The onset of schizophrenia in children under 13 is extremely rare, but it does occur. When it does, its symptoms are far more severe and persistently debilitating than for patients who develop the condition at a later stage in life. Now a ten-year research effort has found new genetic factors that help to understand the causes of this particular form of schizophrenia.
There has been a lot of research into the role genetics play in the onset of schizophrenia, but most of this work has focused on the common form that manifests in adolescence and early adulthood. Significantly less attention, however, has been paid to the rarer and more severe form of schizophrenia that manifests in children under 13 years of age.
Childhood Onset Schizophrenia (COS), which has an estimated prevalence of less than 0.04 percent, is very similar to other forms as it causes a range of problems associated with thinking, behavior, and emotions. However, COS tends to be more problematic as it has profound impacts on overall neuronal development, causing impairments in memory, abstract thinking, and emotional regulation.
COS is also difficult to diagnose as many children report unusual phenomena related to their thinking and perception, which comes from their imaginations and fantasies, especially when processing mental distress. There is also the challenge that autism and anxiety disorders, as well as post-traumatic disorders, can sometimes manifest in ways that are close to psychosis. But now, new research has taken an important step in helping improve diagnostic techniques for the future.
At the end of March 2023, the Hebrew University of Jerusalem announced the end of a decade-long study into the genetic contribution toward COS. The research was conducted in collaboration with Eitanim of the JMHC and Ness Ziona psychiatric hospital in central Israel, Sheba medical center, and researchers from Columbia University, New York.
The research team was interested in whether there were specific genetic factors associated with COS. “Childhood schizophrenia has an even stronger genetic basis than later-onset schizophrenia”, Dr Anna Alkelai, Research Associate at the Institute for Genomic Medicine, Columbia University and first author on the publication said in a statement. “The disorder is more common among first-degree relatives. Therefore, there are reasons to deduce that in this population it will be easier to crack the genetic component in the etiology of the disease.”
According to Professor Yoav Kohn, the study’s senior investigator and former Chairman of the Psychiatry Department at Hebrew University-Hadassah School of Medicine and Director of the child and adolescent psychiatry ward at Eitanim, genetic research into schizophrenia has been conducted on tens of thousands of patients collected by hundreds of researchers across the world who collaborate in a large international consortium. This work has highlighted clues that associate more than 100 genetic regions with the condition, but few studies find mutations that explicitly relate to schizophrenia’s etiology. Moreover, many of the genetic changes that appear in adult-onset schizophrenia are also not unusual in people without it. This means the overall research has not yet been of use in terms of diagnosing or treating the disorder.
In this latest study, the team examined 37 children with COS and their families who were recruited by the Department of Child and Adolescent Psychiatry, Jerusalem Mental Health Center at Eitanim Psychiatric Hospital. The researchers projected that a relatively large sample of patients with this disorder could be collected and compared to the existing global research for genetic insights. They then used exome sequencing (ES), an approach used to sequence all the protein-coding regions of genes in a genome, to assess the 37 participants and their families.
The results show that a genetic mutation was found in seven of the children and their families, which may provide a cause for COS. The implicated genes were ANKRD11, GRIA2, CLCN3, CLTC, IGF1R and MICU1. Some of these genes have already been linked to specific psychiatric phenotypes, so the new evidence not only supports existing work but expands on it.
The researchers note that results can be used to help improve the diagnosis and more targeted treatments for COS. This can further help families understand their child’s condition and enable genetic counseling for family members who want to have children.
“The finding of mutations that explain the disease in approximately 20% of childhood schizophrenia patients opens far-reaching diagnostic and therapeutic possibilities”, Professor Kohn explained. “For example, a mutation was found in the GRIA2 gene that codes for a sub-unit of the glutamate receptor, the main excitatory neurotransmitter in the central nervous system. Mutations in this gene have previously been associated with language and behavioral problems but not schizophrenia. Another mutation found homozygously in the gene MICU1, is known to cause mitochondrial damage with muscle weakness, developmental problems and learning disabilities, but has not previously been reported to be associated with schizophrenia. Therefore, these findings may also expand the definition of the known syndrome phenotype, and aim at new targets for drug treatment.”
The study is published in Schizophrenia Research.
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