Team uses chemical compound to restore affected brain regions; findings could lead to new treatment strategies
Researchers have successfully disrupted a genetic chain of events in a mouse model of schizophrenia and reversed memory deficits, one of the disorder’s most difficult-to-treat symptoms. This discovery—which builds upon decades of early-stage research—could lead to more effective therapies for the cognitive symptoms of schizophrenia, a psychiatric disorder that affects more than 21 million people worldwide.
In a paper published today in the journal Neuron, scientists at Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute,Columbia University Medical Center (CUMC) as well as the New York State Psychiatric Institute (NYSPI) used a chemical compound to regrow connections between brain cells, or neurons, which in turn restored memory deficits. The abnormal or stunted growth of neurons in the brain’s memory centers is a key indicator of schizophrenia.
The study was performed in mice with a specific genetic mutation known as the 22q11.2 microdeletion. This mutation, which occurs in one percent of people with schizophrenia, is the single largest genetic risk factor for the disease.
“With these findings, we showed that restoring cellular connections reversed memory deficits—a symptom of schizophrenia for which there is no effective treatment,” said Joseph Gogos, MD, PhD, a principal investigator at the Zuckerman Institute, professor of physiology and neuroscience at CUMC and a senior author of the paper. “This represents an invaluable new strategy for treating schizophrenia and highlights the critical importance of basic biological research in psychiatric disorders. Understanding how schizophrenia originates in our model lends critical insight into the disorder as a whole, paving the way for improved treatment options that have thus far remained elusive.”
Paranoia, auditory hallucinations and delusions are some of schizophrenia’s most well known symptoms and can often be controlled with antipsychotic medication. However, other symptoms—like severe disruptions to short-term and verbal memory, reduced attention and a decrease in IQ—have remained largely untreatable. Memory deficits can interfere with an individual’s ability to maintain relationships or a job—essentially cutting them off from the world around them.
“Memory deficits are now considered a core feature of schizophrenia and are believed to be strongly tied to the disorder’s underlying biology,” said Joshua Gordon, MD, PhD, associate professor of psychiatry at CUMC, a research scientist at NYSPI and a senior author of the paper. “Until we can shed light on that biology, these symptoms remain virtually impossible to treat.”
To address this, Dr. Gogos has spent nearly 20 years working to uncover the biological basis of schizophrenia. He and his collaborators developed a laboratory mouse model that exhibited the 22q11.2 microdeletion.
“Schizophrenia affects about one in every 100 people, but for those with a 22q11.2 microdeletion, that chance jumps to one in three,” said Dr. Gogos. “22q11.2 microdeletions remain the single greatest genetic risk factor for developing schizophrenia. This is why our model has proved invaluable in allowing us to trace schizophrenia back to its beginnings.”
In a study published last year, Drs. Gogos, Gordon and their research team revealed how the 22q11.2 microdeletion leads to weaker connections between neurons in key brain regions, resulting in schizophrenia’s memory deficits.
“Normally, neurons grow long branches that connect across long distances, forming tightly interconnected circuits,” said Dr. Gordon. “However, in our mouse models, these branches were stunted in the hippocampus and prefrontal cortex—two regions crucial for memory. Further experiments revealed why: a protein called Gsk3? was clogging the brain.”
Last year’s study showed that the 22q11.2 microdeletion kickstarts a chain reaction that boosts Gsk3? activity right from birth. Overactive Gsk3? stunts the growth and development of neurons in the brain’s memory centers. Over time, this hampers their ability to form strong connections.
In the new study, the researchers tested whether suppressing Gsk3? activity could reverse the damage that ultimately leads to schizophrenia’s memory deficits.
In a series of experiments, the researchers treated their mouse models at a young age (between seven and 28 days after birth), with a chemical compound that blocked Gsk3? activity. Almost immediately, they began to see a difference. As Gsk3? activity dropped, the neurons branched out and formed connections with their neighbors. Communication between brain regions was restored, and—importantly—the mice showed no memory deficits.
“Our work suggests that Gsk3? could be considered a potential target for treating some symptoms of schizophrenia—though there are limitations,” said Dr. Gordon. “For example, whether the same treatment might work in other models of schizophrenia that do not have the 22q11.2 microdeletion. Also, we treated the mice at a young age, but schizophrenia normally presents in adolescence and young adulthood.”
“We’re currently planning to test whether blocking Gsk3? during that equivalent age in our models would also have the same positive effect,” added Dr. Gogos.
“Schizophrenia is a complex disorder—there is no single cause—but disrupted communication between the hippocampus and prefrontal cortex may be a common thread running through many of them,” said Vikaas Sohal, MD, PhD, assistant professor of psychiatry at the University of California, San Francisco School of Medicine, who was not involved with the study.
“The findings presented here by Drs. Gogos, Gordon and their team could lead to additional ways of restoring normal communication between these two brain regions—and thus provide effective treatments for schizophrenia that arise from a variety of causes.”
The Latest on: Schizophrenia
via Google News
The Latest on: Schizophrenia
Hotel Mira's Charlie Kerr Takes His Battle with Mental Illness to the Stage in Support of the B.C. Schizophrenia Society
on May 23, 2019 at 7:13 am
National Schizophrenia and Psychosis Awareness Day, a day devoted to raising awareness about psychosis, schizophrenia and other persistent mental illnesses. Hosted by the B.C. Schizophrenia ... […]
Re-Frame Re-Casts Schizophrenia and Psychosis
on May 22, 2019 at 7:14 pm
VANCOUVER, May 22, 2019 /CNW/ - On May 23rd, the B.C. Schizophrenia Society (BCSS) is hosting Re-Frame: The Broad Impacts of Schizophrenia, an educational meeting focused on the recovery journey ... […]
Recognizing the complexity of schizophrenia is crucial to its treatment
on May 22, 2019 at 12:05 pm
Schizophrenia, a condition that afflicts about 1 percent of the U.S. population, is a "chronic and severe mental disorder that affects how a person thinks, feels, and behaves," according to the ... […]
'Game Changer' for Schizophrenia on the Horizon?
on May 22, 2019 at 7:06 am
SAN FRANCISCO — The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to a potentially first-in-class psychotropic agent with a completely different mechanism of ... […]
Could a broccoli sprout extract help treat schizophrenia?
on May 20, 2019 at 11:06 pm
The current schizophrenia treatments rely on antipsychotic drugs that come with unwanted side effects. However, new research has found that a chemical called sulforaphane could reduce and even prevent ... […]
My Brother Tom’s Schizophrenia
on May 20, 2019 at 3:23 pm
My brother Tom’s slide into homelessness occurred in stages. We never knew exactly when or how he lost his apartment, or came to crash on friends’ couches, or began having run-ins with the cops. Nor ... […]
Quetiapine for schizophrenia and bipolar disorder
on May 20, 2019 at 4:20 am
Quetiapine is an atypical antipsychotic, which is used to treat schizophrenia, bipolar disorder or depression. It is available as standard tablets, slow release tablets or liquid (20mg/ml). The ... […]
Schizophrenia, Epilepsy May Hike Risk of Early Death
on May 19, 2019 at 5:09 am
Patients with both schizophrenia and epilepsy are particularly vulnerable to early death, according to a new Danish study from Aarhus University. The findings reveal that more than 25 percent of ... […]
Genetic Hotspot May Drive Psychosis in Schizophrenia, Bipolar Disorder
on May 17, 2019 at 6:58 am
Scientists have identified an epigenetic hotspot which they believe is linked to the dopamine-induced psychosis found in schizophrenia and bipolar disorder. The findings, published in the journal ... […]
Study: Many patients with schizophrenia and epilepsy die before reaching the age of fifty
on May 16, 2019 at 12:16 pm
Patients who suffer from schizophrenia and epilepsy are particularly vulnerable. In the study, the researchers followed more than 1,5 mio. people and classified them according to whether they were ... […]
via Bing News