HOMA-IR increase after antidepressant treatment in depressed patients with the Met allele of the Val66Met BDNF genetic polymorphism.
BACKGROUND
The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with response to antidepressant drugs in depressed patients and with metabolic side effects after antipsychotic treatment. This study aims to assess the association between this polymorphism and insulin resistance after antidepressant treatment in depressed patients.


METHODS
One hundred forty-eight Caucasian patients with a current unipolar major depressive episode (DSM IV-TR) were genotyped for the BDNF Val66Met polymorphism and assessed at baseline and after 3 and 6 months of antidepressant treatment for the 'Homoeostasis model assessment of insulin resistance' (HOMA-IR) index, a valid measure of insulin resistance based on fasting plasma insulinaemia and glycaemia. Because validity assumptions were fulfilled, data were analysed using analysis of variance for repeated measures.


RESULTS
The 52 (35%) Met carriers and 96 (65%) Val/Val patients were not different at baseline for clinical characteristics and HOMA-IR. A significant Val66Met × time interaction (p = 0.02), a significant time effect (p = 0.03) and a significant Val66Met effect (p = 0.0497) were shown for HOMA-IR. A significant Val66Met × time interaction (p = 0.01) and a significant time effect (p = 0.003) were shown for fasting glycaemia. HOMA-IR and fasting glycaemia changes after antidepressant treatment were significantly higher in Met carrier than in Val/Val patients (HOMA-IR changes: Met: 0.71 ± 3.29 v. Val/Val: -0.16 ± 1.34, t = 2.3, df = 146, p = 0.02, glycaemia changes: Met: 0.09 ± 0.30 v. Val/Val: 0.02 ± 0.16, t = -2.0, df = 146, p = 0.045).


CONCLUSIONS
The Met allele of the Val66Met BDNF polymorphism confers to depressed patients a higher risk of insulin-resistance after antidepressant treatment. These patients could benefit from specific monitoring of metabolism and preventive measures.
['Martin|Séverine|S|', 'Colle|Romain|R|', 'El Asmar|Khalil|K|', 'Rigal|Adrien|A|', 'Vievard|Albane|A|', 'Feve|Bruno|B|', 'Becquemont|Laurent|L|', 'Verstuyft|Céline|C|', 'Corruble|Emmanuelle|E|']
D000328:Adult D000483:Alleles D000928:Antidepressive Agents D019208:Brain-Derived Neurotrophic Factor D003865:Depressive Disorder, Major D005260:Female D005602:France D005838:Genotype D006579:Heterozygote D006706:Homeostasis D006720:Homozygote D006801:Humans D007333:Insulin Resistance D008297:Male D008875:Middle Aged D020641:Polymorphism, Single Nucleotide D012074:Remission Induction D044465:Whites
Antidepressant Val66Met brain-derived neurotrophic factor insulin resistance major depressive episode major depressive disorder rs6265