Latent class subtyping of attention-deficit/hyperactivity disorder and comorbid conditions
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OBJECTIVE: Genetic studies of attention-deficit/hyperactivity disorder (ADHD) generally use discrete DSM-IV subtypes to define diagnostic status. To improve correspondence between phenotypic variance and putative susceptibility genes, multivariate classification methods such as latent class analysis (LCA) have been proposed. The aim of this study was to perform LCA in a sample of 1,010 individuals from a nationwide recruitment of unilineal nuclear families with at least one child with ADHD and another child either affected or clearly unaffected. METHOD: LCA models containing one through 10 classes were fitted to data derived from all DSM-IV symptoms for ADHD, oppositional defiant disorder, and conduct disorder (CD), as well as seven items that screen for anxiety and depression from the National Initiative for Children's Healthcare Quality Vanderbilt Assessment Scale for Parents. RESULTS: We replicated six to eight statistically significantly distinct clusters, similar to those described in other cross-cultural studies, mostly stable when comorbidities are included. For all age groups, anxiety and depression are strongly related to Inattentive and Combined types. Externalizing symptoms, especially CD, are strongly associated with the Combined type of ADHD. Oppositional defiant disorder symptoms in young children are associated with either conduct disorder or anxiety-related symptoms. CONCLUSIONS: Methods such as LCA allow inclusion of information about comorbidities to be quantitatively incorporated into genetic studies. LCA also permits incorporation of milder but still impairing phenotypes than are allowed using the DSM-IV. Such methods may be essential for analyses of large multicenter datasets and relevant for future clinical classifications. This population-based ADHD classification may help resolve the contradictory results presented in molecular genetic studies.
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LCA has been successfully applied in separate ASD and ADHD research fields and has disclosed clinically relevant, more homogeneous subtypes of both disorders.
“This approach has already been successfully ap-plied in the separate research fields of ASD and ADHD, and has with greater precision disclosed clinically relevant, more homogeneous subtypes of both disorders.[17][18][19]”
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- Authors
- Acosta, M. T., Castellanos, F. X., Bolton, K. L., Balog, J. Z., Eagen, P., Nee, L., Jones, J., Palacio, L., Sarampote, C., Russell, H. F., Berg, K., Arcos-Burgos, M., & Muenke, M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Muenke, Maximilian
- ORCID
- Venue
- Journal of the American Academy of Child & Adolescent Psychiatry
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 47
- Issue
- 7
- Pages
- 797-807
- ISSN
- 0890-8567 (ISSN-L)
- PMC
- PMC2774844
- OpenAlex
- W2065667226
- Cited by
- 82
- References
- 59
- Citations by year
- 2026: 3 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 10 · 2015: 2 · 2014: 8 · 2013: 4 · 2012: 11
- FWCI
- 5.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion, public-domain)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- Funders
- National Institutes of Health (Z99 HG999999)
- National Human Genome Research Institute
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- attention deficit hyperactivity disorder, latent class analysis, ADHD subtypes, comorbidities, oppositional defiant disorder, conduct disorder, anxiety, depression, genetic susceptibility, externalizing problems, phenotypic classification
- MeSH terms
- Adolescent, Anxiety, Attention Deficit Disorder with Hyperactivity, Child, Depression, Female, Humans, Male, Personality Assessment, Psychometrics, United States, Reproducibility of Results, Models, Statistical, Comorbidity, Conduct Disorder, Attention Deficit and Disruptive Behavior Disorders, Diagnostic and Statistical Manual of Mental Disorders
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