Brain Differences May Point to Novel Therapies for ADHD, OCD

Liam Davenport

June 22, 2016

Individuals with attention-deficit/hyperactivity disorder (ADHD) have disorder-specific and contrasting structural and functional brain abnormalities in comparison with individuals with   obsessive-compulsive disorder (OCD), an international team of researchers has discovered.

Voxel-based meta-analysis of brain imaging studies showed that ADHD patients have smaller and underfunctioning prefrontal/insula regions, whereas in patients with OCD, those areas are larger   and overfunctioning and may, in turn, be poorly controlled by the medial prefrontal cortex.

Led by Katya Rubia, PhD, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, United Kingdom, the investigators note the findings "stress distinctive striatal and   frontal neurofunctional and neurostructural biomarkers for the two disorders, which could have implications for future differential diagnosis and differential treatment."

In addition to offering the possibility of differential diagnoses for ADHD and OCD, "disorder-specific neurofunctional biomarkers also provide useful targets for treatment with drugs that   target these regions or for nonpharmacological therapies such as fMRI-based neurofeedback, brain stimulation, or cognitive training of functions mediated by these regions."

The research was published online June 8 in JAMA Psychiatry.

Reduced Gray Matter

To examine the structural and functional abnormalities in patients with ADHD and OCD, the team conducted a literature search of the PubMed, Science Direct, Web of Knowledge, and Scopus   databases for whole-brain voxel-based morphometry (VBM) and functional MRI (fMRI) studies in children and adults with the disorders and in control patients.

Investigators performed voxel-wise meta-analysis of whole-brain gray matter volume in assessing fMRI differences between ADHD and OCD using Seed-based d-mapping. Regional structural and   functional abnormalities were assessed in each patient. A quantitative comparison was them made between those regions and the corresponding regions in control persons.

In all, 27 ADHD VBM datasets, which included 931 patients and 822 control persons, and 30 ODC VBM datasets, comprising 928 patients and 942 control persons, were identified. The search also   yielded 33 ADHD fMRI datasets for 489 patients and 591 control persons and 18 OCD fMRI datasets for 287 patients and 284 control persons.

Analysis revealed that ADHD patients had multimodal structural and functional abnormalities in the left and right bilateral basal ganglia/insula consisting of significantly decreased gray   matter volume and function in comparison with both OCD patients and control persons (P < .001 for all). In contrast, OCD patients showed increases in both gray matter volume and function   in the basal ganglia/insula (P < .001).

For ADHD patients, disorder-specific underactivation was found in the right ventrolateral prefrontal cortex and related areas (P < .001), whereas in OCD patients, disorder-specific   reductions in structure and function were found in the rostra and dorsal anterior cingulate/medial prefrontal cortex (P < .001).

The researchers also note that for both sets of patients, there were reductions in gray matter volume in the ventromedial prefrontal cortex in comparison with control indivudals (P <   .001).

Opposite Ends of the Spectrum

Dr Rubia noted that there is "a 30% comorbidity" for ADHD and OCD and said, "So far, no one has studied the comorbid group.

"Given that they have opposite abnormalities, the question is, what's going on in those who have impulsiveness and compulsiveness?" she told Medscape Medical News.

"Also, behaviorally, impulsivity and compulsivity are the opposite ends of the spectrum. You are either super impulsive, or you're super compulsive, but it is interesting that clinically, it   can co-occur, so you can have a child with obsessive symptoms and who at the same time is also inattentive and compulsive," she added.

In light of these findings, Dr Rubia believes that logically, the group to study next would be those with comorbid ADHD and OCD.

She added that she is not aware of any studies that have looked at this patient population and have examined brain abnormalities in these individuals.

An interesting aspect of the findings is that they confirm the rationale for the treatment options in ADHD and OCD.

"Stimulant medication works fantastically for ADHD. It's the best drug we have in psychiatry ― 70% of ADHD children improve if you give them stimulant drugs. But if you give stimulant drugs to   patients with OCD, you make them worse, so our findings are in line with this," she said.

The current findings may also point to novel treatment options for the two conditions.

"At the moment, for example, we are doing fMRI neural feedback in ADHD, where we teach them to upregulate this right prefrontal cortex, which is so underfunctioning, specifically compared to   OCD," Dr Rubia added.

She also noted that inasmuch as the findings in OCD suggest that there are abnormalities in the medial frontal cortex, "I would propose a treatment where you use neural feedback, for example,   to upregulate this medial frontal region, and then you enhance top-down control in this overactive basal ganglia."

Clinical Implications?

Commenting on the findings for Medscape Medical News, Pamelynn Esperanza, MD, assistant professor of psychiatry in the Division of Child and Adolescent Psychiatry at New York–  Presbyterian Hospital and Weill Cornell Medical College, in New York City, noted that "it can be difficult to extrapolate structural findings to therapeutic efficacy.

"However, the fact that the authors show disorder-specific functional/structural brain abnormalities may help explain why the standard therapeutic approach to these disorders is often   different."

On the question of potential brain abnormalities in individuals with comorbid conditions, Dr Esperanza told Medscape Medical News that the "study tested relatively pure diagnoses of ADHD   or OCD."

Nevertheless, she added that "it is possible that a network abnormality that results in ADHD may also increase the probability of OCD, and vice versa, thus explaining how the direction of the   network abnormalities specific to each disorder may also contribute to comorbidity."

Dr Esperanza believes the findings may help clinicians determine the most appropriate treatment for patients.

"Although behavioral changes are the ultimate outcome measure for evaluating treatment efficacy, sometimes behavioral changes take a long time to manifest for any given psychiatric   treatment.

"Knowing that a specific treatment is (or is not) targeting a brain network may be very useful in choosing between alternative therapies. Consequently, a therapy can be fine-tuned to increase   its ability to target that network," she said.

Dr Rubia has received speaker's honoraria from Lilly and Shire and a grant from Lilly for work on another project. No other relevant financial relationships have been reported.

JAMA Psychiatry. Published online June 8, 2016. Abstract

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