Recent research suggests that the brain-derived neurotrophic factor (BDNF) may play a role in extinction learning. The goal of this study was to test whether variation in the BDNF Val66Met polymorphism is related to treatment response to exposure-based cognitive-behavior therapy (CBT), a form of extinction learning, in obsessive-compulsive disorder (OCD).

One hundred and six OCD patients from a specialized clinic, who underwent a standardized CBT treatment after partial or non-response to a 12-week pharmacological trial, were genotyped for the BDNF Val66Met and the relationship between genotype and treatment response was analyzed.

Among 98 CBT completers, 36% of those carrying the BDNF Met allele were rated as CBT responders compared to 60% of nonMet allele carriers (P = 0.027). When analyzing the different obsessive-compulsive symptom dimensions, in patients with contamination/cleaning symptoms, the Met allele was associated with a significantly worse CBT response (P<0.0001) and a lower obsessions severity decrease from pre- to posttreatment (P = 0.046).

Genetic variation in BDNF may be associated with treatment response in exposure-based CBT in OCD, especially in those patients exhibiting contamination/cleaning symptoms.

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.

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.

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).

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.