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Author Notes:

Correspondence: Molly Nikolas; Email: nikolasm@msu.edu

Authors' Contributions: MN formulated study hypothesis, participated in data collection, carried out the analyses, and wrote the manuscript draft.

KF oversaw genotyping procedures, obtained funding, aided in hypothesis generation, and provided manuscript revision.

IW provided statistical consultation, formulated data analytic plan, and provided manuscript revision.

KJ completed genotyping assays on the sample.

JTN advised on hypothesis formulation, obtained funding, assisted with data analysis and manuscript revision.

All authors read and approved the final manuscript.

Acknowledgments: The authors wish to thank Stephen Faraone for his comments on an earlier draft of this manuscript.

Disclosures: All authors report no biomedical financial interests or potential conflicts of interest.


Research Funding:

This work was supported by R01MH070004 from the National Institute of Mental Health (PI: K. Friderici), for data collection and laboratory analyses.

Gene × environment interactions for ADHD: synergistic effect of 5HTTLPR genotype and youth appraisals of inter-parental conflict


Journal Title:

Behavioral and Brain Functions


Volume 6, Number 23


Type of Work:

Article | Final Publisher PDF


Background Serotonin genes have been hypothesized to play a role in the etiology of attention-deficit hyperactivity disorder (ADHD); prior work suggests that serotonin may interact with psychosocial stressors in ADHD, perhaps via mechanisms involved in emotional dysregulation. Because the development of behavioral and emotional regulation depends heavily both on the child's experience within the family context and the child's construals of that experience, children's appraisals of inter-parental conflict are a compelling candidate potentiator of the effects of variation within the serotonin transporter gene promoter polymorphism (5HTTLPR) on liability for ADHD. Method 304 youth from the local community underwent a multi-informant diagnostic assessment procedure to identify ADHD cases and non-ADHD controls. Youth also completed the Children's Perception of Inter-Parental Conflict (CPIC) scale to assess appraisals of self-blame in relation to their parents' marital disputes. The trialleic configuration of 5HTTLPR (long/short polymorphism with A> G substitution) was genotyped and participants were assigned as having high (La/La N = 78), intermediate (La/Lg, La/short, N = 137), or low (Lg/Lg, Lg/short, short/short, N = 89) serotonin transporter activity genotypes. Teacher reported behavior problems were examined as the target outcome to avoid informant overlap for moderator and outcome measures. Results Hierarchical linear regression analyses indicated significant 5HTTLPR × self-blame interactions for ADHD symptoms. Examination of the interactions indicated positive relations between reports of self-blame and ADHD symptoms for those with the high and low serotonin activity genotypes. There was no relation between self-blame and ADHD for those with intermediate activity 5HTTLPR genotypes. Conclusion Both high and low serotonergic activity may exert risk for ADHD when coupled with psychosocial distress such as children's self-blame in relation to inter-parental conflict. Results are discussed in relation to the role of serotonin in the etiology of the ADHD and related externalizing behaviors.

Copyright information:

© 2010 Nikolas et al; licensee BioMed Central Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 2.0 Generic License (http://creativecommons.org/licenses/by/2.0/).

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