In a collaboration between Karolinska Institutet and Uppsala University, we studied three genetic polymorphisms in the monoamine system (5-HTTLPR, COMT val158met, TPH2 G-703T) and outcome of cognitive behavioral therapy (CBT) in social anxiety disorder (SAD) in over 300 patients. This is one of the largest genetic studies ever made on adults with SAD and CBT outcome. Monoamine-related gene polymorphisms have previously been tied to amygdala reactivity, treatment efficacy and fear extinction processes and was hereby reasoned to influence the outcome of CBT. However, none of our polymorphisms were associated with CBT outcome at long term follow-up. In our subsamples we found contradictory significant effects immediately after treatment. Even though CBT is an effective treatment of anxiety disorders, many patients (25-50%) do not respond sufficiently. Therefore, there is a need to improve not only the treatments but also how patients are selected for treatment in order to optimize the efficacy. Therapygenetics attempts to explore the relationship between genetic variation and psychological treatment response. Ultimately, such knowledge could be used to tailor therapies based on patients’ biological markers, which in turn, could improve therapeutic outcome.
Rücklab’s Evelyn Andersson visited Department of Psychiatry at UCSD last week who hosts prominent researchers such as prof. Hagop Akiskal, famous for his extensive work on mood disorders and prof. John Kelsoe, a pioneer in investigating molecular genetics and bipolar disorder for over 20 years.
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:
- Beevers CG, McGeary JE. 2012. Therapygenetics: moving towards personalized psychotherapy treatment. Trends Cogn Sci 16:11-12.
- Bockting CL, RJ Mocking, A Lok, MW Koeter, AH Schene. 2012. Therapygenetics: the 5HTTLPR as a biomarker for response to psychological therapy? Mol Psychiatry.
- Eley, TC, JL Hudson, C Creswell, et al. 2012. Therapygenetics: the 5HTTLPR and response to psychological therapy. Mol Psychiatry 17:236-237.