A Population-Based Imaging Genetics Study of Inattention/Hyperactivity: Basal Ganglia and Genetic Pathways

Sabine E Mous; Anke R Hammerschlag; Tinca J C Polderman; Frank C Verhulst; Henning Tiemeier; Aad van der Lugt; Vincent W Jaddoe; Albert Hofman; Tonya White; Danielle Posthuma

doi:10.1016/j.jaac.2015.05.018

A Population-Based Imaging Genetics Study of Inattention/Hyperactivity: Basal Ganglia and Genetic Pathways

J Am Acad Child Adolesc Psychiatry. 2015 Sep;54(9):745-52. doi: 10.1016/j.jaac.2015.05.018. Epub 2015 Jun 17.

Affiliations

¹ Erasmus Medical Center, Rotterdam, the Netherlands.
² Erasmus Medical Center, Rotterdam, the Netherlands; VU University, Amsterdam, the Netherlands.
³ VU University.
⁴ Erasmus Medical Center, Rotterdam, the Netherlands; VU University, Amsterdam, the Netherlands; VU Medical Center, Amsterdam, The Netherlands. Electronic address: danielle.posthuma@vu.nl.

PMID: 26299296
DOI: 10.1016/j.jaac.2015.05.018

Abstract

Objective: Although attention-deficit/hyperactivity disorder (ADHD) is 1 of the most common neurodevelopmental disorders, little is known about the neurobiology. Clinical studies suggest basal ganglia morphology plays a role. Furthermore, hyperactivity/impulsivity symptoms have recently been linked to genetic pathways involved in dopamine/norepinephrine and serotonin neurotransmission and neuritic outgrowth. We aimed to assess the association between ADHD symptoms, basal ganglia volume, and the 3 proposed genetic pathways in a pediatric population-based sample. With this, we aimed to investigate the generalizability of earlier clinical findings to the general population.

Method: This study included a population-based sample of 1,871 children with data on ADHD symptoms and genetic data, and 344 children with additional neuroimaging data. Regression analyses between ADHD symptom severity and volumetric data of the basal ganglia were performed. Also, gene-set analyses investigating the association between both ADHD symptom severity and basal ganglia volume with the dopamine/norepinephrine, serotonin, and neuritic outgrowth pathways were performed.

Results: More inattention and hyperactivity/impulsivity symptoms were associated with a smaller volume of the putamen (β = -0.13, p = .034), which was regarded as trend-level after correction for multiple testing. Stratified analyses showed a stronger putamen-hyperactivity association in children with clinical scores, although a similar trend was visible in the nonclinical subsample. The genetic pathways were not related to either ADHD symptoms or basal ganglia volume.

Conclusion: ADHD symptoms were marginally related to putamen volume in our population-based sample. We found no evidence for a role of dopamine/norepinephrine, serotonin, or neuritic outgrowth genetic pathways in ADHD symptom severity.

Keywords: attention-deficit/hyperactivity problems; basal ganglia; gene sets; neuroimaging; neurotransmitter systems.

Publication types

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

MeSH terms

Attention Deficit Disorder with Hyperactivity / genetics*
Behavior Rating Scale
Child
Cohort Studies
Female
Genome-Wide Association Study
Humans
Hyperkinesis / epidemiology*
Impulsive Behavior*
Male
Netherlands
Neuroimaging
Organ Size
Polymorphism, Single Nucleotide*
Psychiatric Status Rating Scales
Putamen / pathology*
Serotonin / metabolism
Severity of Illness Index

Substances

Serotonin