Scientists dig deeper into the genetics of schizophrenia by evaluating microRNAs

May 11, 2008
Human Chromosome
Shown here is human chromosome 22 and the piece of the chromosome missing in some patients with schizophrenia. Loss of this chromosomal piece (22q11) is the only known recurrent copy number mutation associated with schizophrenia. The corresponding region on mouse chromosome 16 is indicated along with the position of the engineered deletion in the mouse model. The engineered deletion results in alterations in microRNA production and as a result neuronal and behavioral deficits. © 2008 Columbia University

Researchers at Columbia University Medical Center have illuminated a window into how abnormalities in microRNAs, a family of molecules that regulate expression of numerous genes, may contribute to the behavioral and neuronal deficits associated with schizophrenia and possibly other brain disorders.

In the May 11 issue of Nature Genetics, Maria Karayiorgou, M.D., professor of psychiatry, and Joseph A. Gogos, M.D., Ph.D., associate professor of physiology and neuroscience at Columbia University Medical Center explain how they uncovered a previously unknown alteration in the production of microRNAs of a mouse modeled to have the same chromosome 22q11.2 deletions previously identified in humans with schizophrenia.

“We’ve known for some time that individuals with 22q11.2 microdeletions are at high risk of developing schizophrenia,” said Karayiorgou, who was instrumental in identifying deletions of 22q11.2 as a primary risk factor for schizophrenia in humans several years earlier. “By digging further into this chromosome, we have been able to see at the gene expression level that abnormalities in microRNAs can be linked to the behavioral and cognitive deficits associated with the disease.”

The investigators modeled mice to have the same genetic deletion as the one observed in some individuals with schizophrenia and examined what happens in the expression of over 30,000 genes in specific areas of the brain. When they discovered that the gene family of microRNAs was affected, they suspected that the Dgcr8 gene was responsible. The Dgcr8 gene is one of the 27 included in the 22q11.2 microdeletion and has a critical role in microRNA production, so this was a logical hypothesis. Indeed, when they produced a mouse deficient for the Dgcr8 gene, and tested it on a variety of cognitive, behavioral and neuroanatomical tests, they observed the same deficits often observed in people with schizophrenia.

“Our studies show that alterations in microRNA processing result in synaptic and behavioral deficits,” said Dr. Gogos. Drs. Karayiorgou and Gogos have partnered together to decipher the role of individual genes from 22q11 in the development of schizophrenia by using human genetics and animal model approaches.

The significance of this work is that it implicates a completely novel, previously unsuspected group of susceptibility genes and brings investigators a step closer to understanding the biological mechanisms of this disorder. Implication of such a large family of genes (the most recent estimate puts the number of human microRNAs at at least 400 that influence the expression of as many as a third of all genes) could partly account for the genetic complexity associated with this devastating disorder and explain some of the difficulties that the researchers have encountered in their efforts to pinpoint individual genes.

“Our hope is that the more we know about the genes involved in schizophrenia, the more targeted treatment can be,” said Dr. Gogos.

“Much in the way that cancer patients who have tested for a particular gene, such as BRAC1, can be tested and then treated with protocols designed specifically for them, we want to be able to know enough about the schizophrenic brain to target treatments to individual patients.”

The next step for the researchers is to find the many genes whose expression is controlled by the identified deficient microRNAs, which could in turn be involved in the pathogenesis of schizophrenia. Much more study and identification of other genetic variants must be done to further illuminate the disease’s genetic underpinnings, according to Drs. Karayiorgou and Gogos.

Source: Columbia University

Explore further: 'Master key' gene has links to both ASD and schizophrenia

Related Stories

'Master key' gene has links to both ASD and schizophrenia

November 5, 2018
Recent studies of complex brain disorders such as schizophrenia and autism spectrum disorder (ASD) have identified a few "master keys," risk genes that sit at the center of a network of genes important for brain function. ...

Adolescent THC exposure alters neurons/gene networks associated with psychosis risk

October 18, 2018
Young adults with exposure to THC (the psychoactive component of cannabis) during adolescence have alterations in the structure of neurons and gene expression within these brain cells, which are critical for maintaining synaptic ...

Researchers use genetics to predict response to antipsychotic medications

November 5, 2018
Genetics can be used to predict a patient's response to antipsychotic drug treatment for schizophrenia, according to a recent study by investigators at The Feinstein Institute for Medical Research. The findings were published ...

Researchers explain how LSD changes perception

October 26, 2018
Psychedelic drugs such as LSD have a profound impact on human consciousness, particularly perception. Researchers at Yale and the University of Zurich provide new insight into the psychedelic effects of LSD on the brain and ...

Brain cells called astrocytes have unexpected role in brain 'plasticity'

October 18, 2018
When we're born, our brains have a great deal of flexibility. Having this flexibility to grow and change gives the immature brain the ability to adapt to new experiences and organize its interconnecting web of neural circuits. ...

Researchers use brain cells in a dish to study genetic origins of schizophrenia

October 16, 2018
A study in Biological Psychiatry has established a new analytical method for investigating the complex genetic origins of mental illnesses using brain cells that are grown in a dish from human embryonic stem cells. Researchers ...

Recommended for you

Progress in genetic testing of embryos stokes fears of designer babies

November 16, 2018
Recent announcements by two biotechnology companies have stoked fears that designer babies could soon be an option for those who can afford to pick and choose which features they want for their offspring. The companies, MyOme ...

Gene editing possible for kidney disease

November 16, 2018
For the first time scientists have identified how to halt kidney disease in a life-limiting genetic condition, which may pave the way for personalised treatment in the future.

DICE: Immune cell atlas goes live

November 15, 2018
Compare any two people's DNA and you will find millions of points where their genetic codes differ. Now, scientists at La Jolla Institute for Immunology (LJI) are sharing a trove of data that will be critical for deciphering ...

Ashkenazi Jewish founder mutation identified for Leigh Syndrome

November 15, 2018
Over 30 years ago, Marsha and Allen Barnett lost their sons to a puzzling childhood disease that relentlessly attacked their nervous systems and sapped their energy. After five-year-old Chuckie died suddenly in 1981, doctors ...

Drug candidate may recover vocal abilities lost to ADNP syndrome

November 15, 2018
Activity-dependent neuroprotective protein syndrome (ADNP syndrome) is a rare genetic condition that causes developmental delays, intellectual disability and autism spectrum disorder symptoms in thousands of children worldwide. ...

The puzzle of a mutated gene lurking behind many Parkinson's cases

November 15, 2018
Genetic mutations affecting a single gene play an outsized role in Parkinson's disease. The mutations are generally responsible for the mass die-off of a set of dopamine-secreting, or dopaminergic, nerve cells in the brain ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.