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ADHD Institute Register

16 Oct 2018

Kuja-Halkola R et al. Mol Psychiatry 2018; Epub ahead of print

Individuals with ADHD are at increased risk of developing a number of comorbid psychiatric disorders, including borderline personality disorder (BPD) (Bernardi et al. 2012). Emotional dysregulation has been shown to play a role in the development of BPD and, more recently, ADHD. Despite this, large-scale family studies on the co-occurrence of ADHD and BPD are lacking. This population-based study aimed to estimate the co-occurrence and familial co-aggregation of clinically diagnosed ADHD and BPD in a Swedish population.

This register-based cohort study included 2,113,902 individuals born in Sweden during 1979–2001,* with individuals linked with their relatives using the Multi-Generation Register and Twin Register. Individuals with ADHD were identified using the Swedish National Patient Register (NPR) and Prescribed Drug Register, while individuals with BPD were identified from the NPR only. Associations were estimated using logistic regression. Co-occurrence within individuals was assessed by analysing the within-individual associations between ADHD and BPD to obtain crude and covariate-adjusted odds ratiosǂ (ORs and aORs, respectively). Co-aggregation within relatives was assessed by estimating the risk of BPD in individuals according to their relative’s ADHD and again obtaining ORs and aORs. ORs were also calculated in the full sibling subsample stratified by sex combinations.

Results from the study demonstrated that:

  • During follow-up, 82,593 (3.9%) and 9,544 (0.5%) individuals were diagnosed with ADHD and BPD, respectively. Males were more commonly diagnosed with ADHD, while females were more likely to be diagnosed with BPD.
  • Individuals with an ADHD diagnosis were at an increased risk of BPD, with an aOR of 19.4 (95% confidence interval [CI] 18.6–20.4).
  • Individuals who had a relative with an ADHD diagnosis were also at increased risk of a BPD diagnosis. Monozygotic twins with ADHD had a lower risk of BPD (aOR 11.2, 95% CI 3.0–42.2) than within individuals, suggesting that factors not shared by family members were likely to influence co-occurrence.
  • At least part of the association between ADHD and BPD was due to genetic factors: full siblings had a significantly lower aOR of 2.8 (95% CI 2.6–3.1) compared with monozygotic twins (p=0.041), whereas half-siblings had a significantly lower aOR compared with full siblings (maternal: aOR 1.4, 95% CI 1.2–1.7; paternal: aOR 1.5, 95% CI 1.3–1.7; p<0.001 for both).
  • In full siblings, females with a sister diagnosed with ADHD were at increased risk of having a BPD diagnosis compared with females who had a brother diagnosed with ADHD (aOR 2.9 [95% CI 2.6–3.4] vs 2.5 [95% CI 2.3–2.8]). Males with a sister diagnosed with ADHD also exhibited increased risk compared with males having a brother with ADHD (aOR 3.9 [95% CI 2.9–5.4] vs 3.6 [95% CI 2.7–4.8]). However, neither of these differences were statistically significant (females, p=0.087; males, p=0.682). These findings do not support the presence of aetiological sex differences.

This is the largest study of ADHD and BPD co-occurrence and, to the authors’ knowledge, the only study to date that has evaluated the familial co-aggregation of clinically diagnosed ADHD and BPD. Despite this, the study was limited by a number of factors that could have led to potential sources of bias. First, the diagnoses observed in the study are likely under-reported, which could have biased results towards the null. Second, correlated detection bias may have been present in individuals with one diagnosis, which could have biased estimates upwards. Additionally, misdiagnosis may have occurred due to an overlap in symptoms between ADHD and BPD, leading to a spurious association between the two disorders.

The authors concluded by stating that ADHD and BPD co-occur in individuals, and also co-aggregate in relatives; this pattern reflects both shared genetic risk factors and individually unique risk factors. Furthermore, the strength of individual and familial associations between ADHD and BPD was similar across sexes, suggesting that the presence of aetiological sex differences was not robustly supported. The authors stated that these findings are important to promote awareness of the increased risk of BPD in individuals with ADHD, as well as their relatives, and vice versa.

Learn more about the co-occurrence and familial co-aggregation of BPD and ADHD here

 

*Exclusion criteria included stillbirths, congenital malformations, and deaths during infancy (total of 108,079). Individuals who died (6283) or emigrated (72,337) before their 12th birthday were excluded using the Cause of Death Register and the Total Population Register, respectively. Individuals who did not have both parents known (19,093) were also excluded using the Multi-Generation Register
The NPR comprises diagnoses from inpatient healthcare, and from outpatient visits to specialist care from 2001 and onwards; the authors used International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) diagnoses from 1 January 1997 (when the ICD-10 was introduced in Sweden) to 31 December 2013. The authors used data from PDR on all dispensed medications from 1 June 2005 to 31 December 2014
ǂCovariates included sex, birth year and birth order, as they are potential confounders associated with both ADHD and BPD. Adjusted ORs were adjusted for sex, sex of relative, birth year, birth year of relative and birth order, wherever applicable

Bernardi S, Faraone SV, Cortese S, et al. The lifetime impact of attention-deficit hyperactivity disorder: results from the National Epidemiologic Survey of Alcohol and Related Conditions. Psychol Med 2012; 42: 875-887.

Kuja-Halkola R, Lind Juto K, Skoglund C, et al. Do borderline personality disorder and attention-deficit/hyperactivity disorder co-aggregate in families? A population-based study of 2 million Swedes. Mol Psychiatry 2018; Epub ahead of print.

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