ADHD co-morbidities: A review of implication of gene × environment effects with dopamine-related genes

Margus Kanarik; Oliver Grimm; Nina Roth Mota; Andreas Reif; Jaanus Harro

doi:10.1016/j.neubiorev.2022.104757

ADHD co-morbidities: A review of implication of gene × environment effects with dopamine-related genes

Neurosci Biobehav Rev. 2022 Aug:139:104757. doi: 10.1016/j.neubiorev.2022.104757. Epub 2022 Jun 29.

Authors

Margus Kanarik¹, Oliver Grimm², Nina Roth Mota³, Andreas Reif², Jaanus Harro⁴

Affiliations

¹ Chair of Neuropsychopharmacology, Institute of Chemistry, University of Tartu, Ravila 14A Chemicum, 50411 Tartu, Estonia.
² Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, Germany.
³ Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
⁴ Chair of Neuropsychopharmacology, Institute of Chemistry, University of Tartu, Ravila 14A Chemicum, 50411 Tartu, Estonia; Psychiatry Clinic, North Estonia Medical Centre, Paldiski Road 52, 10614 Tallinn, Estonia. Electronic address: Jaanus.Harro@ut.ee.

PMID: 35777579
DOI: 10.1016/j.neubiorev.2022.104757

Abstract

ADHD is a major burden in adulthood, where co-morbid conditions such as depression, substance use disorder and obesity often dominate the clinical picture. ADHD has substantial shared heritability with other mental disorders, contributing to comorbidity. However, environmental risk factors exist but their interaction with genetic makeup, especially in relation to comorbid disorders, remains elusive. This review for the first time summarizes present knowledge on gene x environment (GxE) interactions regarding the dopamine system. Hitherto, mainly candidate (GxE) studies were performed, focusing on the genes DRD4, DAT1 and MAOA. Some evidence suggest that the variable number tandem repeats in DRD4 and MAOA may mediate GxE interactions in ADHD generally, and comorbid conditions specifically. Nevertheless, even for these genes, common variants are bound to suggest risk only in the context of gender and specific environments. For other polymorphisms, evidence is contradictory and less convincing. Particularly lacking are longitudinal studies testing the interaction of well-defined environmental factors with polygenic risk scores reflecting the dopamine system in its entirety.

Keywords: ADHD; Co-morbidity; Dopamine; Environment; Gene.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Attention Deficit Disorder with Hyperactivity* / epidemiology
Attention Deficit Disorder with Hyperactivity* / genetics
Comorbidity
Dopamine / genetics
Dopamine Plasma Membrane Transport Proteins / genetics
Genetic Predisposition to Disease / genetics
Humans
Morbidity
Receptors, Dopamine D4* / genetics

Substances

Dopamine Plasma Membrane Transport Proteins
Receptors, Dopamine D4
Dopamine