Genetic cause of childhood-onset schizophrenia potentially discovered - study

There are an estimated 200 Israelis suffering from childhood onset schizophrenia (COS) – a severe and rare form of the psychiatric disorder that emerges before the age of 13. The role of genetics in schizophrenia is significant and widely studied in the common form of the disease that appears in adolescence or early adulthood, but it has rarely been examined among young patients with COS.

The Hebrew University of Jerusalem has just announced that its 10-year research effort studying the genetic contribution to the causation of COS has now been completed. Conducted in collaboration between Eitanim of the Jerusalem Mental Health Center and Ness Ziona psychiatric hospitals, Sheba Medical Center at Tel Hashomer and Columbia University in New York City. The results were published in the journal Schizophrenia Research under the title “Genetic insights into childhood-onset schizophrenia: The yield of clinical exome sequencing.”

Prof. Yoav Kohn, former chairman of the Hadassah-University Medical Center’s psychiatry department and director of the child and adolescent psychiatry ward at the Eitanim Mental Health Center, was the senior researcher. “Childhood schizophrenia manifests similarly to adults including symptoms such as false thoughts, hallucinations, disorganized speech and behavior, in addition to a decrease in motivation and other symptoms. All of these are accompanied by impaired cognitive and behavioral function,” Kohn said.

Diagnosing childhood mental illnesses

“COS poses a diagnostic challenge to mental health professionals because many children report unusual phenomena in terms of thinking and perception, which can result from the normal use of imagination and fantasy to deal with mental distress. There is also a differential diagnosis with autism and anxiety disorders, and post-traumatic disorders that can even reach states close to psychosis.”

“Childhood schizophrenia has an even stronger genetic basis than later-onset schizophrenia. 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,” added Dr. Anna Alkelai, a research associate at the Institute for Genomic Medicine at Columbia University and first author of the study.

According to Kohn, genetic research in schizophrenia is today conducted on tens of thousands of patients collected by hundreds of researchers who collaborate in a large international consortium. Although clues have been found for the association of more than 100 genetic regions with the disease, these studies rarely find mutations in genes that can be definitively related to the etiology of the disorder. In addition, the genetic changes that are more common in adult-onset schizophrenia are also not uncommon in healthy people. Therefore, these findings are not conclusive and not yet useful in terms of improving the diagnosis and treatment of the disease.

There are two wards in Israel for psychiatric hospitalization of children under the age of 12 – the Eitanim and Ness Ziona hospitals. Researchers projected that a relatively large sample of patients with COS could be collected, compared to what has already been tested globally, to find the genetic cause of the disease. The study presents a diagnostic exome sequencing (a cost-effective technique when whole-genome sequencing is impractical or unnecessary) in 37 Israeli Jewish families.

The results of the study revealed that a genetic mutation was found in seven of the 33 children and their families who participated, which may explain the cause of the disease. The researchers note that the discovery of the mutation can be used in the future to help improve the diagnosis and find a specific treatment for the disease. This can further help families by providing an explanation for their child’s serious illness and enabling genetic counseling for healthy family members who wish 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,” Kohn concluded. “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.”