Multilevel analysis of ADHD, anxiety and depression symptoms aggregation in families


A strong genetic role in the etiology of attention-deficit hyperactivity disorder (ADHD) has been demonstrated by several studies using different methodologies. Shortcomings of genetic studies often include the lack of golden standard practices for diagnosis for ADHD, the use of categorical instead of a dimensional approach, and the disregard for assortative mating phenomenon in parents. The current study aimed to overcome these shortcomings and analyze data through a novel statistical approach, using multilevel analyses with Bayesian procedures and a specific mathematical model, which takes into account data with an elevated number of zero responses (expected in samples with few or no ADHD symptoms). Correlations of parental clinical variables (ADHD, anxiety and depression) to offspring psychopathology may vary according to gender and type of symptoms. We aimed to investigate how those variables interact within each other. One hundred families, comprising a proband child or adolescent with ADHD or a typically developing child or adolescent were included and all family members (both biological parents, the proband child or adolescent and their sibling) were examined through semi-structured interviews using DSM-IV criteria. Results indicated that: (a) maternal clinical variables (ADHD, anxiety and depression) were more correlated with offspring variables than paternal ones; (b) maternal inattention (but not hyperactivity) was correlated with both inattention and hyperactivity in the offspring; (c) maternal anxiety was correlated with offspring inattention; on the other hand, maternal inattention was correlated with anxiety in the offspring. Although a family study design limits the possibility of revealing causality and cannot disentangle genetic and environmental factors, our findings suggest that ADHD, anxiety and depression are variables that correlate in families and should be addressed together. Maternal variables significantly correlated with offspring variables, but the paternal variables did not.

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This research was supported by Shire.

Conflict of interest

No ethical issues are foreseen. Daniel Segenreich received speaker’s fees from Janssen-Cilag, Novartis, and Shire in previous years, acted as consultant for Novartis and Shire, and received travel awards to participate in scientific meetings by those companies. Marina S. Paez received research support from Brazilian Council on Research (CNPq). Paulo Mattos was on the speakers’ bureau and/or acted as consultant for Eli-Lilly, Janssen-Cilag, Novartis, and Shire in the previous years; he received travel awards to participate in scientific meetings from those companies. The ADHD outpatient program (Grupo de Estudos do Déficit de Atenção/Institute of Psychiatry) chaired by Dr. Mattos has also received research support from Novartis and Shire. Joseph A. Sergeant has served on the advisory boards of Lilly and Shire, and received grants from Lilly. He has also received speaker’s fees from Shire, Lilly, Janssen-Cillag, and Novartis. Stephen V. Faraone received consulting income, travel expenses and/or research support from Akili Interactive Labs, Alcobra, VAYA Pharma and SynapDx and research support from the National Institutes of Health (NIH). His institution is seeking a patent for the use of sodium–hydrogen exchange inhibitors in the treatment of ADHD. In previous years, he received consulting fees or was on Advisory Boards or participated in continuing medical education programs sponsored by: Shire, Alcobra, Otsuka, McNeil, Janssen, Novartis, Pfizer and Eli-Lilly. Other authors have no conflict of interests.

Ethical Standards

Both local and national medical ethics committees approved the research project in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from all participants prior to their inclusion in the study, and all data regarding participating children was obtained with the permission of their parents.

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Segenreich, D., Paez, M.S., Regalla, M.A. et al. Multilevel analysis of ADHD, anxiety and depression symptoms aggregation in families. Eur Child Adolesc Psychiatry 24, 525–536 (2015).

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  • Attention-deficit disorder
  • ADHD
  • Genetic epidemiology
  • Multilevel analyses