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Activity in stem cell-derived neurons predicts neural deficits in people with schizophrenia

17 January 2022
Appeared in BioNews 1128

For the first time, a biomarker for symptoms of psychiatric illness has been discovered using neurons derived from schizophrenia patients' own cells

Few psychiatric illnesses have known biomarkers distinguishing healthy cells from diseased cells. US scientists studied neurons grown in the lab that were developed from induced pluripotent stem cells (iPSCs) obtained from schizophrenia patients and neurotypical people. In the brain, neurons communicate with each other using electrical activity generated by proteins called ion channels. They studied the electrical activity of the iPSC derived neurons and compared it with clinical scores, and observed differences in activity patterns that correlated with specific symptoms in patients.

'We studied physiological characteristics of stem cell-derived neurons and determined which neurons predicted meaningful clinical features of the disorder in actual patients, the living donors of the cells' said first author Dr Stephanie Page from the Lieber Institute for Brain Development in Baltimore, Maryland. 

'We found a pattern of cell activity that correlated with the degree of psychosis in the donors. We found another pattern of activity that predicted with almost absolute accuracy the level of cognitive impairment of the donors. These clinical features, psychotic symptoms and cognitive deficits, are the cardinal manifestations of schizophrenia.'

The work, published in PNAS, was unique for the variety of clinical data that was available from participants. Researchers were provided with the results from multiple cognitive tests, diagnostic history and genetic information obtained from genome-wide association studies for the 13 patients and 15 neurotypical individuals. 

In parallel, researchers made recordings of separate types of electrical activity produced by different ion channels from the iPSC-derived neurons. When this data was compared to the cognitive and diagnostic scores, statistical associations were discovered that linked three specific types of electrical activity to the presence and severity of the key symptoms of schizophrenia in patients. 

Current diagnosis of schizophrenia is based on symptoms, which usually do not present until adulthood. Biomarkers for other aspects of psychiatric disease have been recently studied as a means to improve treatment in patients and as a tool for researching the illnesses in a laboratory setting.

'These exciting results build our confidence in the usefulness of modelling schizophrenia with patient-derived stem cells,' said Dr Brady Maher, the study's lead investigator. 'They open the door to personalised medicine, to the possibility of predicting before someone develops schizophrenia how severe the symptoms will be – well before a patient's first psychotic episode.'

Electrophysiological measures from human iPSC-derived neurons are associated with schizophrenia clinical status and predict individual cognitive performance
Proceedings of the National Academy of Sciences of the United States of America |  18 January 2022
New study finds neurons derived from stem cells predict psychosis and cognitive deficits in individuals with schizophrenia
Lieber Institute for Brain Development |  11 January 2022
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