Prefrontal grey and white matter neurometabolite changes after atomoxetine and methylphenidate in children with attention deficit/hyperactivity disorder: a (1)H magnetic resonance spectroscopy study

Psychiatry Res. 2014 Apr 30;222(1-2):75-83. doi: 10.1016/j.pscychresns.2014.03.003. Epub 2014 Mar 15.

Abstract

Attention deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral childhood disorder. Dysfunction of prefrontal neural circuits which are responsible for executive and attentional functions has been previously shown in ADHD. We investigated the neurometablite changes in areas included in dorsolateral prefrontal neural circuits after 2 months of long-acting methylphenidate or atomoxetine medication in children with ADHD who were responders to treatment. Twenty-one ADHD children were examined by single voxel (1)H-magnetic resonance spectroscopy (MRS) before and after 2 months of medication with OROS methylphenidate (n=10) or atomoxetine (n=11). The spectra were taken from the dorsolateral prefrontal cortex (DLPFC, 8ml) and white matter behind the DLPFC (anterior semioval center, 7.5ml), bilaterally. NAA and NAA/Cr (N-acetylaspartate/creatine) decreased in the left DLPFC and Cho/Cr (choline/creatine) increased in the right DLPFC after atomoxetine medication. Glu+Gln and Glu+Gln/Cr (glutamate/glutamine) increased in the left white matter after methylphenidate medication. We hypothesize that atomoxetine could decrease hyperactivation of DLPFC neurons and methylphenidate could lead to increased activation of cortical glutamatergic projections with the consequences of increased tonic dopamine release in the mesocortical system.

Keywords: Choline; Glutamate; N-Acetylaspartate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic Uptake Inhibitors / pharmacology
  • Adrenergic Uptake Inhibitors / therapeutic use*
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Atomoxetine Hydrochloride
  • Attention / drug effects
  • Attention / physiology
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / metabolism
  • Central Nervous System Stimulants / pharmacology
  • Central Nervous System Stimulants / therapeutic use*
  • Child
  • Choline / metabolism
  • Creatine / metabolism
  • Female
  • Glutamic Acid / metabolism
  • Glutamine / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Methylphenidate / pharmacology
  • Methylphenidate / therapeutic use*
  • Nerve Fibers, Myelinated / drug effects
  • Nerve Fibers, Myelinated / metabolism
  • Nerve Fibers, Unmyelinated / drug effects
  • Nerve Fibers, Unmyelinated / metabolism
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism
  • Propylamines / pharmacology
  • Propylamines / therapeutic use*
  • Treatment Outcome

Substances

  • Adrenergic Uptake Inhibitors
  • Central Nervous System Stimulants
  • Propylamines
  • Glutamine
  • Methylphenidate
  • Aspartic Acid
  • Glutamic Acid
  • Atomoxetine Hydrochloride
  • N-acetylaspartate
  • Creatine
  • Choline