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(Shutterstock)The brain goes through phases over the course of a day, from first awakening to a night’s fatigue.

Two groups of researchers have plunged into those changes, looking for clues to treat mental illness, addiction, problematic aging, and other potential uses. But their work could have untapped potential to a crucial goal in forensic science – pinpointing postmortem interval, or the exact time of death.

The circadian, regular rhythm of brain genes is predictable – but varies with aging of a person, according to an analysis published last month in the Proceedings of the National Academy of Sciences by a University of Pittsburgh School of Medicine team of scientists.

The team analyzed the brains of 146 people whose specific time of death was known. They zoomed in on the prefrontal cortex, and found 235 core genes that make up the “molecular clock” among the thousands of genes at work there. The group of genes showed either expression or inactivity, based on the phase in the daily routine, they said.

They found a unique time signature among the people older than 60. But the nuances of aging and major depression still need to be better researched, they concluded.

“As we expected, younger people had that daily rhythm in all the classic ‘clock’ genes,” said Connie McClung, professor of psychiatry and leader of the Pitt team. “But there was a loss of rhythm of many of these genes in older people, which might explain some of the alterations that occur in sleep, cognition and mood in later life.”

McClung told Forensic Magazine in an interview that forensic applications are still far off - and there could be limitations for homicide detectives. Natural cycles can be thrown into disarray by psychiatric conditions, addiction, or aging - making calculating an exact time of death a moving target at this point in the research.

The work was inspired by prior work from a group of scientists at the Pritzker Consortium, including several from the University of Michigan.

The circadian rhythms of some 89 patients who died suddenly established that more than 100 genes showed 24-hour cyclic patterns, in the Pritzker study, also published in the Proceedings of the National Academy of Sciences, in 2013.

“The phasing of known circadian genes was consistent with data derived from other diurnal mammals,” the team concluded.

The researchers were looking primarily at the disruption in the rhythms which coincided, or even caused, major-depressive disorder among the 34 patients in the group who suffered from the condition.

“Cyclic patterns were much weaker in the brains of patients with (major depressive disorder) due to shifted peak timing and potentially disrupted phase relationships between individual circadian genes.”

Jun Li, professor in the Department of Genetics at Michigan, told Forensic Magazine the potential for forensics is there, especially with the ability to place postmortem interval within one or two hours. But there's a catch: no scientific team is really working on it with that specifically in mind.

"Nobody's trying very hard to apply it that way," said Li. "But in theory, this is possible... Those several hundred genes have a lot of power to tell you time."

Even the theory has caveats, however. If a person has an abnormal rest cycle, possible with a major psychiatric disorder, addiction, or even jet lag, the estimations could be thrown off - like a "broken clock," Li added.

Latest progress on the circadian rhythms was first reported by Carl Zimmer at The New York Times on Dec. 28.

Time of death exactitude is a common goal for multiple disciplines, including certain entomologists, and experts in bacteria, decomposition, and even chemists focusing in on the “smell of death.”

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