Neurotrophic gene polymorphisms and response to psychological therapy

Abstract

Therapygenetics, the study of genetic determinants of response to psychological therapies, is in its infancy. Here, we investigate whether single-nucleotide polymorphisms in nerve growth factor (NGF) (rs6330) and brain-derived neutrotrophic factor (BDNF) (rs6265) genes predict the response to cognitive behaviour therapy (CBT). Neurotrophic genes represent plausible candidate genes: they are implicated in synaptic plasticity, response to stress, and are widely expressed in brain areas involved in mood and cognition. Allelic variation at both loci has shown associations with anxiety-related phenotypes. A sample of 374 anxiety-disordered children with white European ancestry was recruited from clinics in Reading, UK, and in Sydney, Australia. Participants received manualised CBT treatment and DNA was collected from buccal cells using cheek swabs. Treatment response was assessed at post-treatment and follow-up time points. We report first evidence that children with one or more copies of the T allele of NGF rs6330 were significantly more likely to be free of their primary anxiety diagnosis at follow-up (OR=0.60 (0.42–0.85), P=0.005). These effects remained even when other clinically relevant covariates were accounted for (OR=0.62 (0.41–0.92), P=0.019). No significant associations were observed between BDNF rs6265 and response to psychological therapy. These findings demonstrate that knowledge of genetic markers has the potential to inform clinical treatment decisions for psychotherapeutic interventions.

Hpa Axis Related Genes and Response to Psychological Therapies: Genetics and Epigenetics

“…In this study, we find genotype‐dependent changes in methylation during treatment are associated with treatment outcomes at follow‐up . Previous studies investigating both genetic26, 30, 32 and epigenetic26, 27 markers of response to psychological therapy have also demonstrated the largest effects at follow‐up. Future research of predictors and markers of response to psychological therapies would be improved by including this time point.…”

Genetics in child and adolescent psychiatry: methodological advances and conceptual issues

“…In a recent study, anxiety disordered children carrying two copies of the "s" allele of the serotonin transporter promoter polymorphism (5HTTLPR) were 20 % more likely to be disorder free at follow-up after CBT than l/l or s/l carriers [39]. The same group found a polymorphism in the gene for nerve growth factor (NGF) to be relevant for psychotherapy treatment outcomes in children suffering from anxiety disorder [74]. However, these findings await replication.…”

Nerve Growth Factor(s) Mediated Hypothalamic Pituitary Adrenal Axis Dysregulation Model in Stress Induced Genesis of Psychiatric Disorders

“…A study on male hamsters has shown that differential action of BDNF caused dominant- Single nucleotide polymorphic variants of BDNF (rs6265, Val66Met) and NGF (rs6330, Ala35Val) have been reported to be associated with anxiety phenotypes in humans (58).…”