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      No Moderating Effect of 5-HTTLPR on Associations Between Antenatal Anxiety and Infant Behavior

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          Abstract

          Objective

          Maternal antenatal anxiety is associated with an increased risk of behavioral disturbances in offspring. Recent work has suggested that the effect of maternal antenatal anxiety on infant temperament at 6 months is moderated by the serotonin transporter polymorphism 5-HTTLPR, with carriers of the short allele more susceptible to the adverse behavioral outcomes of maternal antenatal anxiety. These findings, however, are yet to be replicated and extended beyond infancy. The aim of the current study was to assess this same potential moderator (5-HTTLPR) in a large population-based cohort study, and to determine whether or not the effects persist into childhood and early adolescence.

          Method

          Data from the Avon Longitudinal Study of Children and Parents (ALSPAC) cohort (N = 3,946) were used to assess whether the 5-HTTLPR genotype moderated the association between self-reported maternal antenatal anxiety (Crown Crisp Index) in pregnancy, and child temperament at 6 months (Infant Temperament Questionnaire), and also later behavioral and emotional problems on the Strengths and Difficulties Questionnaire from age 4 to 13 years.

          Results

          We found no evidence to suggest that the 5-HTTLPR polymorphism moderated the effects of maternal antenatal anxiety on infant temperament at 6 months or infant behavioral and emotional problems from childhood through to adolescence.

          Conclusion

          Our results, based on a large prospective community sample that assessed children from infancy to early adolescence, provide a thorough test of, but no evidence for, a genetic moderation of the effects of maternal antenatal anxiety by 5-HTTLPR.

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          Most cited references22

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          In utero programming of chronic disease.

          1. Many human fetuses have to adapt to a limited supply of nutrients. In doing so they permanently change their structure and metabolism. 2. These 'programmed' changes may be the origins of a number of diseases in later life, including coronary heart disease and the related disorders stroke, diabetes and hypertension. 3. This review examines the evidence linking these diseases to fetal undernutrition and provides an overview of previous studies in this area.
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            Problems of reporting genetic associations with complex outcomes.

            Inability to replicate many results has led to increasing scepticism about the value of simple association study designs for detection of genetic variants contributing to common complex traits. Much attention has been drawn to the problems that might, in theory, bedevil this approach, including confounding from population structure, misclassification of outcome, and allelic heterogeneity. Other researchers have argued that absence of replication may indicate true heterogeneity in gene-disease associations. We suggest that the most important factors underlying inability to replicate these associations are publication bias, failure to attribute results to chance, and inadequate sample sizes, problems that are all rectifiable. Without changes to present practice, we risk wastage of scientific effort and rejection of a potentially useful research strategy.
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              Is Open Access

              The links between prenatal stress and offspring development and psychopathology: disentangling environmental and inherited influences

              Background Exposure to prenatal stress is associated with later adverse health and adjustment outcomes. This is generally presumed to arise through early environmentally mediated programming effects on the foetus. However, associations could arise through factors that influence mothers' characteristics and behaviour during pregnancy which are inherited by offspring. Method A ‘prenatal cross-fostering’ design where pregnant mothers are related or unrelated to their child as a result of in vitro fertilization (IVF) was used to disentangle maternally inherited and environmental influences. If links between prenatal stress and offspring outcome are environmental, association should be observed in unrelated as well as related mother–child pairs. Offspring birth weight and gestational age as well as mental health were the outcomes assessed. Results Associations between prenatal stress and offspring birth weight, gestational age and antisocial behaviour were seen in both related and unrelated mother–offspring pairs, consistent with there being environmental links. The association between prenatal stress and offspring anxiety in related and unrelated groups appeared to be due to current maternal anxiety/depression rather than prenatal stress. In contrast, the link between prenatal stress and offspring attention deficit hyperactivity disorder was only present in related mother–offspring pairs and therefore was attributable to inherited factors. Conclusions Genetically informative designs can be helpful in testing whether inherited factors contribute to the association between environmental risk factors and health outcomes. These results suggest that associations between prenatal stress and offspring outcomes could arise from inherited factors and post-natal environmental factors in addition to causal prenatal risk effects.
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                Author and article information

                Journal
                J Am Acad Child Adolesc Psychiatry
                J Am Acad Child Adolesc Psychiatry
                Journal of the American Academy of Child and Adolescent Psychiatry
                Elsevier
                0890-8567
                1527-5418
                1 May 2013
                May 2013
                : 52
                : 5
                : 519-526
                Affiliations
                [a ]University of Oxford
                [b ]Imperial College London
                [c ]University of Rochester Medical Center
                [d ]Leiden University
                [e ]University of Bristol
                [f ]McGill University
                Author notes
                []Correspondence to Elizabeth C. Braithwaite, Department of Psychiatry, Warneford Hospital, Warneford Lane, Oxford, OX3 7JX elizabeth.braithwaite@ 123456psych.ox.ac.uk
                Article
                JAAC730
                10.1016/j.jaac.2013.02.010
                3650562
                23622853
                0fcbf6c8-b476-46ea-9ef0-6229f3fb238e
                © 2013 American Academy of Child & Adolescent Psychiatry.

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 28 February 2013
                Categories
                New Research

                Clinical Psychology & Psychiatry
                5-httlpr,antenatal anxiety,gene-by-environment interaction (g×e),fetal programming,serotonin transporter

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