ADHD and the brain

Attention Deficit Hyperactivity Disorder (ADHD) is a developmental neurological condition affecting functioning in a number of domains, but in particular, the ability to focus and concentrate, and regulate activity levels. This is a common disorder with 2.5-4.0% of adults meeting diagnostic criteria for ADHD (Fayyad et al, 2007), and this condition has significant impact on a persons life, as well as those around them.

The first line treatment for ADHD are medications such as psychostimulants (methylphenidate and amphetamines) and non-stimulants such as atomoxetine. Atomoxetine is a selective noradrenaline reuptake inhibitor (NRI), not to be confused with SNRIs or SSRIs which are popular antidepressants.

In terms of its neuroimaging in Adult ADHD, this is still relatively understudied, especially in the adult population. The few morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) studies available to date have found heterogeneous results and therefore more studies are needed. Despite this, there is preliminary evidence that the neuropathology underlying ADHD in adults may involve abnormalities both of gray matter and white matter tracts.

The aims of the review

The authors of the study point out that there have not been many studies of the neuroanatomical circuity of adults ADHD and specifically, not many that excluded a history of use of stimulant medication. They wanted to address this by conducting the study in such way that only to include people with ADHD who have not been previously treated with stimulants.


Twenty-two treatment-naive patients with ADHD aged 18–50 years were consecutively evaluated at the outpatient ADHD. They were interviewed with the Structured Clinical Interview (SCID) for the DSM-IV and the Schedule for Affective
Disorders and Schizophrenia for school-age children-present and lifetime version (K-SADS-PL) Adapted Module (version 6.0) in order to confirm the diagnosis of ADHD and also to access potential axis I comorbidities. Nineteen healthy volunteers matched for age and gender with ADHD patients were recruited through advertisement in the local community and constituted the healthy control group. All subjects in the control group underwent the same questioning.

All subjects underwent MRI scanning and after the images were segmented into their 3 principal brain tissues (gray matter, white matter and cerebrospinal fluid space) were spatially registered to the single-subject brain template of Montreal Neurological Institute (MNI) which was used to generate mass preserved volumetric maps, named Regional Analysis of Volumes. Examined in Normalized Space (RAVENS) maps of the gray matter, white matter and cerebrospinal fluid compartments were used to calculate tissue density whilst following the spatial normalization, Fractional Anisotropy (FA) and Trace (TR) images were used to calculate the degree of myelination, density and organization of white matter tracts.


In this stimulant naïve sample, the authors reported higher fractional anisotropy in with regards to the white matter of the bilateral superior frontal gyrus, right middle frontal left gyrus, left postcentral gyrus, bilateral cingulate gyrus, bilateral middle temporal gyrus and right superior temporal gyrus for the adult ADHD group.

Furthermore, they also reported reductions in trace (a measure of diffusivity) in ADHD found in fronto-striatal-parieto-occipital circuits, including the right superior frontal gyrus and bilateral middle frontal gyrus, right precentral gyrus, left middle occipital gyrus and bilateral cingulate gyrus, as well as the left body and right splenium of the corpus callosum, right superior corona radiata, and right superior longitudinal and fronto-occipital fasciculi.

Volumetric abnormalities in ADHD subjects were found only at a trend level of significance, including reduced gray matter in the right angular gyrus, and increased gray matter in the right supplementary motor area and superior frontal gyrus.


Part of the white matter tracts in which the authors found the greater degree of difference was between the ones also found to detected trend gray matter volume changes namely the fronto-striatal-parieto-temporo-occipital networks. Therefore, taking together the different gray matter and white matter measurements evaluated in the present study, the findings obtained suggest that the persistence of ADHD symptoms into adulthood relate to circumscribed gray matter volume abnormalities, subtler than those detected in children and adolescent with ADHD.


As found in previous studies, adult ADHD is associated with neuroanatomical abnormalities mainly affecting the white matter microstructure in fronto-parieto-temporal circuits that have been implicated in cognitive, emotional and visuomotor processes. This was found in stimulant naïve patients. In terms of gray matter, there were subtle gray matter volume abnormalities affecting fronto-parietal networks, with a statistical trend towards GM reductions in the right angular gyri in the adult ADHD group.

Citation: Chaim TM, Zhang T, Zanetti MV, da Silva MA, Louzã MR, et al. (2014) Multimodal Magnetic Resonance Imaging Study of Treatment-Naïve Adults with Attention-Deficit/Hyperactivity Disorder. PLoS ONE 9(10): e110199. doi:10.1371/journal.pone.0110199

Dr Adamou’s review for the month of October 2014