Role of serotonin in psychiatric and somatic comorbidities of attention-deficit/hyperactivity disorder: a systematic literature review

Introduction: Serotonin is a well-established modulator of various neuropsychological processes, as well as organ and endocrine functioning, and metabolism and homeostasis. Serotonin has been implicated in the neurobiology of attention-deficit/hyperactivity disorder (ADHD). Herein, the evidence for a serotonergic link between psychiatric and somatic comorbidities associated with ADHD was evaluated. Methods: A systematic literature review was conducted of the published literature to identify comorbidities proven to co-occur with ADHD and determine whether there was any serotonergic pathophysiology associated with these comorbidities. The average grade of serotonergic evidence was calculated and plotted alongside the volume of publications for each identified comorbidity. The date of the last search was 7 March 2024. Results: One hundred eighty-two individual comorbidities commonly occurring in ADHD populations were identified; 135 (74.2 %) had evidence for serotonergic pathophysiology, including 91 psychiatric and 44 somatic conditions. The grade of evidence for a serotonergic role in the pathophysiology of a given comorbidity was generally medium to high or high. Conclusions: Findings indicate that serotonin plays a key role, alongside dopamine and norepinephrine, in ADHD neurobiology. Serotonin involvement in physiological functioning suggests that dysregulation is likely to generate a broad spectrum of clinical manifestations, which may account for the unique presentation of neuropsychiatric behaviors and comorbidities found in patients with ADHD.