The attention deficit/hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in children and adolescents. It may persist until the adult age in 30-50% of cases. Among the characteristic traits of the ADHD, there can be found the propensity for risk-taking and the inclination to the abuse of substances and to the gambling. The subjects are generally impulsive and have difficulties in focus their attention for a long time, so they tend to avoid time-consuming activities like planning and strategy development.

These symptoms are known to be related with the disruption of the dopaminergic and serotoninergic systems: low dopamine concentration in the prefrontal brain regions can lead to an increase of glutamate, which is the main excitatory neurotransmitter in the brain. So that, the attention of the researchers has mainly been focused on studying the alterations of the prefrontal lobes and of the striatum, the brain regions more involved in the control of emotions and attention processes. However, a precise diagnosis of the ADHD is still far to be achieved, due to the lack of quantifiable biomarkers. So, the diagnosis is actually based only on assessing the behavior of the subjects and submitting them to interviews.


MR imaging is a useful tool in the study of ADHD biomarkers

Magnetic Resonance (MR) imaging, a non-invasive in vivo technique, may help to detect in specific regions of the subject brain the presence and the possible alterations of molecules involved in the ADHD, that act as potential biomarkers. Among the most important molecules, there can be found glutamate, glutamine, choline, N-acetyl aspartate (NAA), myo-inositol (mIns), and creatine. Even if, in particular conditions, MR can measure the amount of a molecule, it is most common to calculate the ratio between a molecule and the total quantity of creatine or mIns detected. Moreover, the MR can detect the variations of the volume of specific brain regions: for example, children with ADHD suffer a reduction of the cerebrum and cerebellum volume.


MR imaging in animal models

Animal models, in particular rodents – mice and rats – are an important target for MR analysis. Several studies focused on their brain modifications after administration of methylphenidate or atomoxetine, two of the main (and effective) drugs used in ADHD treatment in humans. Some models, for example, have symptoms that resemble the ones of pathologic gamblers: in these rodents, the dopamine transporter is present in higher quantities in the dorsal striatum region, while it is silenced in the ventral striatum region. This pattern corresponds to the one found in persons that obsessively seek strong sensations, unable to control their impulses: the gamblers, indeed.

Another animal model, obtained by giving rats methylphenidate, corresponds to an opposite profile of low impulsivity and low risk-taking, also typical of a class of ADHD subjects. In this case, creatine and taurine, respectively involved in the functionality of the energy system and the synapses, have higher levels in the dorsal striatum, and lower levels in the ventral striatum.

So that, MR imaging is able to detect the variations of metabolites that act as markers in different conditions of the ADHD.


MR imaging in humans

MR in humans undergoes the same principles described in animal models: searching for ADHD markers in different zones of the forebrain. For example, the ratio between glutamine or glutamate and mIns in the anterior cingulate cortex increases in ADHD subjects, and lowers after the administration of methylphenidate. On the other hand, another study revealed that, in the posterior cingulate cortex, the ratio of glutamine or glutamate with mIns is higher in ADHD patients.

Other molecules may have a role in the ADHD: g-amino butyric acid (GABA) reduces its concentration in correspondence with the impulsive behavior; or NAA decreases in the dorsolateral prefrontal cortex and the cerebellum of children. Unfortunately, there are not so many studies available to date, and in some cases, they have problems of reliability.


Final remarks

The main obstacles found so far in the studies describing MR analysis are the insufficient homogeneity of the examined subjects, the different brain regions analyzed at each time, and the use of different spectroscopy techniques. Therefore, a standardization in the study procedures would be necessary in order to strengthen the reliability of MR imaging in the study of biomarkers and structural changes in subjects affected by ADHD or other neurometabolic disorders.



Altabella L. et al. MR Imaging-Detectable Metabolic Alterations in Attention Deficit/Hyperactivity Disorder: From Preclinical to Clinical Studies. AJNR Am J Neuroradiol. 2014 Jun;35(6 Suppl): S55-63.



The elaboration of this post has been financed by the project PI15/01082, as a part of the National Plan of I+D+I and co-financed by the ISCIII – General Deputy Direction for Evaluation and Development of Health Research – and the European Regional Development Fund (ERDF).