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Am J Med Genet B Neuropsychiatr Genet. 2015 Sep;168(6):480-491. doi: 10.1002/ajmg.b.32340. Epub 2015 Jul 14.

Dopamine receptor DRD4 gene and stressful life events in persistent attention deficit hyperactivity disorder.

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Psychiatric Genetics Unit, Institute Vall d'Hebron Research (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.
Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
AB-Biotics SA, Barcelona, Spain.
Departament de Genètica, Universitat de Barcelona, Catalonia, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain.
Institut de Biomedicina de la Universitat de Barcelona (IBUB), Catalonia, Spain.


We performed a case-control association study in persistent ADHD considering eight candidate genes (DRD4, DAT1/SLC6A3, COMT, ADRA2A, CES1, CYP2D6, LPHN3, and OPRM1) and found additional evidence for the involvement of the Dup 120bp and VNTR 48bp functional variants within the dopamine receptor DRD4 gene in the etiology of adult ADHD. We subsequently investigated the interaction of stressful life events with these two DRD4 polymorphisms, and the impact of such events on the severity of ADHD symptomatology. The gene-by-environment analysis revealed an independent effect of stressful experiences on the severity of persistent ADHD, and a gene-by-environment interaction on the inattentive dimension of the disorder, where non carriers of the Dup 120bp (L) - VNTR 48bp (7R) haplotype were more sensitive to environmental adversity than carriers. These results are in agreement with previous works reporting a relationship between DRD4 and the effect of adverse experiences, which may explain the discordant findings in previous genetic studies and strengthen the importance of gene-by-environment interactions on the severity of ADHD.


ADHD; Attention deficit hyperactivity disorder; DRD4; GxE interaction; Stressful life events


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