Research Discussion with ADHD Expert Dr. Stewart Mostofsky

July 2, 2012
Topic: Study finds brain neurotransmitter may be key in ADHD

Dr. Stewart MostofskyChildren diagnosed with attention-deficit hyperactivity disorder (ADHD) have significantly lower concentrations of the main inhibitory neurotransmitter in the brain compared with typically developing children. In a study published in the Archives of General Psychiatry, researchers from the Kennedy Krieger Institute and Cincinnati Children's Hospital Medical Center report finding significantly lower concentrations of Gamma-amniobutyric acid (GABA) in the cerebral cortex of children diagnosed with ADHD, a developmental disorder affecting 3 to 5 percent of children, and defined by increased inattentiveness, hyperactivity and impulsivity. The differences were detected in the region of the brain that controls voluntary movement. This is the first study directly examining GABA concentrations in the brains of children with ADHD.

In the following question and answer session, Dr. Stewart Mostofsky, the study's senior author and Director of the Laboratory for Neurocognitive and Imaging Research at Kennedy Krieger Institute, discusses the findings.

Q: Why did you conduct this study?

Mostofsky: Kennedy Krieger Institute and Cincinnati Children's Hospital published a paper in the February 15, 2011 issue of Neurology that showed children with ADHD had a decrease in brain activity called short interval cortical inhibition (SICI), which is located in the motor cortex, the part of the brain that controls voluntary movement. In the study, SICI was measured using Transcranial Magnetic Stimulation (TMS) to apply mild magnetic pulses for brief durations to trigger muscle activity in the hand.

There is strong evidence that this impaired inhibition (indicated by decreased SICI) is regulated by GABA, a critical neurotransmitter for regulating activity in the cerebral cortex of the brain and principal inhibitory neurotransmitter in the mature brain. As ADHD is a disorder characterized by impaired regulation and selection of behavior, there was reason to expect this might be associated with a deficit in GABA. Given our general suspicion and the specific finding we had using TMS, we pursued an investigation of GABA activity in ADHD using a relatively innovative and novel technique in which GABA is measured using Magnetic Resonance Spectroscopy (MRS). Similar to magnetic resonance imaging (MRI), MRS is a test that uses a magnetic field and radio waves to produce images of the brain.

We used MRS to examine the GABA concentration in a 3cm by 3cm section of the primary sensory motor cortex part of the brain that controls the hand.

Q: How do your findings build upon, or run counter to, prior research from your team or others in the field?

Mostofsky: This is the first study directly examining GABA concentrations in the brains of children with ADHD. As mentioned above, the study does build upon the findings that showed decreased SICI in the same part of the brain.

GABA Levels in Brain

Q: What are the most interesting highlights of the study findings?

Mostofsky: The GABA concentrations were significantly lower in the ADHD children (0.98 ± 0.22 i.u.), compared with the typically developing children (1.34 ± 0.47 i.u.).

GABA Levels in Brain Bar Graph

Q: What will this mean for parents/patients/teachers/ scientists?

Mostofsky: This is a preliminary study with a small number of subjects. Replication in a larger sample size will be important. If replicated, the finding would open avenues for innovative treatment approaches targeting inhibitory GABA transmission.

Q: How will this impact future research or clinical care?

Mostofsky: In order to address these questions, it will first be important to examine if there is an association between GABA levels and measures of impaired behavior and motor control that characterizes ADHD. With this, we will also want to examine for effects of other factors, such as gender, age, and ADHD subtype.

Some initial studies are underway. We are actively pursuing these additional research questions, with a larger sample size including more girls, and are examining measures of behavior impairment in the group, including measures of reduced motor and behavioral control.

This does potentially open up pathways for novel therapeutic approaches in treating ADHD. There are limitations to stimulant therapies currently in use. It's important that we consider alternative therapies, and this research will provide a foundation for pursuing novel approaches to diagnosing and treating ADHD.

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This study was supported by the National Institutes of Health and Johns Hopkins University School of Medicine Institute for Clinical and Translational Research.