New Genetic Link Found to Childhood-Onset Schizophrenia

Childhood-onset schizophrenia symptoms are similar to schizophrenia experienced by adults but is an extremely rare condition with a prevalence of about 1 in 40,000. Due to its rarity, there is a lack of epidemiological incidence data with diagnoses based on standardized clinical assessments.

As with adult schizophrenia, children with the chronic mental disorder experience cognitive, behavioral, and emotional problems, along with hallucinations, delusions, and highly disordered thinking. In childhood however, the condition impairs development, lowers educational performance, and hinders social relationships. While individuals with schizophrenia typically begin to have symptoms in their early 20s, early-onset schizophrenia can begin in those under the age of 18 years. Very early cases of schizophrenia begin before the age of 13 and have been observed in children as young as 6 years of age.

Researchers have found that children with very early-onset schizophrenia have a higher rate of chromosomal abnormalities than adults with the disease, suggesting that onset in childhood has a stronger genetic predisposition. In a new study published in the journal Molecular Psychiatry, scientists from Canada’s Montreal Neurological Institute and Hospital (The Neuro) and McGill University say they’ve discovered novel genes associated with childhood schizophrenia. The researchers say that while the heritability of schizophrenia is estimated to be 80%, identifying the genes associated with the mental disorder has been challenging.

By researching childhood-onset schizophrenia, which is more rare and extreme, the scientists hoped to identify new genetic variants of the mental disease. Analyzing genetic data from 19 patients under the age of 13 with childhood schizophrenia whose parents did not have the disorder, the researchers discovered that 3 patients showed a mutation in the ATP1A3 gene, while another 3 showed genetic variants in the FXYD genes—a gene family contributing to the normal functions of ATP1A3. Previous reports have found mutations affecting ATP1A3 in other rare neurological childhood diseases, and the study authors note that the new findings suggest that the gene plays a role in neurological diseases as well as psychiatric disorders.

In an interview with Rare Disease Report^®, the study’s first author, Boris Chaumette, MD, PhD, said that in 2 cases, the study team found that the parents did not carry the mutation and it was only present in the child. In 4 cases, the mutation was present in only 1 parent.

By identifying these genetic variants, the researchers say they’ve taken a step toward the development of treatment for childhood-onset schizophrenia. “Childhood-onset schizophrenia responds poorly to treatment and the prognostic is worse than in adult-onset schizophrenia,” Dr. Chaumette said. “We can propose to challenge mutation carriers by oral ATP supplementation as this treatment as shown clinical improvement in one carrier in the literature.”

For now, the new data enables doctors to diagnose the condition and provide families with genetic information. “Our identification of genes responsible for this terrible condition means researchers can focus on developing drug therapies to give patients better outcomes,” said Dr. Chaumette in a recent statement. “It will also decrease the guilt the children’s parents often feel, because they think they somehow caused their child’s condition.”