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Meta-Analysis
. 2021 May 1;78(5):519-529.
doi: 10.1001/jamapsychiatry.2020.4799.

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

Mikaïl Nourredine  1   2 , Adrien Gering  3 , Pierre Fourneret  4 , Benjamin Rolland  2   5 , Bruno Falissard  6 , Michel Cucherat  7 , Marie-Maude Geoffray  3   8 , Lucie Jurek  3   8
Affiliations
Meta-Analysis

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

Mikaïl Nourredine et al. JAMA Psychiatry. .

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Nourredine reported receiving nonfinancial support from HAC Pharma and Janssen-Cilag Ltd outside the submitted work. Dr Rolland reported receiving personal fees from Shire plc and nonfinancial support from HAC Pharma during the conduct of the study and personal fees from Indivior plc, Ethypharm, Grünenthal, Jansen Global Services, LLC, Otsuka Pharmaceutical Co, Ltd, Gilead Sciences, Inc, and AbbVie, grants from Camurus AB, Gilead Sciences, Inc, and Merck Sharp & Dohme, and nonfinancial support from Recordati SpA outside the submitted work. Dr Falissard reported receiving personal fees from Eli Lilly and Company, Bristol Myers Squibb, Servier Laboratories, GlaxoSmithKline, HRA Pharma, F. Hoffmann-La Roche AG, Boehringer Ingelheim, Bayer AG, Almirall, SA, Allergan Plc, Stallergenes Greer, Sanofi Genzyme, Pierre Fabre Group, AstraZeneca, Novartis AG, Janssen Global Services, LLC, Astellas Pharma US, Inc, Biotronik, Daiichi Sankyo Company Limited, Gilead Sciences, Inc, Merck Sharp & Dohme, H Lundbeck A/S, Actelion Pharmaceuticals US, Inc, AbbVie, Alnylam Pharmaceuticals, Inc, Amgen, Inc, Biocodex, Biogen, BioSpec, Bioprojet, Biotronik, Celgène Corporation, Chiesi USA, Inc, D&A Pharma, Eisai Co, Ltd, Ethypharm, Laboratoires Genevrier, Grünenthal, IDM Pharma Inc, Idorsia Pharmaceuticals Ltd, Indivior PLC, LÉO Pharma A/S, The Menarini Group, Novo Nordisk A/S, Otsuka Pharmaceutical Co, Ltd, Pfizer, Inc, Recordati SpA, Takeda Pharmaceutical Company Limited, and UCB SA outside the submitted work. Dr Jurek reported receiving personal fees from Servier Laboratories outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart Diagram of Studies Selected for Inclusion in the Systematic Review and Meta-analysis
Figure 2.
Figure 2.. Forest Plot for Studies of the Association of Attention-Deficit Hyperactivity Disorder With Schizophrenia
HR indicates hazard ratio; OR, odds ratio. aIncludes female patients only. bIncludes male patients only.
Figure 3.
Figure 3.. Forest Plot of Subgroup Meta-analysis for Association of Attention-Deficit Hyperactivity Disorder With Psychotic Disorder
Graph shows results of random-effects model. OR indicates odds ratio.
See this image and copyright information in PMC

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