Nav: Home

Disrupted genetic clocks in schizophrenia-affected brains reveal clues to the disease

August 09, 2019

Rhythms in gene expression in the brain are highly disrupted in people with schizophrenia, according to a new University of Pittsburgh-led study.

The findings, published today by researchers from the Pitt's School of Medicine in the journal Nature Communications, also suggest that researchers studying schizophrenia-linked genes in the brain could have missed important clues that would help understand the disease.

"Our study shows for the first time that there are significant disruptions in the daily timing of when some genes are turned on or off, which has implications for how we understand the disease at a molecular level," said senior author Colleen McClung, Ph.D., professor of psychiatry at Pitt's School of Medicine.

Many bodily functions run on a 24-hour cycle, called a circadian rhythm, which extends to how genes are expressed within cells. Some genes turn on or off at certain times of the day or night.

In this study, McClung and colleagues analyzed gene expression data from the dorsolateral prefrontal cortex -- a brain region responsible for cognition and memory -- from 46 people with schizophrenia and 46 sex- and age-matched healthy subjects. The data was obtained from the CommonMind Consortium, a public-private partnership that has curated a rich brain tissue and data bank for studying neuropsychiatric disorders.

By knowing the time of death, the researchers were able to use a statistical method to determine changes in the rhythmicity of different genes, which revealed some interesting patterns.

McClung explained the findings by drawing an analogy of gene expression to electrical appliances in a house.

"In a normal house -- like a healthy brain -- let's say the lights are turned on at night, but the refrigerator needs to be on all the time. What we saw was that in a schizophrenia-affected brain, the lights are on all day and the refrigerator shuts off at night."

This is problematic, explains McClung, because it can affect how cells function. In their samples, the genes that gained rhythmicity were involved in how mitochondria -- the cell's powerhouse -- functions, and those that lost rhythmicity were linked to inflammation.

The results also have implications for other researchers studying the genetics of schizophrenia, according to Marianne Seney, Ph.D., assistant professor of psychiatry at Pitt's School of Medicine and the study's first author. By not considering circadian rhythms, they could be missing out on important findings.

When Seney and McClung compared gene expression in brains from people who died during the day, the control and schizophrenia subjects were not different, but in those who died at night, there were major differences, since genes that had gained a rhythm had hit their low point during the night.

Seney alludes to the analogy of the house. "If we only looked to see if the refrigerator was on during the day we would see no difference, but at night, there would be one."
-end-
Additional authors on the study include Kelly Cahill, John F. Enwright III, Ph.D., Ryan W. Logan, Ph.D., Wei Zong, and George Tseng, Sc.D., all of Pitt, and Zhiguang Huo, Ph.D., of the University of Florida.

The study was supported by National Institutes of Health grant MH111601 and the Brain and Behavior Research Foundation.

About the University of Pittsburgh Schools of the Health Sciences

The University of Pittsburgh Schools of the Health Sciences include the schools of Medicine, Nursing, Dental Medicine, Pharmacy, Health and Rehabilitation Sciences and the Graduate School of Public Health. The schools serve as the academic partner to the UPMC (University of Pittsburgh Medical Center). Together, their combined mission is to train tomorrow's health care specialists and biomedical scientists, engage in groundbreaking research that will advance understanding of the causes and treatments of disease and participate in the delivery of outstanding patient care. Since 1998, Pitt and its affiliated university faculty have ranked among the top 10 educational institutions in grant support from the National Institutes of Health. For additional information about the Schools of the Health Sciences, please visit http://www.health.pitt.edu.

http://www.upmc.com/media

University of Pittsburgh

Related Science Articles:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.
Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.
Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.
Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.
World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.
PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.
Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.
Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.
More Science News and Science Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.