Early psychosis may be genetic

Illustration of a family searching for answers to their children's early psychosis, with genes and frightening images
Psychotic symptoms in children may be misdiagnosed, ignored as a normal developmental stage, or attributed to stress. New work has found that early psychosis can have a genetic cause. (Images: Adobe Stock. Illustration: David Crissom, Boston Children’s Hospital)

A 6-year-old boy started seeing ghosts and aliens on trees and colorful footprints. Most disturbingly, he heard noises coming from the walls and the school intercom telling him to harm himself and others. Joseph Gonzalez HydeRich, MDThe psychiatrist at Boston Children’s Hospital, put him on antipsychotic medication at the age of nine. The frightening hallucinations stopped.

While children are known for their active imagination, it is very rare for them to develop true psychotic symptoms. Concerned, Gonzalez Heydrich arranged for the boy to undergo a genetic test. One test, known as chromosomal microarray analysis, He found that he had lost a piece of his DNA: He had only one copy of chromosome region 16p13.11 when he should have had two copies.

Another kid, four years old, was having hallucinations with monsters, a big black wolf, spiders, and a man with blood on his face. He was found to have a duplicate piece of DNA.

Today d. Gonzalez Heydrich and his colleague David Gallan, Ph.D.and they formed Early Psychosis Investigation Center (EPICenter) at Boston Children’s to better understand these rare cases. In a study just published in American Journal of PsychiatryNow they have genetically tested 137 children and teens with what’s known as early psychosis, or psychotic symptoms that develop before the age of 18.

The findings open a path toward diagnosing and caring for these devastating conditions, helping traumatized families recover, and possibly accelerating the development of better antipsychotic drugs.

The genetics of early psychosis: copy number variants

More than 70 percent of the children in the study began experiencing psychosis before the age of 13. And 28 percent met the official criteria for schizophrenia, and had persistent, unrelenting symptoms. All underwent systematic testing for DNA duplication and deletion, which together are called copy number variants or CNVs. Eight percent were found to have CNVs known to be associated with neurodevelopmental disorders. This made CNVs as common as in children with autism, who are often screened for CNVs in the clinic.

Many parents feel as though they are being put under a microscope or even accused of triggering their children’s symptoms.”

“Our findings make a strong case for chromosomal microarray testing in any child or adolescent with psychosis,” he says. Katherine Brownstein, Master of Public Health, Ph.D. In the Department of Genetics and Genomics at Boston Children’s, who co-directed EPICenter and co-led the study with Elise Douard at the University of Montreal. “Testing often leads to household closures and can help advance research.”

Ending years of uncertainty

Families are often relieved to learn that their children’s psychotic symptoms have a biological component. Their children’s psychosis may have been misdiagnosed, interpreted as a normal developmental stage, and attributed to stressors such as being bullied, or even blaming bad parenting.

“Many parents feel as if they are being put under a microscope or even accused of triggering their children’s symptoms,” says Gonzalez Heydrich. “It parallels what happened with autism a generation ago.”

In other cases, the psychosis may be missed because the child also has autism or another developmental disorder. More than a third of the children in the study had an autism spectrum disorder diagnosis, 12 percent had an intellectual disability, and 18 percent had a history of seizures.

Finally, well-meaning clinicians may be reluctant to stigmatize a child with a diagnosis of psychosis, preferring to watch and wait. But if a child has symptoms of psychosis, finding a CNV may warrant trying antipsychotic medications to see if they help.

“The longer psychosis goes untreated, the more difficult it will be to treat later,” says Glan. “If we can deal with it early and appropriately, the child will likely do better over the course of his life.”

How can parents recognize early psychosis?

Many children have behaviors that may seem like psychosis, such as having an imaginary friend. But true psychosis disturbs children and is out of their control, say Gallan and Gonzalez Heydrich.

In some children, psychotic symptoms come and go. Psychosis can appear when a child is under stress, anger, severe depression, or mood swings. But in children with true schizophrenia, symptoms are persistent and extreme. This is very rare in children under the age of 10, but becomes less rare in adolescence and early adulthood. From a perspective perspective, schizophrenia affects only 1 to 2 percent of the general population, including adults.

The longer psychosis goes untreated, the more difficult it is to treat later. If we can treat it early and appropriately, the child will likely do better over the course of his life.”

Early signs of psychotic illness may be general. The child may become withdrawn. Their daily functioning may deteriorate, sometimes dramatically, and interfere with school and relationships. Or they may have seizures they haven’t had before. Later, hallucinations and paranoia may take hold, causing the child to see and hear things that are not there, and often feel threatened.

“It’s not just that the child thinks someone is talking about him because he is socially anxious,” Gonzelez-Heydrich says. “It’s multiple voices criticizing and scaring them and telling them to do bad things. Or the feeling that strangers are staring at them and plotting to harm them.”

From research to support and care

Besides encouraging treatment, finding a CNV in a child with psychosis allows other family members to screen them to see if they are at risk. Some CNVs can also cause medical complications such as seizures, heart problems, or weak blood vessels that can be monitored and treated. Family members who test positive for CNV may also be at risk of developing such medical problems, even if they do not have behavioral symptoms.

Brownstein, who is also the scientific director of Manton Center for Orphan Disease Research At Boston Children’s, he supervised the test. She notes that finding a CNV can help parents connect with other families for reassurance and support. Also, once a CNV is found, scientists can study what the missing or duplicated genes do. This may lead to a better understanding of the origins of early psychosis and possibly to better antipsychotic drugs, which have not changed much since the 1950s.

“We don’t have demographics at the moment,” Brownstein says. “But when parents come together, they can organize and identify research dedicated to their CNV. We can study their children as a group and identify effective treatments faster.”

Learn more about Early Psychosis Investigation Center (EPICenter) In Boston for children.

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