Family History of Mental and Neurological Disorders and Risk of Autism
Authors: Sherlly Xie, Håkan Karlsson, Christina Dalman, Linnea Widman, Dheeraj Rai, Renee M. Gardner, Cecilia Magnusson, Diana E. Schendel, Craig J. Newschaffer, Brian K. Lee
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Familial aggregation of mental and neurological disorders is often observed in autism spectrum disorders (ASD), but reports have generally focused on single disorders and are limited to first-degree relatives. <h3>Objectives</h3> To examine family history of mental and neurological disorders among first- to fourth-degree relatives and risk of ASD with and without intellectual disability (ID) in index persons. <h3>Design, Setting, and Participants</h3> In this population-based cohort study, 567 436 index persons were identified from the Stockholm Youth Cohort, an ongoing longitudinal register-linkage cohort study of the total population aged 0 to 17 years residing in Stockholm County, Sweden. Index persons were nonadopted singleton births born between 1984 and 2009 who were at least 2 years of age at the end of follow-up on December 31, 2011, had resided in Stockholm County for at least 2 years since birth, and could be linked to both biological parents. Data analysis was conducted from May 2017 to December 2018. <h3>Exposure</h3> Mental and neurological diagnoses of relatives of the index persons. <h3>Main Outcomes and Measures</h3> Diagnosis of ASD, with or without co-occurring ID, in the index persons. <h3>Results</h3> The cohort included 567 436 index persons (291 191 [51.3%] male; mean [SD] age at the end of follow-up, 14.3 [7.5] years). The prevalence of ASD with and without ID was 0.4% and 1.5%, respectively. Positive family history of mental and neurological disorders was associated with higher odds of ASD in index persons; 6895 (63.1%) of index persons with ASD had a parent with history of mental and/or neurological disorders, compared with 252 454 (45.4%) of index persons without ASD. Family history of multiple disorders was associated with higher odds of ASD in index persons, including history of ASD (odds ratio among first-degree relatives for ASD with and without ID: 14.2, 9.0), intellectual disability (7.6, 2.3), attention-deficit/hyperactivity disorder (3.3, 4.7), obsessive compulsive disorder (1.9, 2.1), schizophrenia and other nonaffective psychotic disorders (2.1, 1.8), depression (1.4, 2.0), bipolar disorder (1.4, 2.2), personality disorder (2.1, 2.6), cerebral palsy (2.2, 1.5), and epilepsy (2.0, 1.3). The more closely related the affected family member was, the higher the odds was of ASD for the index person. ASD without intellectual disability was associated with more disorders compared to ASD with intellectual disability. ASD with intellectual disability exhibited a weaker familial association with other mental disorder diagnoses but a stronger familial association with some neurological diagnoses as compared to ASD without intellectual disability. <h3>Conclusions and Relevance</h3> This study suggests that family history of mental and neurological disorders is associated with increased risk of ASD. The familial component of ASD etiology may differ by presence or absence of co-occurring ID.