Serotonin tranporter methylation and response to cognitive behaviour therapy in children with anxiety disorders
Open accessAbstract
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.
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Patients who showed continued symptom improvement six months after psychotherapy cessation were characterized by a significant increase in average SLC6A4 promoter methylation relative to those who did not improve or worsened at follow-up.
“Of note, patients who showed continued symptom improvement six months after psychotherapy cessation were characterized by a significant increase in average SLC6A4 promoter methylation relative to those who did not improve or worsened at follow-up (Roberts et al., 2014).”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Roberts et al., 2014
The Results report a significant difference in average SERT promoter methylation change between children whose symptoms continued to improve over the six-month follow-up and those who did not improve or worsened. But methylation change was measured during CBT, from pre- to posttreatment, not after therapy ceased; the passage also does not establish a significant increase within the continuing-improvement group. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSLC6A4 methylation is decreased in non-responders post-CBT.
“↓ Methylation in non-responders post-CBT”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Roberts et al., 2014
The Results report that methylation at SERT CpG site 4 decreased from before to after CBT in children classified as nonresponders at follow-up. The claim omits that site and follow-up classification: when children were classified by response immediately after treatment, responders and nonresponders did not differ significantly in methylation change. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn 116 children with mixed anxiety disorders following CBT, treatment non-responders were characterized by a decrease in methylation as driven by a single CpG site in the promoter region of SLC6A4 post-treatment, while treatment responders-although not statistically significant-displayed a small increase in methylation at the same site on a descriptive level.
“In 116 children with mixed anxiety disorders following CBT, treatment non-responders were characterized by a decrease in methylation as driven by a single CpG site in the promoter region of the SLC6A4 gene post-treatment, while in turn, treatment responders -although not statistically significant -displayed a small increase in methylation at the same site on a descriptive level.”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Roberts et al., 2014
SLC6A4 methylation is increased in responders at follow-up.
“↑ Methylation in responders at FU”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Roberts et al., 2014
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- Authors
- Roberts, S., Lester, K. J., Hudson, J. L., Rapee, R. M., Creswell, C., Cooper, P. J., Thirlwall, K. J., Coleman, J. R. I., Breen, G., Wong, C. C. Y., & Eley, T. C.
- Affiliations
- King's College London (GB)
- Macquarie University (AU)
- University of Reading (GB)
- Stellenbosch University (ZA)
- Corresponding author
- Eley, T C
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2014-09-16
- Volume
- 4
- Issue
- 9
- Pages
- e444-e444
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC4203012
- OpenAlex
- W2084286303
- Cited by
- 118
- References
- 13
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 10 · 2022: 7 · 2021: 8 · 2020: 18 · 2019: 13 · 2018: 12 · 2017: 15 · 2016: 17 · 2015: 7 · 2014: 1
- FWCI
- 5.47
- Type
- journal article
- Language
- en
- Update notices
- erratum (2014-10-14)
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CentAUR (University of Reading) (submittedVersion, cc-by)
- Sussex Research Online (University of Sussex) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Funders
- Alexander von Humboldt-Stiftung
- South London and Maudsley NHS Foundation Trust
- National Institute for Health and Care Research (RP_2014-04-018, PB-PG-0110-21190, PB‐PG‐0107‐12042)
- King's College London
- Medical Research Council (G0901874/1, G0901874, MR/J011762/1, G0601874, G0802326)
- Australian Research Council (DP0878609)
- National Health and Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- serotonin transporter, DNA methylation, cognitive behavioral therapy, treatment response, childhood anxiety disorders, epigenetics, CpG sites, treatment-resistant anxiety
- MeSH terms
- Adolescent, Anxiety Disorders, Child, Female, Humans, Male, Cognitive Behavioral Therapy, Treatment Outcome, DNA Methylation, Serotonin Plasma Membrane Transport Proteins
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