title: 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.
authors: King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK. kathryn.lester@kcl.ac.uk
authors: K J
authors: KJ
authors: Lester
authors: J L
authors: JL
authors: Hudson
authors: M
authors: M
authors: Tropeano
authors: C
authors: C
authors: Creswell
authors: D A
authors: DA
authors: Collier
authors: A
authors: A
authors: Farmer
authors: H J
authors: HJ
authors: Lyneham
authors: R M
authors: RM
authors: Rapee
authors: T C
authors: TC
authors: Eley
mesh_terms: D000293:Adolescent; D000483:Alleles; D001008:Anxiety Disorders / Q000235:genetics* / Q000628:therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D015928:Cognitive Behavioral Therapy; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression / Q000235:genetics; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D020932:Nerve Growth Factor / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D020932:Nerve Growth Factor