Serotonin transporter [corrected] methylation and response to cognitive behaviour therapy in children with anxiety disorders

S Roberts, K J Lester, J L Hudson, R M Rapee, C Creswell, P J Cooper, K J Thirlwall, J R I Coleman, G Breen, C C Y Wong, T C Eley, S Roberts, K J Lester, J L Hudson, R M Rapee, C Creswell, P J Cooper, K J Thirlwall, J R I Coleman, G Breen, C C Y Wong, T C Eley

Abstract

Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35-45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT.

Figures

Figure 1
Figure 1
Change in DNA methylation from pre- to posttreatment in treatment repsonders and nonresponders by CpG site. (a) Primary anxiety responders, *P<0.05. (b) All anxiety responders **P=0.004, ***P=0.002.

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