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Defective Cilia May Lead To Schizophrenia

by Karishma Abhishek on November 29, 2020 at 4:02 PM
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Defective Cilia May Lead To Schizophrenia

Defects in neuronal cilia may trigger severe schizophrenia, as per a study published in Nature Communications. This may be due to a deleterious mutation in the PCM1 gene, which is vital for the cilia's development and function.

Schizophrenia is a brain disorder, characterized by hallucinations, delusions, and behavioral issues. Small hair-like structures that are present on a cell's surface is called cilia. These are important for the development of a cell at the embryonic stage, which upon failure, would halt the developmental process.

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Neuronal cilia are present on the surface of neurons - brain cells. Though the exact mechanism remains unclear, several psychiatric illnesses have been linked with ciliary defects.

Genetic mechanisms:

The study conducted in mouse models that lacked PCM1 showed that the mice did not die - as evidenced by earlier researches, but they survived to develop behavioral issues during adolescence. This was confirmed in even the cohort of human schizophrenia patients, where they had PCM1 mutation and no response to antipsychotic drugs such as clozapine.
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Later the mice also demonstrated defects in the dopamine receptors regulating genes in neurons — the same receptors targeted by clozapine.

"Our working model is that in the absence of PCM1, fewer dopamine receptors rise to the surface of the cell . If you have such a deficit, your ability to respond to dopamine drugs is reduced", says Nicholas Katsanis, Ph.D., 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 and senior author of the study.

Though genetic mutations causing ciliary defects greatly link the reasons for developing schizophrenia or other psychiatric illness, the study affirms that a more diverse approach to data is needed for further exploration of the mechanisms associated with it.

"Most scientists would agree that schizophrenia is not a single disease, but rather the manifestations of hundreds of diseases put together. In that respect, large genome-wide sweeps help us discover common truths about the end disease, but not about its subtypes. So, although genome-wide analyses are a great step, we must now dig deeper", said Katsanis.

Schizophrenia Facts

  • Schizophrenia affects 20 million people worldwide.
  • Schizophrenic people are 2-3 times more likely to die early than the general population.
  • More than 69% of people with schizophrenia are not receiving appropriate care.
  • Schizophrenia is treatable.


Source: Medindia
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