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Published Online: 5 April 2019

Neurobiology of Self-Regulation: Longitudinal Influence of FKBP5 and Intimate Partner Violence on Emotional and Cognitive Development in Childhood

Abstract

Objective:

Self-regulation includes the volitional and nonvolitional regulation of emotional, cognitive, and physiological responses to stimulation. It develops from infancy through individual characteristics and the environment, with the stress hormone system as a central player. Accordingly, the authors hypothesized that genes involved in regulating the stress system, such as FK506 binding protein 5 (FKBP5), interact with early-life stress exposure, such as exposure to intimate partner violence (IPV), to predict self-regulation indicators and associated outcomes, including behavioral and learning problems in school.

Methods:

Study participants were a longitudinal birth cohort of 910 children for whom FKBP5 genotypes were available and who were assessed for exposure to IPV during the first 2 years of life as well as multiple measures of self-regulation: stress-induced cortisol reactivity and fear-elicited emotional reactivity at 7, 15, and 24 months, executive function at 36, 48, and 60 months, and emotional and behavioral difficulties and reading and math achievement in school grades 1, 2, and 5. Data were analyzed using longitudinal clustering and ordinal logistic regression procedures followed by mixed linear modeling.

Results:

Children with two copies of a risk FKBP5 haplotype and IPV exposure were significantly more likely to have a developmental trajectory characterized by high, prolonged stress-induced cortisol reactivity and emotional reactivity in toddlerhood, followed by low executive function at school entry and high emotional and behavior problems and low reading ability in the primary school grades.

Conclusions:

The interaction of FKBP5 and IPV affects the physiological response to stress early in life, with consequences for emotional and cognitive self-regulation. Targeting self-regulation may present an early intervention strategy for children facing genetic and environmental risk.

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Supplementary Material

File (appi.ajp.2019.18091018.ds001.pdf)

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 626 - 634
PubMed: 30947533

History

Received: 3 September 2018
Revision received: 19 December 2018
Accepted: 4 February 2019
Published online: 5 April 2019
Published in print: August 01, 2019

Keywords

  1. Early-Life Stress
  2. Self-Regulation
  3. FKBP5
  4. Gene-By-Environment
  5. Biological Markers
  6. Intimate Partner Violence

Authors

Affiliations

Thorhildur Halldorsdottir, Ph.D. [email protected]
The Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich (Halldorsdottir, Kurtoic, Müller-Myhsok, Binder); the Center of Public Health Sciences, University of Iceland, Reykjavík (Halldorsdottir); the Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, U.K. (Müller-Myhsok); the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (Binder); the Department of Applied Psychology, New York University, New York (Blair); the Department of Human Development and Family Studies, Pennsylvania State University, University Park, and the Frank Porter Graham Child Development Institute, University of North Carolina at Chapel Hill (Family Life Project Key Investigators).
Dunja Kurtoic, M.S.
The Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich (Halldorsdottir, Kurtoic, Müller-Myhsok, Binder); the Center of Public Health Sciences, University of Iceland, Reykjavík (Halldorsdottir); the Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, U.K. (Müller-Myhsok); the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (Binder); the Department of Applied Psychology, New York University, New York (Blair); the Department of Human Development and Family Studies, Pennsylvania State University, University Park, and the Frank Porter Graham Child Development Institute, University of North Carolina at Chapel Hill (Family Life Project Key Investigators).
Bertram Müller-Myhsok, Ph.D.
Family Life Project Key Investigators
The Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich (Halldorsdottir, Kurtoic, Müller-Myhsok, Binder); the Center of Public Health Sciences, University of Iceland, Reykjavík (Halldorsdottir); the Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, U.K. (Müller-Myhsok); the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (Binder); the Department of Applied Psychology, New York University, New York (Blair); the Department of Human Development and Family Studies, Pennsylvania State University, University Park, and the Frank Porter Graham Child Development Institute, University of North Carolina at Chapel Hill (Family Life Project Key Investigators).
Elisabeth B. Binder, M.D., Ph.D.
The Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich (Halldorsdottir, Kurtoic, Müller-Myhsok, Binder); the Center of Public Health Sciences, University of Iceland, Reykjavík (Halldorsdottir); the Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, U.K. (Müller-Myhsok); the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (Binder); the Department of Applied Psychology, New York University, New York (Blair); the Department of Human Development and Family Studies, Pennsylvania State University, University Park, and the Frank Porter Graham Child Development Institute, University of North Carolina at Chapel Hill (Family Life Project Key Investigators).
Clancy Blair, Ph.D. [email protected]
The Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich (Halldorsdottir, Kurtoic, Müller-Myhsok, Binder); the Center of Public Health Sciences, University of Iceland, Reykjavík (Halldorsdottir); the Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, U.K. (Müller-Myhsok); the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (Binder); the Department of Applied Psychology, New York University, New York (Blair); the Department of Human Development and Family Studies, Pennsylvania State University, University Park, and the Frank Porter Graham Child Development Institute, University of North Carolina at Chapel Hill (Family Life Project Key Investigators).

Notes

Send correspondence to Dr. Halldorsdottir ([email protected]) and Dr. Blair ([email protected]).

Author Contributions

Drs. Binder and Blair contributed equally to this study.

Competing Interests

Dr. Halldorsdottir receives funding from European Research Council Consolidator Grant 726413. Dr. Müller-Myhsok is a consultant to HMNC Brain Health and is a member of the advisory board of RowAnalytics. Dr. Binder is a co-inventor on a patent on FKBP5, a novel target for antidepressant therapy (European patent 1687443 B1), and receives research funding from Boehringer Ingelheim for a collaboration on functional investigations of FKBP5. The other authors report no financial relationships with commercial interests.

Funding Information

Supported by the National Institute of Child Health and Human Development (grants R01 HD51502 and P01 HD39667), with co‐funding from the National Institute on Drug Abuse and the National Institutes of Health Environmental Influences on Child Health Outcomes (program grant UG3OD023332). Dr. Halldorsdottir was funded in part by a European Research Council Consolidator Grant (StressGene, grant 726413 to Dr. Unnur A. Valdimarsdóttir).

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