Effects of dopaminergic genes, prenatal adversities, and their interaction on attention-deficit/hyperactivity disorder and neural correlates of response inhibition

Dennis van der Meer, Catharina A. Hartman, Daan van Rooij, Barbara Franke, Dirk J. Heslenfeld, Jaap Oosterlaan, Stephen V. Faraone, Jan K. Buitelaar, Pieter J. Hoekstra

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Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that individuals carrying the ADHD risk alleles of the dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) genes may be especially sensitive to their effects. Methods: Functional MRI data, information on prenatal adversities and genetic data were available for 239 adolescents and young adults participating in the multicentre ADHD cohort study NeuroIMAGE (average age 17.3 yr). We analyzed the effects of DRD4 and DAT1, prenatal exposure to alcohol and smoking and their interactions on ADHD severity, response inhibition and neural activity. Results: We found no significant gene × environment interaction effects. We did find that the DRD4 7-repeat allele was associated with less superior frontal and parietal brain activity and with greater activity in the frontal pole and occipital cortex. Prenatal exposure to smoking was also associated with lower superior frontal activity, but with greater activity in the parietal lobe. Further, those exposed to alcohol had more activity in the lateral orbitofrontal cortex, and the DAT1 risk variant was associated with lower cerebellar activity. Limitations: Retrospective reports of maternal substance use and the cross-sectional study design restrict causal inference. Conclusion: While we found no evidence of gene × environment interactions, the risk factors under investigation influenced activity of brain regions associated with response inhibition, suggesting they may add to problems with inhibiting behaviour.

Original languageEnglish
Pages (from-to)113-121
Number of pages9
JournalJournal of Psychiatry and Neuroscience
Volume42
Issue number2
DOIs
Publication statusPublished - 24 Jan 2017

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Attention Deficit Disorder with Hyperactivity
Dopamine D4 Receptors
Gene-Environment Interaction
Smoking
Alcohols
Genes
Dopamine
Brain
Neural Inhibition
Alleles
Occipital Lobe
Parietal Lobe
Dopamine Plasma Membrane Transport Proteins
Dopamine Receptors
Frontal Lobe
Prefrontal Cortex
Young Adult
Cohort Studies
Cross-Sectional Studies
Mothers

Cite this

van der Meer, Dennis ; Hartman, Catharina A. ; van Rooij, Daan ; Franke, Barbara ; Heslenfeld, Dirk J. ; Oosterlaan, Jaap ; Faraone, Stephen V. ; Buitelaar, Jan K. ; Hoekstra, Pieter J. / Effects of dopaminergic genes, prenatal adversities, and their interaction on attention-deficit/hyperactivity disorder and neural correlates of response inhibition. In: Journal of Psychiatry and Neuroscience. 2017 ; Vol. 42, No. 2. pp. 113-121.
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abstract = "Background: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that individuals carrying the ADHD risk alleles of the dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) genes may be especially sensitive to their effects. Methods: Functional MRI data, information on prenatal adversities and genetic data were available for 239 adolescents and young adults participating in the multicentre ADHD cohort study NeuroIMAGE (average age 17.3 yr). We analyzed the effects of DRD4 and DAT1, prenatal exposure to alcohol and smoking and their interactions on ADHD severity, response inhibition and neural activity. Results: We found no significant gene × environment interaction effects. We did find that the DRD4 7-repeat allele was associated with less superior frontal and parietal brain activity and with greater activity in the frontal pole and occipital cortex. Prenatal exposure to smoking was also associated with lower superior frontal activity, but with greater activity in the parietal lobe. Further, those exposed to alcohol had more activity in the lateral orbitofrontal cortex, and the DAT1 risk variant was associated with lower cerebellar activity. Limitations: Retrospective reports of maternal substance use and the cross-sectional study design restrict causal inference. Conclusion: While we found no evidence of gene × environment interactions, the risk factors under investigation influenced activity of brain regions associated with response inhibition, suggesting they may add to problems with inhibiting behaviour.",
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Effects of dopaminergic genes, prenatal adversities, and their interaction on attention-deficit/hyperactivity disorder and neural correlates of response inhibition. / van der Meer, Dennis; Hartman, Catharina A.; van Rooij, Daan; Franke, Barbara; Heslenfeld, Dirk J.; Oosterlaan, Jaap; Faraone, Stephen V.; Buitelaar, Jan K.; Hoekstra, Pieter J.

In: Journal of Psychiatry and Neuroscience, Vol. 42, No. 2, 24.01.2017, p. 113-121.

Research output: Contribution to JournalArticleAcademicpeer-review

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N2 - Background: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that individuals carrying the ADHD risk alleles of the dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) genes may be especially sensitive to their effects. Methods: Functional MRI data, information on prenatal adversities and genetic data were available for 239 adolescents and young adults participating in the multicentre ADHD cohort study NeuroIMAGE (average age 17.3 yr). We analyzed the effects of DRD4 and DAT1, prenatal exposure to alcohol and smoking and their interactions on ADHD severity, response inhibition and neural activity. Results: We found no significant gene × environment interaction effects. We did find that the DRD4 7-repeat allele was associated with less superior frontal and parietal brain activity and with greater activity in the frontal pole and occipital cortex. Prenatal exposure to smoking was also associated with lower superior frontal activity, but with greater activity in the parietal lobe. Further, those exposed to alcohol had more activity in the lateral orbitofrontal cortex, and the DAT1 risk variant was associated with lower cerebellar activity. Limitations: Retrospective reports of maternal substance use and the cross-sectional study design restrict causal inference. Conclusion: While we found no evidence of gene × environment interactions, the risk factors under investigation influenced activity of brain regions associated with response inhibition, suggesting they may add to problems with inhibiting behaviour.

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