27 July 2012. The clinical demarcations among autism, schizophrenia, and bipolar disorder are not set in stone, and a new study suggests they have shared roots. Published online July 2 in Archives of General Psychiatry, the study finds that having a first-degree relative with schizophrenia or bipolar disorder increased risk for autism in three separate samples, with odds ratios ranging from 1.5 to 12.
Led by Patrick Sullivan of the University of North Carolina in Chapel Hill, the study echoes and extends an earlier Danish study that found having a parent with schizophrenia was a significant risk factor for autism (Larsson et al., 2005). The findings hint at common causes behind the disorders—an idea consistent with recent genomic findings in which certain rare copy number variants (CNVs) boost risk for both autism and schizophrenia (e.g., 3q29, 15q13.3, 16p11.2) (see SRF related news story and SRF news story; Malhotra and Sebat, 2012). Given emerging evidence for common etiology between schizophrenia and bipolar disorder (ISC, 2009), the new study also considers a family history of bipolar disorder. Whether such shared risk factors—genetic or environmental—can produce distinct clinical outcomes, or whether they call attention to phenotypic commonalities between these disorders (e.g., autism was once considered childhood schizophrenia) remains unclear.
Swedish and Israeli samples
First author Sullivan and colleagues in Sweden and Israel evaluated the family histories of people with autism identified in three samples: 25,432 cases from the National Patient Register in Sweden, 4,982 cases culled from ASD treatment center records in Stockholm County in Sweden, and 386 cases from conscript records in Israel, which contain medical and psychiatric assessments to determine a person’s eligibility for mandatory military service. For comparison, for each autism case the researchers identified 10 controls matched for sex, age, birth year, and sex of relatives in the Swedish samples; in the Israeli sample, the researchers looked at groups of two or more siblings who did not have an autism diagnosis.
The researchers found an association between autism and a family history of schizophrenia or bipolar disorder. For example, in the Swedish national sample, having a parent or sibling with schizophrenia increased the odds of autism, giving an odds ratio (OR) of 2.9 in the case of a parent, and 2.6 in the case of a sibling. Similarly, having a parent or sibling with bipolar disorder resulted in ORs of 1.9 and 2.5, respectively. The Stockholm County sample results were similar, though they tracked only parent history: having a parent with schizophrenia or bipolar disorder yielded ORs of 2.9 and 1.6, respectively.
Within the Israeli sample, the researchers focused on whether having a sibling with schizophrenia was a risk factor for autism, and found a whopping increase in risk, with an OR of 12. This was accompanied by large confidence intervals, though, which the researchers surmise reflect the smaller sample size of this group. They also mention that, because these conscript assessments are conducted at 17 years of age, those with a schizophrenia diagnosis likely have an earlier-onset form, which may confer greater risk.
Without mental retardation
Family history seemed associated with the type of autism not accompanied by mental retardation, according to information available in the Stockholm County sample. For autism cases without mental retardation, ORs for a parent with schizophrenia or bipolar disorder were 2.6 and 1.5, respectively—higher than ORs obtained for autism cases with mental retardation, which were 1.6 and 1.1 for parental schizophrenia and bipolar disorder, respectively.
Combined with the previous Danish study, this makes four samples with evidence for family history of schizophrenia or bipolar disorder as a risk factor for autism. This consistency firms up the association, which may encourage researchers to cast a wider net across multiple psychiatric diseases in searching for the explanations of one of these disorders. Such etiological overlap also suggests looking harder at the current clinical definitions of these disorders, which may have more in common than typically appreciated.—Michele Solis.
Sullivan PF, Magnusson C, Reichenberg A, Boman M, Dalman C, Davidson M, Fruchter E, Hultman CM, Lundberg M, Långström N, Weiser M, Svensson AC, Lichtenstein P. Family History of Schizophrenia and Bipolar Disorder as Risk Factors for AutismFamily History of Psychosis as Risk Factor for ASD. Arch Gen Psychiatry. 2012 Jul 2:1-5. Abstract