Metabolic Dysregulation in ADHD: Implications for Appetite, Sleep, Stress Reactivity, and Pharmacological Treatment
Abstract
Background: Attention-deficit/hyperactivity disorder (ADHD) has traditionally been understood through executive and frontostriatal models, but increasing evidence suggests that metabolic, inflammatory, circadian, and neuroendocrine mechanisms may also contribute to clinical heterogeneity. The hypothalamus is a central regulatory hub for appetite, sleep-wake organization, stress responsivity, autonomic function, and endocrine signalling. Objective: This review evaluated evidence linking ADHD with hypothalamic inflammation and related metabolic, inflammatory, circadian, and neuroendocrine dysregulation, with particular emphasis on appetite regulation, sleep and circadian function, stress reactivity, and pharmacological treatment response and tolerability. Methods: A systematic literature search was conducted in PubMed/MEDLINE, Embase, PsycINFO, Scopus, and Web of Science Core Collection from database inception to 31 May 2026. Human observational and intervention studies formed the primary evidence base. Evidence was synthesized narratively. Where available, quantitative findings from previously published meta-analyses were summarized to provide an overview of the strength and consistency of the evidence. Results: The reviewed evidence indicates that ADHD is associated with increased obesity risk, altered appetite-related hormones, immune-inflammatory changes, delayed circadian timing, atypical cortisol responsivity, and treatment-related effects on appetite, sleep,…
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