Journal club online: Therapygenetics, a study of neurotrophic polymorphisms and response to psychological therapy

A paper just out in Translational Psychiatry by Lester and collegues exemplifies the ideas of the novel field of therapygenetics – how individual genetic variation impacts psychological treatment response.

In this study, 374 anxiety-disordered children who had completed a standardized cognitive behaviour therapy, were genotyped for single nucleotide polymorphisms (SNPs) in the nerve growth factor (NGF) (rs6330), brain-derived neurotrophic factory (BDNF) (rs6265) and in the serotonin transporter (5-HTTLPR) gene. These genes are considered important in synaptic plasticity and response to stress, and are expressed in areas in the brain responsible for fear and mood regulation.

Primary outcome measure was simply whether or not the participant fulfilled the anxiety diagnosis criteria post treatment. Treatment response was assessed immediately after treatment and at follow-ups. Lester and colleagues found that participants with one or more copies of the t-allele of NGF rs6330 were significantly more likely to be free of their diagnosis at follow-up. No interactional effect was observed between BDNF rs6265 or the 5-HTTLPR and treatment response. However, the 5-HTLLPR had a significant main effect as a predictor for treatment prognosis.

The authors reason that tyhe findings on NGF could be beneficial in helping to decide whether a child is likely to benefit from standard CBT or if further interventions should be considered.

Lester KJ, Hudson JL, Tropeano M, Creswell C, Collier DA, Farmer A, Lyneham HJ, Rapee RM, Eley TC. Neurotrophic gene polymorphisms and response to psychological therapy. Transl Psychiatry. 2012 May 1;2:e108.


 For more on this topic, read:

Journal Club online: What Dobermans can teach us on OCD genetics

Dogs sometimes suffer from behaviors such as tail chasing, flank or blanket sucking and other repetetive behaviors that can be harmful and that are diagnosed as Canine Compulsive Disorder and considered an analog to OCD in humans. The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. These wanted traits may also lead to an accumulation of a disorder within one breed and may be of special interest when studying the genetics of certain traits.

Dodman and collegues studied 92 doberman pinchers (pet dogs) that had flank or blanket sucking and controls with a genome wide association study (GWAS) and found a new canidate gene; CDH2. CDH2 is widely expressed,
mediating synaptic activity-regulated neuronal adhesion. Dogs showing multiple compulsive behaviors had a higher frequency of the risk allele than dogs with a less severe phenotype. Kerstin Lindblad-Toh and others at Broad Institute and Uppsala University are continuing to investigate this and other candidate genes. A recent Finnish study by Tiira et al of tail chasers but in 3 other dog breeds than Dobermans failed to find an association with CDH2.

For those interested in a more detailed review of animal models in OCD we recommend a review by Albeleda and Joel in Neuroscience 2012 (see below for full reference).

Dodman NH, Karlsson EK, Moon-Fanelli A, Galdzicka M, Perloski M, Shuster L, Lindblad-Toh K, Ginns EI. A canine chromosome 7 locus confers compulsive disorder susceptibility. Mol Psychiatry. 2010 Jan;15(1):8-10.

Tiira K, Hakosalo O, Kareinen L, Thomas A, Hielm-Björkman A, et al. (2012) Environmental Effects on Compulsive Tail Chasing in Dogs. PLoS ONE 7(7):e41684. doi:10.1371/journal.pone.0041684

Albelda N, Joel D. Current animal models of obsessive compulsive disorder: an update. Neuroscience. 2012 Jun 1;211:83-106.