title: A Population-Based Imaging Genetics Study of Inattention/Hyperactivity: Basal Ganglia and Genetic Pathways.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Sabine E
authors: SE
authors: Mous
authors: Erasmus Medical Center, Rotterdam, the Netherlands; VU University, Amsterdam, the Netherlands.
authors: Anke R
authors: AR
authors: Hammerschlag
authors: VU University.
authors: Tinca J C
authors: TJ
authors: Polderman
authors: Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Frank C
authors: FC
authors: Verhulst
authors: Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Henning
authors: H
authors: Tiemeier
authors: Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Aad
authors: A
authors: van der Lugt
authors: Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Vincent W
authors: VW
authors: Jaddoe
authors: Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Albert
authors: A
authors: Hofman
authors: Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Tonya
authors: T
authors: White
authors: Erasmus Medical Center, Rotterdam, the Netherlands; VU University, Amsterdam, the Netherlands; VU Medical Center, Amsterdam, The Netherlands. Electronic address: danielle.posthuma@vu.nl.
authors: Danielle
authors: D
authors: Posthuma
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D000067290:Behavior Rating Scale; D002648:Child; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D006948:Hyperkinesis / Q000453:epidemiology*; D007175:Impulsive Behavior; D008297:Male; D009426:Netherlands; D059906:Neuroimaging; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D011699:Putamen / Q000473:pathology*; D012701:Serotonin / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D012701:Serotonin
keywords: attention-deficit/hyperactivity problems; basal ganglia; gene sets; neuroimaging; neurotransmitter systems