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

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.