Interaction between SLC6A4 promoter variants and childhood trauma on the age at onset of bipolar disorders

Age at onset (AAO) of bipolar disorders (BD) could be influenced both by a repeat length polymorphism (5HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4) and exposure to childhood trauma. We assessed 308 euthymic patients with BD for the AAO of their first mood episode and ch...

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Main Authors:	Etain, B., Lajnef, M., Henrion, A., Dargél, A.A., Stertz, L., Kapczinski, F., Mathieu, F., Henry, C., Gard, S., Kahn, J. P., Leboyer, M., Jamain, S., Bellivier, F.
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4635347/

id	pubmed-4635347
recordtype	oai_dc
spelling	pubmed-46353472015-11-25 Interaction between SLC6A4 promoter variants and childhood trauma on the age at onset of bipolar disorders Etain, B. Lajnef, M. Henrion, A. Dargél, A.A. Stertz, L. Kapczinski, F. Mathieu, F. Henry, C. Gard, S. Kahn, J. P. Leboyer, M. Jamain, S. Bellivier, F. Article Age at onset (AAO) of bipolar disorders (BD) could be influenced both by a repeat length polymorphism (5HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4) and exposure to childhood trauma. We assessed 308 euthymic patients with BD for the AAO of their first mood episode and childhood trauma. Patients were genotyped for the 5HTTLPR (long/short variant) and the rs25531. Genotypes were classified on functional significance (LL, LS, SS). A sample of 126 Brazilian euthymic patients with BD was used for replication. In the French sample, the correlation between AAO and trauma score was observed only among ‘SS’ homozygotes (p = 0.002) but not among ‘L’ allele carriers. A history of at least one trauma decreased the AAO only in ‘SS’ homozygotes (p = 0.001). These results remained significant after correction using FDR. Regression models suggested an interaction between emotional neglect and ‘SS’ genotype on the AAO (p = 0.009) and no further interaction with other trauma subtypes. Partial replication was obtained in the Brazilian sample, showing an interaction between emotional abuse and ‘LS’ genotype on the AAO (p = 0.02). In conclusion, an effect of childhood trauma on AAO of BD was observed only in patients who carry a specific stress responsiveness-related SLC6A4 promoter genotype. Nature Publishing Group 2015-11-06 /pmc/articles/PMC4635347/ /pubmed/26542422 http://dx.doi.org/10.1038/srep16301 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Etain, B. Lajnef, M. Henrion, A. Dargél, A.A. Stertz, L. Kapczinski, F. Mathieu, F. Henry, C. Gard, S. Kahn, J. P. Leboyer, M. Jamain, S. Bellivier, F.
spellingShingle	Etain, B. Lajnef, M. Henrion, A. Dargél, A.A. Stertz, L. Kapczinski, F. Mathieu, F. Henry, C. Gard, S. Kahn, J. P. Leboyer, M. Jamain, S. Bellivier, F. Interaction between SLC6A4 promoter variants and childhood trauma on the age at onset of bipolar disorders
author_facet	Etain, B. Lajnef, M. Henrion, A. Dargél, A.A. Stertz, L. Kapczinski, F. Mathieu, F. Henry, C. Gard, S. Kahn, J. P. Leboyer, M. Jamain, S. Bellivier, F.
author_sort	Etain, B.
title	Interaction between SLC6A4 promoter variants and childhood trauma on the age at onset of bipolar disorders
title_short	Interaction between SLC6A4 promoter variants and childhood trauma on the age at onset of bipolar disorders
title_full	Interaction between SLC6A4 promoter variants and childhood trauma on the age at onset of bipolar disorders
title_fullStr	Interaction between SLC6A4 promoter variants and childhood trauma on the age at onset of bipolar disorders
title_full_unstemmed	Interaction between SLC6A4 promoter variants and childhood trauma on the age at onset of bipolar disorders
title_sort	interaction between slc6a4 promoter variants and childhood trauma on the age at onset of bipolar disorders
description	Age at onset (AAO) of bipolar disorders (BD) could be influenced both by a repeat length polymorphism (5HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4) and exposure to childhood trauma. We assessed 308 euthymic patients with BD for the AAO of their first mood episode and childhood trauma. Patients were genotyped for the 5HTTLPR (long/short variant) and the rs25531. Genotypes were classified on functional significance (LL, LS, SS). A sample of 126 Brazilian euthymic patients with BD was used for replication. In the French sample, the correlation between AAO and trauma score was observed only among ‘SS’ homozygotes (p = 0.002) but not among ‘L’ allele carriers. A history of at least one trauma decreased the AAO only in ‘SS’ homozygotes (p = 0.001). These results remained significant after correction using FDR. Regression models suggested an interaction between emotional neglect and ‘SS’ genotype on the AAO (p = 0.009) and no further interaction with other trauma subtypes. Partial replication was obtained in the Brazilian sample, showing an interaction between emotional abuse and ‘LS’ genotype on the AAO (p = 0.02). In conclusion, an effect of childhood trauma on AAO of BD was observed only in patients who carry a specific stress responsiveness-related SLC6A4 promoter genotype.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4635347/
_version_	1613498233227575296

Interaction between SLC6A4 promoter variants and childhood trauma on the age at onset of bipolar disorders

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