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

Schizophrenia is a heterogeneous disease involving genetic and environmental factors. The frequency of structural brain abnormalities(1,2) or physical anomalies(3) supports a neurodevelopmental etiology, especially in early onset schizophrenia.(4) Brain-Derived-Neurotrophic-Factor (BDNF) is involved in the neurodevelopment of dopaminergic (DA)-related systems(5,6) and interacts with the meso-limbic DA systems,(7-10) involved in the therapeutic response to antipsychotic drugs(11) and substance abuse.(12) In addition, BDNF promotes and maintains dopamine D3 receptor (DRD3) expression.(13) 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)(14) 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 Ban gene polymorphism in the same population.(15) These results suggest an independent contribution of each gene to a treatment-sensitive form of schizophrenia.