Neurons from stem cells can predict psychosis and cognitive deficits in schizophrenia, new study finds

For the first time, researchers have used neurons generated from human stem cells to predict basic characteristics of mental illness, a breakthrough that holds great promise for earlier diagnosis and better treatment of mental illness
.

Such as psychosis and cognitive deficits in people with schizophrenia

A study published by PNAS shows that the clinical symptoms of schizophrenia patients can be predicted by the activity of neurons derived from the patient's own stem cells
.

The link between this cellular physiology and symptoms such as delusions, hallucinations and cognitive alterations has never been discovered before
.

That said, no other study has shown a strong link between neural models derived from a patient's stem cells and clinically relevant features of the same person's psychiatric disorder

"These exciting results build our confidence in the validity of using patient-derived stem cells to model schizophrenia," said Brady J.
Maher, Ph.
D.
, a Lieber Research Fellow who led the study research
.

"They open the door to personalized medicine, making it possible to predict the severity of symptoms before someone develops schizophrenia -- long before the patient's first psychotic episode

In the United States alone, about 3.
5 million people suffer from schizophrenia, a debilitating brain disorder
.

People with schizophrenia experience delusions and hallucinations

Maher and his team have overcome a fundamental challenge facing researchers using stem cells to study brain diseases
.

Scientists have been able to use stem cell models to simulate the activity and molecular properties of many organs in the human body
.

These models can reproduce the pathogenesis of these organs in a petri dish

But for mental illnesses, such as schizophrenia or depression, there are no specific biological signatures that distinguish healthy brain cells from diseased ones
.

"Without an obvious abnormality to identify whether a cell is from a schizophrenic patient, there is no obvious way to confirm that any abnormality is the culprit," said Daniel R.

So the LIBD team did something unique, Weinberg said
.

They found differences in the function of ion channels, a type of protein that regulates electrical activity in the brain, in nerve cells from schizophrenia patients compared to normal individuals

"We investigated the physiological characteristics of stem cell-derived neurons and determined which neurons predicted meaningful clinical characteristics in actual patients (living cell donors)," explains Stephanie Page, lead author of the study
.

A pattern of cellular activity correlated with the level of psychosis was found in the donors

"When we ran these data, we were really surprised to see the strong link between cell physiology and schizophrenia symptoms," Maher said
.
"While we believed in the translational potential of stem cell-derived models, we couldn't imagine that these The activity of cells in a dish can so accurately predict the complex behavior of donors
.
"

Participants in the study were primarily young adult volunteers -- 13 with a high genomic risk and clinical diagnosis of schizophrenia, and 15 neurologically normal low-risk individuals
.
Subjects were screened extensively by obtaining medical, psychiatric, and neurological histories, physical examinations, developmental histories, MRI scans, and genome-wide genotyping
.

Dr.
Richard Straub, a senior research scientist at LIBD who processed both clinical and cognitive function data, said two things set the study apart
.
First, cell selection was based on differences in overall genomic risk for schizophrenia
.

A second feature of this study is that the researchers have access to virtually unprecedented clinical detail, not just diagnostic information and participants' performance on cognitive tests, but also other so-called "deep phenotypes," such as their How many cigarettes were smoked (smoking is common among people with schizophrenia), what medications they took, and details such as their symptom patterns
.
Other schizophrenia studies that have looked at stem cells have only the most rudimentary clinical data on the sample—whether a person has schizophrenia
.
But the wealth of data gives LIBD researchers the unique ability -- after extensive and rigorous testing of clinical characterization and cognitive performance -- to clearly discern how a patient's cell line matches their symptoms
.

Weinberg and his colleagues say they are optimistic that the unique findings could open up new avenues for treating the brain disorder
.
For this disease, treatment progress has stalled for years
.
While existing drugs for schizophrenia can suppress delusions and hallucinations, they do not address cognitive problems or address the underlying cause
.
"Having a basic laboratory cell model from living subjects that can predict the severity of their individual apparent disease is a potentially huge opportunity to discover new treatments," Weinberg said
.

"Current treatments for schizophrenia only target the symptoms of psychosis, such as hallucinations and delusions," Brady said
.
"Treatments for cognitive deficits are completely lacking
.
Our research is the first step in developing cognitive therapies for schizophrenia that can treat these negative symptoms
.
This will greatly reduce the suffering of these patients and their families
.
It also It can help people with schizophrenia live more productive lives
.
"

 

Article Title

Electrophysiological measures from human iPSC-derived neurons are associated with schizophrenia clinical status and predict individual cognitive performance