Psychiatric Disorders in Parents and Siblings of Individuals Diagnosed with Autism Spectrum Disorders in a Danish Historic Birth Cohort: A Register-Based Follow-up Study

Background:

The neurobiological basis of autism spectrum disorders (ASD) is complex and several lines of research suggest that both genetic and environmental factors contribute etiologically to the disease. While several studies have reported higher prevalence of co-existing psychiatric disorders in individuals with ASD, studies examining prevalence of psychiatric disorders in parents and siblings of individuals with ASD are rather limited.

Objectives:

The aim of this study is to estimate the psychiatric disorders ratios in parents and siblings of individuals diagnosed with ASD and their frequency-matched controls utilizing a Danish Historic Birth Cohort (HBC).

Methods:

Danish nation-wide health registers were utilized to identify individuals diagnosed with ASD and their controls in the HBC. All singleton ASD cases born between 1982 and 2000 in the HBC were identified based on ICD-8 codes 299.xx up to 1993, and ICD-10 codes DF84.xx since 1994. Controls were non-ASD singleton individuals in the HBC frequency-matched with cases on gender and year of birth. Danish nation-wide administrative and health registers were utilized to identify and follow-up parents and siblings of individuals diagnosed with ASD and their controls in the HBC for psychiatric diagnoses until September 1^st, 2009. Psychiatric diagnoses were identified utilizing the Danish Psychiatric Central Register complemented with data from the Danish national hospital register. The prevalence of psychiatric disorders among parents and siblings of individuals with ASD and controls were determined. Case-control comparisons were performed using Mantel–Haenszel Chi square tests and Mantel–Haenszel estimate of the odds ratio (OR) controlling for gender and year of birth.

Results:

The study population consisted of 414 ASD cases and 820 controls. Maternal and paternal data were available for more than 97% of cases and controls. Siblings were identified relying on maternal and paternal data. After excluding twins, siblings were classified into same parents-siblings, paternal-side siblings and maternal-side siblings.  On aggregate level, register-based psychiatric disorders were significantly more prevalent in parents and siblings of ASD patients compared to controls. Fathers of ASD patients were at increased risk of being diagnosed with psychiatric disorder compared to fathers of controls (OR 1.54 with confidence interval [CI] [1.06 – 2.25]) and this was comparable in mothers as well (OR 1.51 CI [1.10 – 2.09]). Estimates were mainly driven by mood (affective) disorders (DF30.0 – DF39.0). Among siblings of ASD patients, prevalence of ASD averaged 2.9% compared to 0.8% among siblings of controls (OR 3.46 CI [1.33 – 8.98]). Comparable to parents, siblings of ASD patients had increased risk of being diagnosed with psychiatric disorder compared to siblings of controls (OR 2.04 CI [1.59 – 2.62]) and this was most significant in same parents-siblings.

Conclusions:

Findings in this study suggest increased prevalence of psychiatric disorders in parents and siblings of individuals with ASD compared to controls. While this study had number of limitations such as a potential cohort effect and reliance on national registers rather symptomatology information, associations reported should be considered not only on a molecular level in the context of a hybrid genetic/environmental ASD etiopathology but also from a mental health policy perspective.