ADHD is a disabling neuropsychiatric disorder with high prevalence and a detailed pathogenesis that remains to be elucidated. All medications currently approved to treat ADHD are thought to exert therapeutic effects by manipulation of norepinephrine and/or dopamine. Given the efficacy of ADHD psychostimulant treatment, dopaminergic and noradrenergic neurotransmission is thought to be the main biological substrate of ADHD. However, several lines of evidence also suggest an involvement of serotonin in aspects of the disorder. For example, emotional dysregulation with mood swings and irritability, closely linked to serotonergic pathways, has lately been discussed as an additional core symptom of ADHD, and impulsivity, which is a core diagnostic feature in ADHD, is modulated by serotonin signaling. The serotonin 1B (5-HT1B) receptor is a likely substrate through which serotonin may influence reward and impulsive action. Striatal 5-HT1B receptors are critical for the modulation of impulsive action, possibly through modulation of reward value by interactions with dopamine signaling. This raises the question whether the attenuated dopamine function and reward processing in ADHD can be attributed to alterations in 5-HT1B receptor levels.

The aim of this project is to investigate whether 5-HT1B receptor levels are altered in people with ADHD and whether these alternations can be attributed to interactions with dopamine signaling. Moreover, the project aims to investigate whether 5-HT1B receptors and DAT are related to ADHD symptom severity, brain activity measured with fMRI and neuropsychological functions known to be disturbed in ADHD, such as reward processing, response inhibition and impulsivity.

In this project, 30 unmedicated ADHD patients and 30 control subjects will undergo an investigational program including neuroimaging with PET, SPECT and fMRI, psychiatric and medical assessment, self-report questionnaires and neuropsychological testing.

The project is led by Principal Investigator Sofi da Cunha.