Schizophrenia, autism may be linked in families

Families with a history of schizophrenia or bipolar disorder are also more likely to have a child with autism, new research from Sweden and Israel suggests.

Researchers found that kids whose parents or siblings had been diagnosed with schizophrenia were almost three times more likely to have an autism spectrum disorder, including autism and Asperger syndrome.

The link was weaker for bipolar disorder, but still consistent, according to findings published this week in the Archives of General Psychiatry.

“Most people with a family history of one of these disorders actually get nothing - the vast majority in fact,” said Dr. Patrick Sullivan, the study’s lead author from the University of North Carolina at Chapel Hill.

Still, he told Reuters Health, “Maybe there is something that is more fundamental but common to both,” such as certain changes in gene patterns that are passed from parents to children.

The number of autism diagnoses in the United States has been rising, and the Centers for Disease Control and Prevention now estimates one in 88 kids has an autism spectrum disorder. That’s up from one in 150 a decade ago.

One of the questions in recent autism research has been how much genetics is involved in who gets the condition, versus the prenatal or early childhood environment.

Sullivan and his colleagues note that autism used to be considered the childhood version of schizophrenia, before researchers learned more about the two disorders. And some research has continued to suggest certain genetic changes are common in both conditions, as well as in bipolar disorder.

So for the new study, the researchers analyzed information from three separate databases, including two that tracked kids and families in Sweden and their medical diagnoses and a third that recorded data on all Israeli citizens entering the army draft, including sibling pairs.

All in all, Sullivan’s team had data on more than 30,000 young people with autism.

The researchers found that in the Swedish studies, kids whose parent or sibling had been diagnosed with schizophrenia, according to family medical records, were 2.6 to 2.9 times more likely to have autism. The trend was the same for siblings of teens with schizophrenia in Israel.

When a parent had bipolar disorder, on the other hand, kids were 1.6 to 1.9 times more likely to have autism or another autism spectrum disorder.

“It’s been questioned for many years, whether there’s a relationship” between schizophrenia and autism, said Dr. Andrew Zimmerman, a neurologist from the Lurie Center for Autism at MassGeneral Hospital for Children in Lexington, Massachusetts.

“In fact, I think those of us that see a lot of patients with autism have seen this relationship in relatives for a long time,” he added.

Sullivan said there are certain rare genetic mutations that seem to predispose people to both autism and schizophrenia.

And there could be other gene variations, he said, where differences in a person’s environment in the womb or growing up could influence whether the same mutation ends up leading to schizophrenia, autism or nothing.

“Just because two things share a risk factor doesn’t mean that they’re the same thing,” Sullivan added. “The needs of people with autism and schizophrenia, and the treatments that we know work for one or the other, don’t overlap very well.”

Zimmerman, who wasn’t involved in the current research, told Reuters Health there are still many questions about how the conditions may be related.

The new study “is important because it makes us think,” he said. “It doesn’t tell us whether (autism and schizophrenia) are genetic or environmental - certainly both are still possible - but it makes us think there might be relationships between the two.”

SOURCE: Archives of General Psychiatry, online July 2, 2012

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Family History of Schizophrenia and Bipolar Disorder as Risk Factors for Autism

Conclusions  Findings from these 3 registers along with consistent findings from a similar study in Denmark suggest that ASD, schizophrenia, and bipolar disorder share common etiologic factors.

Autism spectrum disorders (ASDs) and schizophrenia are currently considered as distinctive and infrequently overlapping. Historically, ASD was often regarded as childhood schizophrenia because the impaired social interactions and bizarre behavior found in ASD were reminiscent of symptoms of schizophrenia. Indeed, the psychiatrist who coined the term schizophrenia counted autism (an active turning away from the external world) as an important distinguishing feature of schizophrenia. Around 1980, the nosologic status of ASD and schizophrenia was revised so that these disorders were separated. The separation was strongly influenced by developmental trajectory and delineated infantile autism present from very early in life from schizophrenia where psychotic symptoms developed after an extended period of normal or near-normal development.

Several lines of evidence suggest that this distinction is not absolute, and that there are important overlaps between ASD and schizophrenia. Some family history studies (although not all) found that the relatives of probands with ASD were more likely to have a history of schizophrenia. However, these studies tended to be small and relatively underpowered. Childhood-onset schizophrenia is a rare subtype, and a sizable fraction have premorbid ASD. More directly, genomewide copy number variation studies have identified rare mutations that are strong risk factors for both ASD and schizophrenia (eg, 15q13.3, 16p11.2, 22q11.21, and in neurexin 1). These points of overlap are quite uncommon, and they apply to only a fraction of clinical samples.

The degree to which ASD and schizophrenia share etiologic factors has important implications for clinicians, researchers, and those affected by these diseases. Therefore, we investigated whether a family history of schizophrenia and/or bipolar disorder in first-degree relatives was a risk factor for ASD. Bipolar disorder was included given its etiologic and clinical overlap with schizophrenia. We conducted parallel analyses in 3 samples to evaluate the consistency and generalizability of the findings.


Patrick F. Sullivan, MD, FRANZCP; Cecilia Magnusson, MD, PhD; Abraham Reichenberg, PhD; Marcus Boman, BS; Christina Dalman, MD, PhD; Michael Davidson, MD; Eyal Fruchter, MD; Christina M. Hultman, PhD; Michael Lundberg, MPH; Niklas Långström, MD, PhD; Mark Weiser, MD; Anna C. Svensson, PhD; Paul Lichtenstein, PhD

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