Dopamine and serotonin genetic risk scores predicting substance and nicotine use in attention deficit/hyperactivity disorder.
Individuals with attention deficit/hyperactivity disorder (ADHD) are at increased risk of developing substance use disorders (SUDs) and nicotine dependence. The co-occurrence of ADHD and SUDs/nicotine dependence may in part be mediated by shared genetic liability. Several neurobiological pathways have been implicated in both ADHD and SUDs, including dopamine and serotonin pathways. We hypothesized that variations in dopamine and serotonin neurotransmission genes were involved in the genetic liability to develop SUDs/nicotine dependence in ADHD. The current study included participants with ADHD (n = 280) who were originally part of the Dutch International Multicenter ADHD Genetics study. Participants were aged 5-15 years and attending outpatient clinics at enrollment in the study. Diagnoses of ADHD, SUDs, nicotine dependence, age of first nicotine and substance use, and alcohol use severity were based on semi-structured interviews and questionnaires. Genetic risk scores were created for both serotonergic and dopaminergic risk genes previously shown to be associated with ADHD and SUDs and/or nicotine dependence. The serotonin genetic risk score significantly predicted alcohol use severity. No significant serotonin × dopamine risk score or effect of stimulant medication was found. The current study adds to the literature by providing insight into genetic underpinnings of the co-morbidity of ADHD and SUDs. While the focus of the literature so far has been mostly on dopamine, our study suggests that serotonin may also play a role in the relationship between these disorders.
Department of Clinical Neuropsychology, VU University Amsterdam, The Netherlands.|Department of Cognitive Neuroscience, Radboud University Medical Centre Nijmegen, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, The Netherlands.
Annabeth P
AP
Groenman
Department of Cognitive Neuroscience, Radboud University Medical Centre Nijmegen, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, The Netherlands.|Institute of Psychiatry, King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, UK.|Karakter, Child and Adolescent Psychiatry University Centre, The Netherlands.
Corina U
CU
Greven
Department of Human Genetics, Radboud University Medical Centre Nijmegen, Donders Institute for Brain, Cognition and Behaviour, The Netherlands.
Marjolein M J
MM
van Donkelaar
Department of Psychiatry, Radboud University Medical Centre Nijmegen, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, The Netherlands.|Nijmegen Institute for Science Practitioners in Addiction (NISPA), The Netherlands.
Arnt
A
Schellekens
Department of Human Genetics, Radboud University Medical Centre Nijmegen, Donders Institute for Brain, Cognition and Behaviour, The Netherlands.
Kimm J E
KJ
van Hulzen
Karakter, Child and Adolescent Psychiatry University Centre, The Netherlands.|Department of Psychiatry, Radboud University Medical Centre Nijmegen, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, The Netherlands.
Nanda
N
Rommelse
Department of Psychiatry, University of Groningen, University Medical Center Groningen, The Netherlands.
Catharina A
CA
Hartman
Department of Psychiatry, University of Groningen, University Medical Center Groningen, The Netherlands.
Pieter J
PJ
Hoekstra
Department of Clinical Neuropsychology, VU University Amsterdam, The Netherlands.
Marjolein
M
Luman
Department of Human Genetics, Radboud University Medical Centre Nijmegen, Donders Institute for Brain, Cognition and Behaviour, The Netherlands.|Department of Psychiatry, Radboud University Medical Centre Nijmegen, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, The Netherlands.
Barbara
B
Franke
Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.|K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Norway.
Stephen V
0000-0002-9217-3982
SV
Faraone
Department of Clinical Neuropsychology, VU University Amsterdam, The Netherlands.
Jaap
J
Oosterlaan
Department of Cognitive Neuroscience, Radboud University Medical Centre Nijmegen, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, The Netherlands.|Karakter, Child and Adolescent Psychiatry University Centre, The Netherlands.
Jan K
JK
Buitelaar
D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology* / Q000235:genetics; D015897:Comorbidity; D004298:Dopamine / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D012307:Risk Factors; D012701:Serotonin / Q000235:genetics*; D019966:Substance-Related Disorders / Q000453:epidemiology* / Q000235:genetics*; D011795:Surveys and Questionnaires; D014029:Tobacco Use Disorder / Q000453:epidemiology / Q000235:genetics; D055815:Young Adult
D012701:Serotonin; D004298:Dopamine
ADHD; adolescence; genetic risk scores; nicotine use; substance use