Magnetic resonance spectroscopy studies of attention deficit hyperactivity disorder

Abstract

Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed pediatric psychiatric disorder and often persists into adulthood. As its name implies, the core symptoms of ADHD are habitual and impairing inattention, hyperactivity, and impulsivity. Chronic oral stimulants and other drugs are frequently effective in relieving symptoms of ADHD, though poor lifetime outcomes remain common. Neuroimaging in several modalities suggests dysfunction in various cingulate subregions, prefrontal cortices, basal gangliar nuclei, and the cerebellum in ADHD. Physiologic changes in these regions may also accompany pharmacologic treatment response. We review the literature to date, including drug studies, concerning in vivo magnetic resonance spectroscopy (MRS) of the brain in pediatric and adult ADHD. MRS reveals effects of ADHD or its treatment in the same brain regions as other imaging modalities. Variously across studies, results imply abnormal regional levels of the 1H MRS metabolites N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (NAA + NAAG), glutamate + glutamine (Glx), creatine + phosphocreatine (Cr + PCr), and choline compounds (Cho) that may also be influenced by pharmacotherapies. A number of MRS findings are compatible with the astroglial brain-energy deficiency hypothesis of ADHD. Many MRS studies of ADHD suffer from low subject numbers (<20 per group), partial-voluming of MRS acquisition voxels, and use of ratios to Cr + PCr, among other weaknesses. Future high magnetic-field investigations, including with magnetic resonance spectroscopic imaging (MRSI), on larger, better-balanced subject samples may yield higher spatial and spectral resolution and absolute quantitation of metabolite levels. A speculative cortical glutamate-based cingulocentric model of ADHD is offered that seeks to explain its dynamic symptomatic phenomenology in MRS-relevant neurochemical terms.