Objective: This systematic review investigates the complex relationship between attention deficit hyperactivity disorder (ADHD) and first-episode non-affective psychosis (FEP), focusing on neurodevelopmental, pharmacological and substance use factors that may influence this association. Methods: Following PRISMA guidelines, we conducted a comprehensive literature search across PubMed, Scopus, Web of Science and PsycINFO databases for studies published between January 2001 and June 2024. We included experimental and observational studies examining ADHD and FEP in participants aged ≥ 16 years. Quality assessment was performed using standardised tools specific to each study design. Results: From 1243 initially identified records, 13 studies met inclusion criteria. Five studies addressing neurodevelopmental factors revealed shared neurobiological vulnerabilities between ADHD and psychosis, including impaired cortical inhibition, neurophysiological markers and cognitive deficits. Five pharmacological studies demonstrated that whilst stimulant-induced psychosis can occur, the absolute risk appears low, with amphetamines carrying a 1.65-fold higher risk than methylphenidate. Three studies on substance use patterns showed that ADHD patients with FEP had significantly higher rates of substance use disorders, particularly cannabis use, which was associated with earlier psychosis onset and poorer outcomes. Conclusions: Individuals with ADHD, particularly those with persistent symptoms from childhood and neurocognitive deficits, may have an elevated risk of developing FEP. Substance use appears to be an important mediating factor in this relationship. Regarding pharmacological treatment, recent epidemiological evidence provides a more nuanced perspective on stimulant safety, though the evidence remains mixed and requires further investigation. These findings highlight the importance of comprehensive assessment, substance use prevention and individualised risk stratification when managing ADHD patients at risk for psychosis.
Neurodevelopmental, Pharmacological and Substance Use Factors in the Association Between ADHD and First‐Episode Non‐Affective Psychosis: A Systematic Review
Ricci, Valerio;Di Salvo, Gabriele;Maina, Giuseppe
2026-01-01
Abstract
Objective: This systematic review investigates the complex relationship between attention deficit hyperactivity disorder (ADHD) and first-episode non-affective psychosis (FEP), focusing on neurodevelopmental, pharmacological and substance use factors that may influence this association. Methods: Following PRISMA guidelines, we conducted a comprehensive literature search across PubMed, Scopus, Web of Science and PsycINFO databases for studies published between January 2001 and June 2024. We included experimental and observational studies examining ADHD and FEP in participants aged ≥ 16 years. Quality assessment was performed using standardised tools specific to each study design. Results: From 1243 initially identified records, 13 studies met inclusion criteria. Five studies addressing neurodevelopmental factors revealed shared neurobiological vulnerabilities between ADHD and psychosis, including impaired cortical inhibition, neurophysiological markers and cognitive deficits. Five pharmacological studies demonstrated that whilst stimulant-induced psychosis can occur, the absolute risk appears low, with amphetamines carrying a 1.65-fold higher risk than methylphenidate. Three studies on substance use patterns showed that ADHD patients with FEP had significantly higher rates of substance use disorders, particularly cannabis use, which was associated with earlier psychosis onset and poorer outcomes. Conclusions: Individuals with ADHD, particularly those with persistent symptoms from childhood and neurocognitive deficits, may have an elevated risk of developing FEP. Substance use appears to be an important mediating factor in this relationship. Regarding pharmacological treatment, recent epidemiological evidence provides a more nuanced perspective on stimulant safety, though the evidence remains mixed and requires further investigation. These findings highlight the importance of comprehensive assessment, substance use prevention and individualised risk stratification when managing ADHD patients at risk for psychosis.
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