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. 2012 Feb;21(1):9-15.

Maternal Stress during Pregnancy, ADHD Symptomatology in Children and Genotype: Gene-Environment Interaction

Natalie Grizenko  1 , Marie-Eve Fortier, Christin Zadorozny, Geeta Thakur, Norbert Schmitz, Renaud Duval, Ridha Joober
Affiliations

Maternal Stress during Pregnancy, ADHD Symptomatology in Children and Genotype: Gene-Environment Interaction

Natalie Grizenko et al. J Can Acad Child Adolesc Psychiatry. 2012 Feb.

Abstract
in English, French

Objective: Case control studies suggest a relationship between maternal stress during pregnancy and childhood ADHD. However, maternal smoking, parenting style and parental psychiatric disorder are possible confounding factors. Our objective was to control for these factors by using an intra-familial design, and investigate gene-environment interactions.

Methods: One hundred forty two children, ages 6 to 12, (71 with ADHD, and their 71 non-ADHD siblings) participated in the intra-familial study design. A larger sample of ADHD children (N=305) was genotyped for DAT1 and DRD4 to examine gene-environment interactions. Symptom severity was evaluated using the Child Behavior Checklist (CBCL) and the Conners' Global Index for Parents (CGI-P). The Kinney Medical and Gynecological Questionnaire was used to report stressful events during pregnancies.

Results: LOGISTIC REGRESSION INDICATED THAT MOTHERS WERE MORE LIKELY TO HAVE EXPERIENCED HIGH STRESS DURING PREGNANCY OF THEIR ADHD CHILD COMPARED TO THAT OF THE UNAFFECTED SIBLING (OR: 6.3, p=.01). In the larger sample, DRD4 7/7 genotype was associated with increased symptom severity in the high stress pregnancy (p=.01).

Conclusions: Maternal stress during pregnancy was associated with the development of ADHD symptomatology after controlling for family history of ADHD and other environmental factors. This association could partly be mediated through the DRD4 genotype.

Objectifs: Les études de cas-témoins laissent croire qu’il existe une relation entre le stress maternel pendant la grossesse et le TDAH chez les enfants. Cependant, le tabagisme maternel, le style parental et les troubles psychiatriques chez les parents sont des facteurs confondants possibles. L’objectif de notre étude était de contrôler ces facteurs en utilisant une approche intrafamiliale et d’investiguer les interactions entre les gènes et l’environnement.

Méthodologie: Cent quarante-deux enfants âgés de 6 à 12 ans (71 souffrant de TDAH et 71 frères ou soeurs sans TDAH) ont participé à une étude intrafamiliale. Les gènes DAT1 et DRD4 ont été étudiés dans un échantillon plus large d’enfants souffrant de TDAH (N=305) afin d’analyser les interactions gènes-environnement. La gravité des symptômes a été évaluée en se basant sur le Child Behavior Checklist (CBCL) (Liste de vérification du comportement), et sur le Conners’ Global Index for Parents (CGI-P) (Échelle globale d’évaluation Conners – version du parent). Le Kinney Medical and Gynecological Questionnaire a servi à consigner les événements stressants pendant la grossesse.

Résultats: La régression logistique a indiqué qu’il est plus probable que les mères aient subi de hauts niveaux de stress durant la grossesse de leur enfant avec TDAH par rapport à celle de leur frère ou de leur soeur. (OR : 6.3, p=.01). Dans l’échantillon élargi, le génotype DRD4 7/7 a été associé à des symptômes plus graves dans le groupe des mères qui avaient subi un haut niveau de stress durant leur grossesse (p=.01).

Conclusions: Après avoir vérifié les antécédents familiaux de TDAH et certains facteurs environnementaux, nous constatons qu’il existe une relation entre le stress maternel pendant la grossesse et l’apparition des symptômes de TDAH. Cette relation s’exprime en partie à travers le génotype DRD4.

Keywords: ADHD; DRD4; pregnancy; prenatal stress.

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Figures

Figure 1
Figure 1
Symptom severity in children as measured by the CBCL, presented according to the level of prenatal stress and DRD4 genotype. Data analysis showed a significant GxE interaction (p=.01), with children homozygous for the 7-repeat allele being particularly sensitive to high prenatal stress exposure compared to low stress exposure. Mean CBCL total T-score
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