Family History of Mental Disorders Linked to Autism Spectrum Disorder Risk

Autism spectrum disorders with and without intellectual disability showed different patterns of association with familial mental and neurological disorders.

History of mental and neurological disorders in first-to-fourth degree family members is associated with an increased risk for autism spectrum disorder (ASD), according to study results published in JAMA Network Open.

The study cohort included 567,436 index persons, 51.3% of whom were male. The mean age of all participants at the end of follow-up was 14.3 years. The prevalence of ASD with intellectual disability (ASD-ID; n=2566) and without ID (ASD-No ID; n=8354) was 0.4% and 1.5%, respectively.

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Higher odds of ASD in index persons was linked to positive family history of mental and neurological disorders. Of the participants, 6895 (63.1%) index persons (IPs) with ASD (ASD-ID) had a parent with history of mental and/or neurological disorders, compared with 252,454 (45.4%) of IPs without ASD (ASD-No ID). Specifically, family history of ASD was associated with higher odds of ASD in IPs. The odds ratio (OR) for having first-degree relatives with ASD-No ID was 4.1 for IPs with ASD-ID and 9.0 for IPs with ASD-No ID. For having first-degree relatives with ASD-ID, the ORs were 14. 2 for IPs with ASD-ID and 3.8 for IPs with ASD-No ID.

Other mental disorders diagnosed in relatives that had high ORs were ID (ASD-ID, 7.6 vs ASD-No ID, 2.3), attention-deficit/hyperactivity disorder (ASD-ID, 3.3 vs ASD-No ID, 4.7), schizophrenia and other nonaffective psychotic disorders (ASD-ID, 2.1 vs ASD-No ID, 1.8), depression (ASD-ID, 1.4 vs ASD-No ID, 2.0), bipolar disorder (ASD-ID, 1.4 vs ASD-No ID, 2.2), and personality disorder (ASD-ID, 2.1 vs ASD-No ID, 2.6); neurological disorders with high ORs included cerebral palsy (ASD-ID, 2.2 vs ASD-No ID, 1.5) and epilepsy (ASD-ID, 2.0 vs ASD-No ID, 1.3).

The more closely related an affected family member was, the higher the odds of an ASD diagnosis for the IP. Although a history of ASD-No ID, attention-deficit/hyperactivity disorder, other childhood disorders, or anxiety disorders in fourth-degree relatives remained significantly associated with higher odds of ASD-ID in IPs, ASD-No ID was associated with more mental health disorders in general, whereas ASD-ID exhibited a stronger familial association with some neurological diagnoses.

The odds of ASD-No ID in IPs increased by 1.5-, 1.3-, and 1.3-fold when a first-degree relative had cerebral palsy, epilepsy, or migraine, respectively. The association was decreased with a decreasing degree of relatedness between the IP and relatives.

Researchers did not adjust for comorbidity and family history, and were not able to obtain data on all possible disorders relevant to the familiar risk.

“This study suggests that family history of mental and neurological disorders is associated with autism risk, and the familial component of autism etiology may differ by presence or absence of co-occurring intellectual disability,” the researchers concluded.

Disclosures: Multiple authors declared disclosures. Please refer to reference for a complete list of authors’ disclosures.


Xie S, Karlsson H, Dalman C, et al. Family history of mental and neurological disorders and risk of autism. JAMA Netw Open. 2019;2(3):e190154.

This article originally appeared on Psychiatry Advisor