Low dopamine function in attention deficit/hyperactivity disorder: should genotyping signify early diagnosis in children?

Postgrad Med. 2014 Jan;126(1):153-77. doi: 10.3810/pgm.2014.01.2735.

Abstract

Attention deficit/hyperactivity disorder (ADHD) is present in 8% to 12% of children, and 4% of adults worldwide. Children with ADHD can have learning impairments, poor selfesteem, social dysfunction, and an increased risk of substance abuse, including cigarette smoking. Overall, the rate of treatment with medication for patients with ADHD has been increasing since 2008, with ≥ 2 million children now being treated with stimulants. The rise of adolescent prescription ADHD medication abuse has occurred along with a concomitant increase of stimulant medication availability. Of adults presenting with a substance use disorder (SUD), 20% to 30% have concurrent ADHD, and 20% to 40% of adults with ADHD have a history of SUD. Following a brief review of the etiology of ADHD, its diagnosis and treatment, we focus on the benefits of early and appropriate testing for a predisposition to ADHD. We suggest that by genotyping patients for a number of known, associated dopaminergic polymorphisms, especially at an early age, misdiagnoses and/or over-diagnosis can be reduced. Ethical and legal issues of early genotyping are considered. As many as 30% of individuals with ADHD are estimated to either have secondary side-effects or are not responsive to stimulant medication. We also consider the benefits of non-stimulant medication and alternative treatment modalities, which include diet, herbal medications, iron supplementation, and neurofeedback. With the goals of improving treatment of patients with ADHD and SUD prevention, we encourage further work in both genetic diagnosis and novel treatment approaches.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Alleles
  • Animals
  • Attention Deficit Disorder with Hyperactivity / diagnosis
  • Attention Deficit Disorder with Hyperactivity / epidemiology
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Autonomic Nervous System Diseases / genetics
  • Catechol O-Methyltransferase / genetics
  • Central Nervous System Stimulants / therapeutic use
  • Diagnosis, Differential
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine beta-Hydroxylase / deficiency
  • Dopamine beta-Hydroxylase / genetics
  • Genetic Testing
  • Genotype
  • Humans
  • Infant, Newborn
  • Monoamine Oxidase / genetics
  • Neonatal Screening / methods
  • Norepinephrine / deficiency
  • Norepinephrine / genetics
  • Polymorphism, Genetic
  • Psychometrics
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D4 / genetics
  • Substance-Related Disorders / diagnosis
  • Substance-Related Disorders / epidemiology

Substances

  • Central Nervous System Stimulants
  • DRD2 protein, human
  • DRD4 protein, human
  • Dopamine Plasma Membrane Transport Proteins
  • Receptors, Dopamine D2
  • Receptors, Dopamine D4
  • Dopamine beta-Hydroxylase
  • Monoamine Oxidase
  • Catechol O-Methyltransferase
  • Dopamine
  • Norepinephrine

Supplementary concepts

  • dopamine beta hydroxylase deficiency