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Methodology and Principal Findings We used a sample of 238 adolescents from a community study characterised by the presence of the short allele of 5-HTTLPR (LL, LS, SS) and the presence or absence of exposure to CA before 6 years of age. We measured cognitive and emotional processing using a set of neuropsychological tasks selected predominantly from the CANTAB® battery.

We found that adolescents homozygous for the short allele (SS) of 5-HTTLPR and exposed to CA were worse at classifying negative and neutral stimuli and made more errors in response to ambiguous negative feedback. In addition, cognitive and emotional processing deficits were associated with diagnoses of anxiety and/or depressions. Citation: Owens M, Goodyer IM, Wilkinson P, Bhardwaj A, Abbott R, Croudace T, et al. (2012) 5-HTTLPR and Early Childhood Adversities Moderate Cognitive and Emotional Processing in Adolescence. PLoS ONE 7(11): e48482.

Editor: Andrew H. Kemp, University of Sydney, Australia Received: March 7, 2012; Accepted: October 2, 2012; Published: November 28, 2012 Copyright: © 2012 Owens et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: IMG, PW, TC, PBJ, and BJS are supported by programme and project grants from the Wellcome Trust (Grant no. 074296), MRC (UK) and NIHR (UK). TC held a Senior Research Fellowship from the Department of Health, UK during this study. BJS is a member of the Behavioural and Clinical Neurosciences Institute, University of Cambridge.

This work was completed within the NIHR Collaborations for Leadership in Applied Health Research and Care (CLAHRC) of which PBJ is Director and IMG and TC are the Adolescent Programme and Methods leaders respectively. The CLAHRC is hosted by the University of Cambridge and the Cambridge and Peterborough NHS Foundation Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: BJS consults for Cambridge Cognition Ltd. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Introduction Allelic variation in the promoter region of the serotonin transporter ( 5-HTTLPR), encoded by a single gene (SLC6A4), is partly responsible for regulating serotonergic (5-hydroxytryptamine, 5-HT) functions in the brain. 5-HTTLPR has been considered functionally bi-allelic, where the short (S) allele of this region is associated with lower transcriptional activity, less 5-HT uptake, binding and lower concentrations,. An in vivo study also showed higher rates of 5-HT uptake in platelets for the long (L) compared to the S allele. More recently, research has suggested that an A>G single-nucleotide polymorphism (SNP; rs25531) makes the L allele function similar to the S allele when it is L G rather than L A,,, although this literature is somewhat inconsistent,. Human brain imaging (PET) findings also suggest that if there are differences they may occur more in moderating neurogenesis or methylation processes than binding as such but the precise mechanisms remain somewhat unclear. Two studies have shown that although the L G and S alleles are functionally similar, the S and L A alleles displayed the lowest and highest functioning, respectively, in absolute terms,. Originally postulated to play a causal role in the development of anxiety-related traits or affective disorder, subsequent research has suggested that 5-HTTLPR has a moderating role in the presence of other factors such as an adverse social environment.

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