Genetic analysis predicts autism or psychosis in children born with chromosomal disorder

By John Murphy, MDLinx
Published January 5, 2016

Key Takeaways

New research has found a way to genetically determine which children with a specific chromosomal disorder may have autism and which may have psychosis, according to a study published in PLoS ONE.

Scientists have surmised that autism spectrum disorders (ASD) and psychotic illness have distinctly different phenotypes. Yet there has been no way to predict which child might be at risk for which disorder. New findings by researchers at University of California Los Angeles (UCLA) and the University of Pittsburgh are the first to suggest a way to predict between the two.

“Ultimately, this kind of information could be used as a diagnostic tool that could allow pediatricians or other clinicians to determine who will develop which disorder, so that the appropriate intervention can be applied—and applied early enough to have the most impact,” said senior author Carrie Bearden, PhD, professor of psychiatry and psychology at UCLA. “We know that early intervention is very important for people at risk for autism or psychosis.” 

The research focused on children with 22q11.2 deletion syndrome (22q11DS), also known as DiGeorge syndrome, which is the second most common genetic abnormality after Down syndrome. This syndrome represents one of the greatest known genetic risk factors for the development of psychotic illness and is also associated with high rates of ASD in childhood—between 25% and 30% of individuals with the syndrome are diagnosed with a psychotic disorder and 30% to 40% are diagnosed with a disorder on the autism spectrum. A small number are diagnosed with both autism and psychosis.

22q11.2 deletion syndrome affects roughly 1 in 2,500 children born worldwide, and can be detected with an amniocentesis. Children born with this syndrome often have elongated faces, almond-shaped eyes, and unusual outer ears. They frequently have palate abnormalities, including cleft palate, and they are at elevated risk for cardiovascular defects.

In this study, the investigators set out to determine whether ASD and psychosis demonstrated different gene expression patterns in children with this syndrome; however, analyzing the enormous amount of genetic information would have put a strain on available testing methods. Enter a new technique developed at UCLA called weighted gene co-expression network analysis, which allows the researchers to look for patterns of genes that are connected to one another.

To do so, the researchers took blood samples from 46 UCLA patients with 22q11DS and 66 control subjects, then analyzed the samples using weighted gene co-expression network analysis.

“The hope is that eventually we could identify individuals at risk for either disorder with a blood sample,” said lead author Maria Jalbrzikowski, PhD, who is now at the University of Pittsburgh but was a postdoctoral fellow in Dr. Bearden’s lab while they were conducting the study.

Analysis results showed that, on average, people with DiGeorge syndrome and psychosis had 237 genes that showed a different pattern from the genes of people with the syndrome but without psychosis. Most of these genes were associated with the regulation of gene expression. 

Next, the researchers looked at the psychosis-related genes in the DiGeorge syndrome patients with psychosis and compared those against a sample of 180 Dutch patients who had been diagnosed with schizophrenia but did not have the syndrome. They found an overlap of 7 genes.

“This finding is really important because it provides proof that altered gene expression patterns in those with DiGeorge syndrome and psychosis are shared with people who are diagnosed with schizophrenia but do not have the deletion,” Dr. Bearden said. “The same pathways are affected.”

The 7 overlapping genes play a role in fetal brain development, which suggests that psychosis may originate during the early stages of brain development, she said.

Meanwhile, the DiGeorge syndrome patients with autism differed from their counterparts without autism in the expression of 86 genes, which were primarily related to immunological processes and functions. This finding, combined with prior research, suggests that ASD pathology may be related to an innate immune system response to neuronal disturbances, the authors wrote in their study.

In future research, the investigators hope to replicate their findings in larger groups and in other cell types (such as brain tissue) in patients with DiGeorge syndrome.

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