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23 Mar 2017

Chen Q et al. J Child Psychol Psychiatry 2017; 58: 231-239

There is clear evidence that ADHD aggregates in families; however, population-based family samples are required to assess the strength, pattern and characteristics of this observation.

In this patient-cohort study, 1,656,943 unique individuals born between 1 January 1985 and 31 December 2006 were identified from the Swedish Twin Register from relative pairs of twins, full and half-siblings, and full and half cousins. The relatives of these individuals were followed from their third birthday until first ADHD diagnosis* or 31 December 2009, whichever occurred first. Analysis of the results took into account a number of covariates that might explain the familial aggregation of ADHD, including birth year (1985–1991, 1992–1996, 1997–2001, 2002–2006), gender, maternal age at childbirth (<35 and ≥35 years), paternal age at childbirth (<45 and ≥45 years) and presence of maternal and paternal psychiatric history.

ADHD was diagnosed during follow-up in 31,865 individuals (male:female ratio was 3.7), generating a lifetime prevalence of 1.9%. Cumulative incidence of ADHD diagnosis at age 20 for both siblings and cousins of unaffected individuals was ~3.6%, compared with 25.3% and 10.0%, respectively, for siblings and cousins of ADHD-affected individuals.

Familial aggregation of ADHD was measured using crude and birth-year–adjusted hazard ratios (HRs) for ADHD diagnosis, with the estimates being 70.45 (95% confidence interval [CI] 38.19–129.96) in monozygotic twins, 8.44 (95% CI 5.87–12.14) in dizygotic twins, 8.27 (95% CI 7.86–8.70) in full siblings, 2.86 (95% CI 2.61–3.13) in maternal half-siblings, 2.31 (95% CI 2.07–2.58) in paternal half-siblings, 2.24 (95% CI 2.11–2.38) in full cousins and 1.47 (95% CI 1.35–1.61) in half cousins. The HR in maternal half-siblings was significantly higher than in paternal half-siblings (p=0.004).

Further analysis indicated that the HR did not seem to be affected by gender. Compared with siblings of individuals without ADHD, male and female siblings of individuals with ADHD had a ~8- and 10-fold increase in the rate of ADHD diagnosis, respectively. Full siblings of individuals with an ADHD diagnosis present at age ≥18 years had a higher rate of ADHD (HR 11.49) compared with full siblings of individuals with an ADHD diagnosis prior to age 18 years (HR 4.68). Analysis of results by parental age and parental psychiatric history did not affect the magnitude of the HRs.

Study limitations included a lower lifetime prevalence of ADHD in this study compared with other countries, and that paternity tests for excluding paternal discrepancy were not available.

In conclusion, this study indicates that familial aggregation of ADHD increases with increasing genetic relatedness. It is also important to note that familial aggregation is driven by not only genetic factors but also by a small amount of shared environmental factors, and that persistence of ADHD into adulthood appears to index stronger familial aggregation of ADHD.

Read more about familial aggregation of ADHD here

 

*Date of first ADHD diagnosis (International Statistical Classification of Diseases and Related Health Problems, 9th Revision [ICD-9], ICD-10 or Diagnostic and Statistical Manual of Mental Disorders – 4th edition) was defined as the date of the first registered diagnosis or drug prescription (methylphenidate, amfetamine, dexamfetamine or atomoxetine), whichever occurred first
Psychiatric history was defined as the presence of any psychiatric diagnosis (ICD-8: 290–315; ICD-9: 290–319; ICD-10: F00–F99) before the birth of the first-born child in a nuclear family during the study period

Chen Q, Brikell I, Lichtenstein P, et al. Familial aggregation of attention-deficit/hyperactivity disorder. J Child Psychol Psychiatry 2017; 58: 231-239.

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