Attention-deficit hyperactivity disorder (ADHD) affects more than 5% of children and continues to impact individuals throughout life. Research is being conducted to better understand the potential mechanisms underlying ADHD to help with the development of more effective therapies. Imbalances in neurotransmitters, such as dopamine, noradrenaline, and glutamate are among the potential areas of interest. Recent research is also pointing to the potential role of the GABAergic system in ADHD development.

ADHD generally involves increased inattentiveness, hyperactivity, and impulsivity. Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter, binding to two main receptor types: GABAA and GABAC. It plays a role by inducing sleep, calmness, and relaxation, and it may regulate behavioral inhibition. GABA helps to balance the exhibitory neurotransmitter, glutamate. The balance between GABA and glutamate promotes normal neurological development. An imbalance between the two may contribute to the development of ADHD. Variations in the genes for glutamate and GABA have been shown to correlate with ADHD, including symptom severity. 

GABA may affect the development of ADHD in ways beyond its balancing role of glutamate. The inhibition of GABA may help to filter sensory information and support the selection of appropriate behavioral responses. It may also affect impulsivity and self-control. One study on healthy men using magnetic resonance spectroscopy (MRS) to measure GABA in the dorsolateral prefrontal cortex found that higher levels of GABA led to lower urgency and more self-control. 

Studies have looked more closely at the relationship between GABA and the development of ADHD in childhood. A case-control study evaluated the motor development, motor cortex physiology, and behavioral systems in 49 children with ADHD and 49 age-matched controls. The researchers found a significantly diminished short interval cortical inhibition (SICI) in the dominant motor cortex in the children with ADHD. There was also an association between reduced SICI and motor skills development, along with symptom severity. Dopaminergic and GABAA agonists upregulate SICI. The GABAA-mediated inhibition in the primary motor cortex may lead to SICI. GABAergic interneurons create inhibition that dopamine modulates to increase the signal-to-noise ratio in the frontal cortex. This demonstrates the potential for the GABAergic system to be involved in ADHD. 

Another study looked at the GABA levels in children aged 8 to 12 years with diagnosed ADHD compared to a control group. The researchers used MRS to measure GABA concentration in the 32 participants. They found that the children with ADHD had a reduction of GABA concentrations compared to the control group.

Research to determine the mechanisms behind ADHD, including the role of the GABAergic system, remains ongoing, but studies demonstrate the potential for GABA involvement. A healthy diet and lifestyle may support neurotransmitter balance, including the balance between glutamate and GABA. This may promote healthy neurological development and decrease the risk of associated neurological conditions, such as ADHD. Some individuals may find benefit in supporting GABA levels through targeted nutrient support and/or supplemental GABA.

By Kendra Whitmire, MS, CNS