When talking about neurotransmitters involved in ADHD, dopamine is a primary candidate for discussion. In fact, most medications today target dopamine and its transporters to treat ADHD symptoms. However, a lesser studied relationship between ADHD and serotonin may be changing the way ADHD medications are made.
Serotonin is an inhibitory neurotransmitter that promotes a calming effect in the brain and body. Impulsivity and hyperactivity are two core concerns associated with ADHD; thus, researchers began investigating serotonin’s influence on moderating these behaviors. The majority of research has found low serotonergic activity to result in more aggressive behavior and impulsive actions.[i]
Serotonin’s Surprise Effect
While dopamine is necessary for motivation and focus maintenance, excess may lead to hyperactivity and restlessness. It was previously believed that Ritalin (a commonly prescribed stimulant for treatment of ADHD) solely relied on increasing dopamine transporter (DAT) to remove excess dopamine from extracellular space in the brain. However, a study at Duke University found that mice still responded to Ritalin with no DAT. It appeared that Ritalin was effective by increasing serotonin levels, producing a calming effect on the mice and improving undistracted performance.[ii] A following study found that this may work through the serotonin receptor 5-HT2A. When these receptors are inhibited by antagonists, dopamine-induced hyperactivity in mice was reduced.[iii]
Contrary to popular belief, dopamine and norepinephrine may not be the only important neurotransmitters involved in hyperactivity and restlessness associated with ADHD. Monitoring neurotransmitter levels in patients with ADHD is a crucial part of understanding where related symptoms may be stemming from.
[i] Nikolas M et al. Gene x environment interactions for ADHD: synergistic effect of 5HTTLPR genotype and youth appraisals of inter-parental conflict. Behavioral and Brain Functions. 2010; 6: 23.
[ii] Gainetdinov RR, Wetsel WC, Jones SR, Levin ED, Jaber M, Caron MG. Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science 1999; 283: 397–401.
[iii] Quist et al. Evidence for the serotonin HTR2A receptor gene as a susceptibility factor in attention deficit hyperactivity disorder (ADHD). Molecular Psychiatry. 2000; 5: 537-541.