A neuroimaging study of adolescents with ADHD found that glutamate levels in the medial prefrontal cortex region of these individuals’ brains increased with age. In contrast, in individuals who experienced remission of ADHD symptoms and in participants who had never suffered from ADHD, glutamate levels in this region of the brain decreased with age. The paper was published in translational psychiatry.
ADHD, or attention-deficit/hyperactivity disorder, is a neurodevelopmental disorder whose main symptoms are inattention, hyperactivity, and impulsivity. It usually begins in childhood. However, in most cases, ADHD is diagnosed when a child starts school, and ADHD symptoms begin to conflict with school rules. Children are usually expected to pay attention and sit quietly in their assigned seats. As a result of this conflict, many ADHD patients have poor academic performance.
People with ADHD tend to have difficulty organizing tasks, managing time, following instructions, and staying focused. They may also interrupt others, act without considering the consequences, and become unusually restless. Symptoms can vary widely, and some people may not have overt hyperactivity, but instead primarily have decreased attention span. Although the onset of ADHD is strongly influenced by genetic and neurological factors, environmental factors can influence the severity of symptoms. For some people, symptoms of ADHD remit as they grow older, but for others, symptoms persist into adulthood.
Study author Marin Bouissi Kovar and her colleagues note that dysregulation of specific systems in the brain appears to be associated with ADHD. Previous studies have already suggested that dysregulation of systems based on the neurotransmitters dopamine and noradrenaline is involved in this disease. New findings indicate that glutamate, the brain’s main excitatory neurotransmitter, may also play a role.
They conducted a neuroimaging study that focused on glutamate levels in the medial prefrontal cortex region of the brains of young people with ADHD. The authors noted that the medial prefrontal cortex mediates cognitive processes related to ADHD, including attention allocation, decision making, and emotion regulation. The neural circuits that use glutamate in the prefrontal cortex also interact with the catecholaminergic system (based on dopamine and noradrenaline), which is known to play a role in shaping ADHD symptoms.
For their analysis, the study authors selected participants from an existing longitudinal cohort study (neurobehavioral clinical research study) for which glutamate concentration data obtained using brain proton magnetic resonance spectroscopy was available.
Overall, participants were 161 adolescents. Of these, 69 had persistent ADHD, 20 had remitting ADHD, and 72 had no ADHD at all. Participants with remitting ADHD were individuals who exhibited symptoms of ADHD at the beginning of the study but did not exhibit symptoms at later assessments. The average age of participants was 14 to 15 years. Most of them were boys: 80% in the persistent ADHD group, 75% in the remitting ADHD group, and 64% in the non-ADHD group.
Study participants completed proton magnetic resonance spectroscopy and magnetic resonance imaging of the brain. Almost half of the participants also completed a follow-up scan, usually about two years later.
The results showed that participants with persistent ADHD and those without ADHD or with remitting ADHD exhibited different developmental trajectories with respect to glutamate levels in the medial prefrontal cortex. Participants with persistent ADHD had increased glutamate concentrations in this region of the brain as they aged. On the other hand, participants with remitting ADHD and those who had never had ADHD showed age-related declines in glutamate levels in the same regions. The researchers believe this may mean that persistent ADHD is associated with delayed or altered neurodevelopmental processes, whereas remitted ADHD reflects the typical, healthy maturation of the brain as it enters adolescence.
Additionally, changes in prefrontal glutamate concentrations in the persistent ADHD group were associated with changes in intrinsic connectivity between the default mode network (a network of brain cells active at rest, including the medial prefrontal cortex) and subcortical regions of the brain. Intrinsic connectivity is the degree to which the spontaneous activity patterns of two neural networks or brain regions are synchronized or correlated when a person is not performing a specific task.
“These findings may indicate altered maturation of glutamate in the medial prefrontal cortex in young people with persistent ADHD,” the study authors concluded.
This study contributes to scientific knowledge about ADHD. However, it should be noted that the cross-sectional and longitudinal design of this study does not allow definitive causal inferences to be drawn from the results. Additionally, the specific scan sequence used limited this study to a single, predefined brain region and did not take into account hormonal fluctuations during adolescence, which may also affect brain maturation.
The paper, “Developmental trajectories of glutamate and the variable clinical course of ADHD in youth,” was authored by Marine Bouissi-Kobar, Yan Zhang, Luke Norman, Saadia Choudhury, Wendy Sharp, Gustavo Sudre, Tonya White, and Philip Shaw.
