Mutations in PCM1, a gene crucial to neuronal cilia function, have been connected with schizophrenia, according to a recent study.
A recent study1 has determined defective cilia in the brain may be associated with some forms of severe schizophrenia.
Experimental animal models showed deleterious mutations in a gene necessary for neuronal cilia were tied to symptoms resembling schizophrenia. A cohort of patients with treatment-resistant schizophrenia had similar mutations. This strengthened the theory that pericentriolar material 1 (PCM1) mutations, or shortened cilia, contribute to schizophrenia.
“I cannot definitively say if it is the worsening cilia length that is causing this schizophrenic behavior, or if that is one part of the phenotype of these mutations. But, this could explain why some patients are resistant to treatment,” said senior author Nicholas Katsanis, PhD, Associate Chief Research Officer For Translational Research at the Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago.2
Small and hair-like, cilia are found on the surface of cells and are critical for embryonic development. They are present throughout the brain on the surface of neurons. However, according to Katsanis, the role of cilia in the brain is undetermined.
The study examined PCM1, a gene vital to cilia function. When PCM1 is deleted in cell culture systems, cells do not form cilia and usually die; however, when researchers created mice that lacked PCM1, they were surprisingly born healthy. As the mice reached adolescence, they began to show behavioral problems.
“This was odd and unexpected,” Katsanis said. “But this observation tracks well with the timeline of schizophrenia development in people, where it is often first diagnosed during puberty.”2
Then, by studying cilia-related genes in a cohort of patients with severe schizophrenia who failed to respond to potent antipsychotic drugs, researchers found an excess of individuals with rare mutations in PCM1 compared with those unaffected.
While further studies are required to prove the claim that shortened cilia causes schizophrenia, the findings do suggest a link between PCM1 mutations and schizophrenia.
1. Monroe TO, Garrett ME, Kousi M, Rodriguiz RM, et al. PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia. Nature Communications. November 19, 2020. https://www.nature.com/articles/s41467-020-19637-5
2. Ann and Robert H. Lurie Children's Hospital of Chicago. Cilia Defects Linked to Schizophrenia. News release. November 24, 2020. https://www.newswise.com/articles/cilia-defects-linked-to-schizophrenia?sc=mwhr&xy=5013482