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Original Investigation
February 24, 2021

Association of Attention-Deficit/Hyperactivity Disorder in Childhood and Adolescence With the Risk of Subsequent Psychotic Disorder: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Service Hospitalo-Universitaire de Pharmacotoxicologie de Lyon, Hospices Civils de Lyon, Lyon, France
  • 2Service Universitaire d’Addictologie de Lyon, Centre Hospitalier Le Vinatier, Bron, France
  • 3Centre d’Evaluation et de Diagnostic de l’Autisme et Autres Troubles du Neurodéveloppement, Centre Hospitalier Le Vinatier, Bron, France
  • 4Service de Psychopathologie de l’Enfant et du Développement, Hospices Civils de Lyon, Lyon, France
  • 5Université de Lyon, Université Claude Bernard Lyon, Centre de Recherche en Neurosciences de Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM) U1028, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 5292, Psychiatric Disorders: Neuroscience Research And Clinical Research 2, Lyon, France
  • 6Centre de Recherche en Epidémiologie et en Santé des Populations, INSERM U1018, Université Paris-Saclay, Paris, France
  • 7Laboratoire de Biométrie et Biologie Evolutive, Service de Pharmacologie Clinique, UMR CNRS 5558, Lyon, France
  • 8Health Services and Performance Research EA7425, Université Lyon 1, Lyon, France
JAMA Psychiatry. 2021;78(5):519-529. doi:10.1001/jamapsychiatry.2020.4799
Key Points

Question  Does attention-deficit/hyperactivity disorder (ADHD) during childhood increase the risk of subsequent psychotic disorder?

Findings  Pooled estimates from this systematic review and meta-analysis of 12 studies and 1.85 million participants found an increase in the risk of psychotic disorder associated with a diagnosis of ADHD during childhood compared with not having ADHD during childhood.

Meaning  These findings suggest that childhood ADHD is associated with an increased risk of developing a psychotic disorder, and patients need follow-up even after 18 years of age.

Abstract

Importance  Growing evidence supports an association between attention-deficit/hyperactivity disorder (ADHD) in childhood and subsequent psychotic disorders. Both disorders share physiopathological features such as attention deficits, dopaminergic imbalance, and genetic susceptibility. However, the results of epidemiologic studies have been conflicting.

Objective  To provide a quantitative synthesis of studies exploring the association between ADHD and the risk of subsequent psychotic disorder.

Data Sources  A systematic literature search of the MEDLINE, Scopus, PsycInfo, and Web of Science databases was performed from inception until the final analysis on July 7, 2020. No restriction of language was applied.

Study Selection  Cohort and case-control studies examining the relative risk of developing a psychotic disorder in people diagnosed with ADHD at younger than 18 years compared with control individuals without ADHD.

Data Extraction and Synthesis  Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed in reporting results. Two independent reviewers extracted the data and assessed the risk of bias of individual studies using the Newcastle-Ottawa Scale. Preferably adjusted odds ratios (aORs) or hazard ratios from the identified studies were extracted, and ORs were computed when they were not adjusted. A random-effects model was used to calculate the pooled relative effect using the meta package in R.

Main Outcomes and Measures  An association between ADHD (exposure) and psychotic disorder (outcomes); both diagnoses were based on international classification.

Results  A total of 15 studies were included in the review. Twelve studies were pooled in the meta-analysis, representing 1.85 million participants. A diagnosis of ADHD in childhood was associated with a significant increase in the risk of subsequent psychotic disorder, with a pooled relative effect of 4.74 (95% CI, 4.11-5.46; I2 = 43% [95% CI, 0%-70%]). No significant between-group differences were found for subgroup analyses according to psychotic disorder (odds ratio [OR], 5.04; 95% CI, 4.36-5.83) or schizophrenia (OR, 4.59; 95% CI, 3.83-5.50) outcomes, cohort (OR, 4.64; 95% CI, 4.04-5.34) or case-control (OR, 6.81; 95% CI, 4.21-11.03) study design, and adjusted (OR, 4.72; 95% CI, 4.11-5.46) or unadjusted (OR, 3.81; 95% CI, 1.39-10.49) estimates. Meta-regressions were not significant when sex and bias score were used as covariates. No evidence of publication bias was found.

Conclusions and Relevance  These findings suggest that childhood ADHD is associated with an increased risk of a subsequent psychotic disorder. Further studies are required to determine the mechanisms linking these common conditions and whether early intervention for ADHD might reduce the risk of subsequent psychotic disorder.

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