The risk of siblings of individuals with ADHD developing psychiatric and neurodevelopmental disorders has not been thoroughly assessed in a population-based cohort. Previously, only two studies which examined disorders beyond ADHD in siblings have been conducted. These studies showed a nearly two-fold increase in the risk of substance abuse and schizophrenia, and more than a two-fold risk for bipolar disorder. However, these studies looked mainly at disorders diagnosed in adulthood only, and did not consider childhood-onset conditions. This information could provide valuable insight regarding at-risk individuals among the siblings of individuals diagnosed with ADHD. This study aimed to examine a wide range of different psychiatric and neurodevelopmental disorders in siblings of children diagnosed with ADHD. Additionally, the study also examined these associations when stratified by gender, to investigate the concept of the ‘female protective model’, which suggests that greater levels of exposure to risk factors are required for females to develop neurodevelopmental disorders such as ADHD than males.
This study formed part of a Finnish nationwide ADHD register study, and used data from three registers.* Use of these registers allowed identification of every child born in Finland between 1991 and 2005 (N=900,603), and diagnosed with ADHD† between 1995 and 2011. Each child with ADHD was individually matched with four controls on gender, date of birth (±30 days) and place of birth. Full siblings of cases and controls born between 1981 and 2007 were included in the analysis, and any psychiatric and neurodevelopmental diagnoses‡ up to the end of 2013 were determined from the Finnish Hospital Discharge Register (FHDR). Cases and controls without full siblings were excluded from the analysis. This approach yielded data from 7369 cases with 12,565 full siblings and 23,181 controls with 42,753 full siblings. Analysis was performed using generalised estimating equations.
The results of this study showed that:
- Compared with controls, more individuals with ADHD had ≥1 sibling diagnosed with any psychiatric or neurodevelopmental disorder (44.2% vs 22.2%; risk ratio [RR] 2.1; 95% confidence interval [CI] 2.0–2.2; p<0.001).
- The risk for childhood-onset disorders was greater in siblings of individuals with ADHD compared with controls (36.7% vs 15.3%; RR 2.5; 95% CI 2.4–2.6; p<0.001).
- An increased risk among the siblings of individuals with ADHD was demonstrated for all disorders examined except eating disorders.
- The strongest risks were observed for ADHD (RR 5.7; 95% CI 5.1–6.3; p<0.001), conduct and oppositional disorders (RR 4.0; 95% CI 3.5–4.5; p<0.001) and autism spectrum disorder (RR 3.9; 95% CI 3.3–4.6; p<0.001).
- Greater than two-fold increased risks were demonstrated for other emotional and social interaction disorders (RR 2.7, 95% CI 2.4–3.1; p<0.001), learning and co-ordination disorders (RR 2.6; 95% CI 2.4–2.8; p<0.001), tic disorders (RR 2.5; 95% CI 1.9–3.3; p<0.001) and intellectual disability (RR 2.4; 95% CI 2.0–2.8; p<0.001).
- Siblings of the individuals with ADHD were also at an increased risk for bipolar disorder (RR 1.9; 95% CI 1.4–2.6; p<0.001), unipolar mood disorders (RR 1.9; 95% CI 1.7–2.0; p<0.001), schizophrenia spectrum disorders (RR 1.8; 95% CI 1.5–2.3; p<0.001), other neurotic and personality disorders (RR 1.7; 95% CI 1.4–2.0; p<0.001), substance-use disorders (RR 1.7; 95% CI 1.5–2.0; p<0.001) and anxiety disorders (RR 1.4; 95% CI 1.3–1.6; p<0.001).
- Stratifying the data by gender (of the individual with ADHD), an interaction analysis showed that siblings of female individuals with ADHD were at greater risk of any psychiatric or neurodevelopmental disorder (p=0.03), any childhood-onset disorder (p=0.02), intellectual disability (p=0.01), and learning and co-ordination disorders (p<0.01).
There were several limitations to this study. Firstly, no verification of the psychiatric disorders reported in the FHDR was performed, although conditions such as ADHD, autism spectrum disorder, tic disorders, schizophrenia and bipolar disorder have all been shown to have good validity in this register. Additionally, the FHDR only reports individuals diagnosed in specialised services and not primary healthcare, which could lead to an underestimation of less severe conditions where treatment occurs in the primary healthcare setting. However, the authors indicated that coverage of moderate and severe conditions in this study is expected to be good, due to the universal and state-funded nature of the Finnish healthcare system. Finally, the fact that treatment-seeking behaviours could vary for siblings of individuals with and without ADHD could be an additional limitation. However, given the routine yearly assessment carried out in children up to the age of 7 in Finland, during which concerns regarding neurodevelopmental disorders would trigger referral to specialised healthcare, this seems unlikely.
The authors concluded that this study has shown that the risks of different psychiatric and neurodevelopmental disorders are elevated in siblings of children with ADHD, suggesting shared familial and environmental vulnerability factors. The authors suggested that these results may aid the identification of at-risk siblings, and that further studies on common aetiologies are required. Although the data presented fit with the ‘female protective model’, further investigation is required before any conclusions can be drawn.
*The Finnish Central Population Register, the Finnish Hospital Discharge Register and the Finnish Medical Birth Register
†Diagnosis of ADHD, as identified from the FHDR, was based on the International Statistical Classification of Diseases and Related Health Problems Ninth Revision (ICD-9) and Tenth Revision (ICD-10). The most recent diagnosis was used, such that all cases were diagnosed with ADHD according to the ICD-10
‡Diagnoses of any psychiatric or neurodevelopmental disorders, as identified from the FHDR, were based on the ICD-8 from 1969 to 1986, the ICD-9 from 1987 to 1995 and the ICD-10 from 1996 onwards. Pooled diagnostic classes including ‘psychiatric/neurodevelopmental disorder’ and ‘any disorder usually diagnosed in childhood’ were classified using a dichotomous variable (i.e. yes/no). For multiple disorders in siblings (e.g. anxiety and eating disorder), the sibling was considered positive for all of them
Jokiranta-Olkoniemi E, Cheslack-Postova K, Joelsson P, et al. Attention-deficit/hyperactivity disorder and risk for psychiatric and neurodevelopmental disorders in siblings. Psychol Med 2019; 49: 84-91.