New Genetic Findings Shed Light on Origins of Schizophrenia
A recent study led by Harvard Medical School clinician-scientist Eduardo Maury has identified two genetic deletions associated with schizophrenia that likely occur during early gestation. The findings, published in Cell Genomics, provide new insights into the origins of the neurological disorder and could potentially lead to early prevention strategies.
Schizophrenia, which affects approximately 1 in 300 people worldwide, is known to be influenced by a combination of genetic and environmental factors. While it typically manifests in early adulthood, there is growing evidence suggesting that the physiological changes underlying the disorder may originate in early pregnancy or as a result of gestational complications.
Previous studies have indicated that disorganized brain cells and specific genes in the placenta active during complicated pregnancies are associated with schizophrenia. Building on this research, Maury and his team examined genetic data from nearly 25,000 individuals with or without schizophrenia.
The researchers identified two genes, NRXN1 and ABCB11, that appear to be associated with schizophrenia when copies of the genes are missing in utero. The alterations, called copy number variations, involve the duplication or deletion of gene copies or long stretches of DNA. While some copy number variations can be inherited, contributing to around 5 percent of schizophrenia cases, the deletions of NRXN1 and ABCB11 in this study were not inherited from parents.
The NRXN1 gene is known to play a role in transmitting signals between brain cells, and previous research has linked inherited mutations in this gene to schizophrenia. However, the study by Maury and colleagues focused on somatic mutations, which are acquired during early development or later in life and are only present in a fraction of body cells.
Surprisingly, the researchers also found deletions within the ABCB11 gene in schizophrenia cases that did not respond to antipsychotic medications. While this gene is primarily known for encoding a liver protein, its connection to schizophrenia is less certain.
The prevalence of partial NRXN1 deletions in the schizophrenia cases examined was significantly higher than in population-level databases, suggesting a potential role in the development of the disorder. The study concludes that these alterations in NRXN1 and ABCB11 “may contribute a small but significant part of the genetic architecture of schizophrenia.”
Further research is needed to fully understand the extent of their contribution and the mechanisms through which these genetic deletions lead to schizophrenia. However, the findings offer hope for early prevention strategies and a deeper understanding of the origins of this complex neurological disorder.