Disrupted Genetic Clocks in Schizophrenia-Affected Brains Reveal Clues to Disease


Rhythms in gene expression in people with schizophrenia, according to a new University of Pittsburgh-led study.

The findings, published today by researchers from 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.

"Said senior author Colleen McClung, Ph.," We are looking for the first time that there are significant disruptions in the daily timing of what is turned out to be, "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 rhythm of different genes, which revealed some interesting patterns.

McClung explained 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 of a schizophrenia affected brain, the lights are on all day and the refrigerator shuts off at night."

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

According to Marianne Seney, Ph.D., Assistant Professor of Psychiatry at the Pitts School of Medicine and the Study of First Sisters 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 did during the day, the control and schizophrenia subjects were not different, but those who died at night, there were major differences, since genes that had gained rhythm their hit low point during the night.

Seney alludes to the analogy of the house. "If we only looked at the refrigerator, it would be no difference, but at night, there would be one."

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.

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