- Note that in this study, the presence of schizophrenia in parents was associated with an increased risk for autism spectrum disorders and, similarly, schizophrenia in a sibling was associated with an increased risk for autism spectrum disorders.
- Point out that the findings in this study suggest that autism spectrum disorders, schizophrenia, and possibly bipolar disorder share common etiologic factors.
Study Links Autism, Bipolar, and Schizophrenia
Study Links Autism, Bipolar, and Schizophrenia
Autism spectrum disorder appears more likely for children with schizophrenia or bipolar disorder in their immediate family, suggesting common factors among the three, researchers found.
The autism risk was 2.9-fold higher with schizophrenia in parents and 2.6- to 12.1-fold elevated with schizophrenia in a sibling across various cohorts studied by Patrick F. Sullivan, MD, of the University of North Carolina at Chapel Hill, and colleagues.
The links were similar but lesser in magnitude for bipolar disorder in a first-degree family member, the group reported online in theArchives of General Psychiatry.
The findings suggest that schizophrenia, bipolar disorder, and autism are different manifestations of the same root causes.
The common factors could be shared DNA sequence variation, a common environmental risk factor the whole family is exposed to, or a gene-environment interaction, Sullivan and colleagues suggested.
"Genetic effects may be more likely given substantial heritability estimates for autism spectrum disorder, schizophrenia, and bipolar disorder along with evidence for relatively lesser but significant environmental effects," they wrote.
But that doesn't necessarily mean that all three should be lumped together into a single psychiatric classification just yet, the group pointed out.
Rather, "it is tenable that these disorders are more similar phenotypically than currently appreciated, and it might prove interesting to reevaluate the degrees of demarcation between these three disorders," Sullivan's group wrote.
Bipolar disorder has a well known etiologic and clinical overlap with schizophrenia.
Autism used to be "regarded as childhood schizophrenia because the impaired social interactions and bizarre behavior found in autism spectrum disorder were reminiscent of symptoms of schizophrenia," the researchers noted.
While the two were separated diagnostically around 1980, they explained, "several lines of evidence suggest that this distinction is not absolute."
The group examined histories of schizophrenia or bipolar disorder in first-degree relatives of individuals with autism spectrum disorder in three cohorts:
- The national inpatient and outpatient registries in Sweden dating back to 1973, which included 25,432 autism spectrum disorder cases, each matched to 10 controls for sex, birth year, and sex of relatives
- A registry of primarily outpatient facilities for treating autism in the Stockholm area, with 4,982 cases and 49,844 controls from 1984 through 2007
- A database of standardized psychiatric assessment of conscripts for compulsory military service in Israel, which included 386 cases born in the 1980s and 436,311 controls
The link between autism spectrum disorder and family history of the other psychiatric disorders was consistently significant across the cohorts and categories studied.
The likelihood of autism spectrum disorder was 2.9-fold elevated with a parental history of schizophrenia in both the Swedish national cohort (95% confidence interval 2.5 to 3.4) and the Stockholm County cohort (95% CI 2.0 to 4.1).
Schizophrenia in a sibling raised the risk 2.6-fold in the Swedish national cohort and 12.1-fold in the Israeli conscription cohort, though with a larger 95% confidence interval of 4.5 to 32.0 that overlapped with the confidence interval of 2.0 to 3.2 in the national cohort.
"We speculate that the higher sibling odds ratio from Israel resulted from subjects with earlier onset schizophrenia, which has a higher sibling recurrence risk," Sullivan's group wrote.
Bipolar disorder in a parent was associated with:
- 90% elevated odds of autism spectrum disorder in the Swedish national cohort (95% CI 1.7 to 2.1)
- 60% elevated odds of autism spectrum disorder in the Stockholm cohort (95% CI 1.1 to 2.1)
The associations appeared stronger in autism spectrum disorder without a clinical indication of mental retardation but didn't vary by sex of either the relative or the autism case.
The Stockholm cohort didn't have sibling data available, while the Israeli cohort didn't have data on family history of bipolar disorder.
Another potential limitation of the Swedish national cohort was that it started collecting outpatient data only in 2001 and couldn't be used for prevalence estimates because it was not yet complete.
But variations in reporting from different healthcare providers were deemed unlikely to be correlated with family history of psychotic symptoms by the researchers.
The study was funded by the Swedish Council for Working Life and Social Research, the Swedish Research Council, and the Beatrice and Samuel A. Seaver Foundation.
The researchers reported having no conflicts of interest to disclose.
Primary source: Archives of General Psychiatry
Sullivan PF, et al "Family history of schizophrenia and bipolar disorder as risk factors for autism" Arch Gen Psychiatry 2012; DOI: 10.1001/archgenpsychiatry.2012.730.