Columbia Scientists Reverse Core Symptoms of Schizophrenia in Mice
Thu, September 29, 2022

Columbia Scientists Reverse Core Symptoms of Schizophrenia in Mice

Schizophrenia is a serious mental disorder that needed help from professionals / Photo Credit via 123RF


A team of researchers from Columbia University was able to eliminate the core symptom of schizophrenia in mice. This challenged the long-standing belief that memory issues in such mental illness cannot be repaired the moment the symptoms appear, reports Columbia's Zuckerman Institute.


Understanding schizophrenia and its core feature

Schizophrenia is a severe and chronic mental disorder that affects how a person behaves, feels, and thinks. People with schizophrenia may appear like they have lost touch with reality, as they have delusions, hallucinations, thought disorders, and movement disorders. The condition is not easy to understand and treat. Its core feature is cognitive impairment, including trouble with memory.


Addressing psychotic vs. cognitive symptoms

To this day, there are no standardized treatments to target the working memory impairments of patients diagnosed with schizophrenia. The same goes for pharmaceutical and therapeutic. Although there are medications used to treat schizophrenia, they largely address the psychotic symptoms and not the cognitive aspects.

The Columbia University team now believes that there is a way to treat the working memory deficits associated with schizophrenia. To come up with such resolve, the team used a mouse model and successfully reversed the mutation of gene SETD1A, a protein-coding gene that is associated with schizophrenia. The team wrote in their paper that appeared in the scientific journal Neuron that mutations to SETD1A confer a “large increase” in schizophrenia risk. 


There are existing medications for people who diagnosed with Schizophrenia / Photo Credit via 123RF


Zuckerman Institute’s neuroscientist Joseph Gogos, who is also the principal investigator of the study, said that they were surprised to observe that restoration of SETD1A gene activity in the brain of the mouse models also restored their learning. This showed that damage done by gene mutation when the brain was developing is not completely irreversible. 

“We found SETD1A  to be a genomic multitasker,” Lomvardas lab’s postdoctoral research scientist and the paper’s co-first author Enrico Cannavó, Ph.D., said. The team also found another gene called LSD1. They said that when such a gene is switched off, it will also nullify the harmful effects of SETD1A. As a result, the memory of the mouse models improved dramatically. What was even more striking was what they observed in the brains of the animals. That is, their axons grew in the same patterns as what the researchers observed in a healthy mouse brain.


Drug repurposing

Drug repurposing or repositioning is a drug development strategy, which involves the identification and investigation of already approved drugs for new uses or therapeutic purposes. The Columbia University team used this strategy by using a drug that is currently in development to help treat leukemia. They said that their work helped repair the dysfunctional brain cells of the mouse models and brought back their working memory to a healthy state.

Dr. Gogos added that many patients diagnosed with schizophrenia have the same issues that are caused by SETD1A mutation.



Purpose of the study

Gogos stated further that the results of their findings can be used to identify drugs that can restore the normal cellular and cognitive function in the adult brain at the onset of schizophrenia.

The team also wrote that although well-known symptoms such as auditory hallucinations, delusions, and paranoia can be controlled with the help of antipsychotic medication, problems that happen in the working memory remain untreatable. Working memory is an important brain process that is used to recall and retain information quickly such as recalling a new phone number just long enough to dial it. The working memory of people diagnosed with schizophrenia is severely impaired that it alters their decision-making, perception, and reasoning.


Schizophrenia: statistics and facts

American Addiction Centers Resource MentalHelp shares that about 1 percent of the world’s population is diagnosed with schizophrenia. Approximately, 3.2 million or 1.2 percent of Americans have such a mental disorder. Schizophrenia is most likely to occur in early adulthood and relatively rare in older adults and children. The peak of vulnerability for people diagnosed with schizophrenia is between ages 16 and 25. 

Men and women have different patterns of susceptibility when it comes to schizophrenia symptoms. For men, their peak of vulnerability is between ages 18 and 25. For women, their vulnerability peaks twice: first between 25 and 30 and then 40 onward.



Schizophrenia support forums and recovery information site likewise details that 10 years after being diagnosed with schizophrenia, and provided there was earlier treatment, 25 percent can completely recover, 25 percent can be considered relatively independent already, 25 percent considered “improved” but still requires extensive support network, 15 percent unimproved cases or hospitalized, and 10 percent dead mostly because of suicide.

People with schizophrenia are homeless or live in shelters (6 percent), in prisons (6 percent), in the hospital (5 to 6 percent), in nursing homes (10 percent), or with a family member (25 percent). They can also live independently (28 percent) or in supervised housing (20 percent).