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A Neuroimaging Biomarker for ADHD?

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common childhood diseases, diagnosed in 2% to 7% of school-aged children. In the absence of a biomarker to definitively diagnose ADHD, clinicians rely on patient- or family-reported symptoms of inattention or hyperactivity in conjunction with their own evaluation.

Often prescribed to treat ADHD, psychostimulants are thought to increase dopamine levels that are typically depressed in patients with ADHD. Because psychostimulants affect the reward circuitry of the brain, they can be addictive.

When prescribed appropriately by a physician, psychostimulants are safe and effective. In fact, ADHD patients, who are at increased risk of substance abuse, are less likely to develop an addiction if they receive psychostimulant therapy as children.1 Nonetheless, the growing supply of legally prescribed psychostimulants has led to substantial illegal diversion. For example, some students use psychostimulants obtained from friends to improve their focus when studying for tests. A 2013 New York Times article aroused concerns that even legally obtained psychostimulants could have tragic consequences in those misdiagnosed with ADHD, as was the case with an aspiring medical student who took his own life after years of abusing Adderall.2

adhd neuroimaging marker image
FIGURE. Magnetic field correlation (MFC) and relaxation rate R2* parametric maps, masked for regions of interest (globus pallidus, putamen, caudate nucleus, and thalamus), are shown for typically developing controls (TDC), ADHD patients with a history of psychostimulant treatment, and medication-naïve ADHD patients. Qualitative differences between TDC and ADHD subgroups are visible only in the MFC maps, with iron-rich regions indicated in yellow.

That is why news of a possible ADHD neuroimaging biomarker aroused excitement at this year’s meeting of the Radiological Society of North America. An MUSC investigator, Vitria Adisetiyo, PhD, reported the results of a study in which magnetic field correlation (MFC), a new form of magnetic resonance imaging (MRI), was used to measure brain iron levels in 22 children and adolescents with ADHD and 27 healthy age-matched controls. The study showed that medication-naïve patients with ADHD had low levels of brain iron compared with either healthy controls or ADHD patients receiving psychostimulant therapy, providing the first imaging evidence linking iron levels and medication-naïve ADHD and demonstrating the ability of psychostimulants to increase those levels (Figure). “The fact that we can use imaging to measure the biochemical effect of a drug in the brain noninvasively is very significant. And the study results lend credence to the dopamine theory of ADHD,” notes Joseph A. Helpern, PhD, Director of MUSC’s Center for Biomedical Imaging.

Brain iron has been suspected to play a role in ADHD because it is necessary for dopamine synthesis. Conventional MRI, which can be used to detect iron levels by measuring the signal’s relaxation time, has good sensitivity but poor specificity. With MFC, the MRI machine is programmed differently so that it detects brain iron with sensitivity and better specificity. MFC was pioneered by Dr. Helpern and colleague Jens H. Jensen, PhD.3 Because it requires no contrast medium, MFC is safe for use in children.

If larger trials confirm the efficacy of MFC for indirectly measuring brain iron levels, the clinical ramifications could be enormous. “A reliable neuroimaging biomarker for ADHD would represent a critical tool in helping to achieve diagnostic specificity for the condition, while also potentially allowing for further neurobiological evaluation of the course of ADHD and response to treatment,” notes Kevin Gray, M.D., an Associate Professor in MUSC’s Department of Psychiatry and Behavioral Sciences and a coinvestigator on the study.

References

1 Wilens, TE, et al. Stimulants and sudden death: What is a physician to do? 2006; Pediatrics:118:1215-1219.
2 Schwarz A. Drowned in a stream of prescriptions. New York Times. February 2, 2013.
3 Jensen JH, Chandra R, Ramani A, Lu H, Johnson G, Lee SP, Kaczynski K, Helpern JA. Magnetic field correlation imaging. Magn Reson Med 2006 Jun;55(6):1350-1361.