigation. The tumour necrosis factor-a (TNF-a) is a cytokine that mediates host response during inflammation and infection, and has been suggested to play a role in neurodevelopment and degeneration.…”

Association study between brain‐derived neurotrophic factor gene polymorphisms and methamphetamine abusers in Japan

“…BDNF interacts with TrkB receptor tyrosine kinase, playing several important roles such as; promotion of survival, differentiation and maintenance of neurons in peripheral nervous system and central nervous system; influences to axonal growth and connectivity; participation in the local responses to various types of neuronal stress or insults (Manji et al, 2003;Mattson et al, 2003). Furthermore, it also has been reported that the gene encoding BDNF might be an important candidate for susceptibility of neuropsychiatric disorders including bipolar disorder (Neves-Pereira et al, 2002;Sklar et al, 2002;Hashimoto et al, 2004), schizophrenia (Krebs et al, 2000), Parkinson's disease (Momose et al, 2002), and Alzheimer's disease (Ventriglia et al, 2002). In the studies reporting possible association of BDNF and these disorders, two SNPs of BDNF gene has been reported.…”