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Body clock genes linked to depression

20 May 2013

By Dr Amina Aitsi-Selmi

Appeared in BioNews 705

Genes believed to regulate sleep rhythm are expressed abnormally in people with major depressive disorders, scientists say. The study is one of the first in humans to provide direct evidence of a disturbed circadian rhythm in people with depression.

Symptoms of depression can include sleep disturbance, with difficulties in falling asleep at night or feeling fatigued during the day, but the precise mechanism for this remains unknown. Although the circadian rhythm – the 24-hour cycle in living beings – has been observed in gene expression in animal studies, its presence in the human brain has been difficult to confirm.

The study by researchers at the University of Michigan and other US institutions examined tissue taken from 55 'healthy' donated brains post-mortem and compared them with samples from 35 patients who had had a major depressive disorder. The researchers measured the genes thought to be associated with the body's circadian rhythm using DNA microarray analysis and found that in the 'normal' samples the cyclic gene expression in more than 100 genes across six different regions in the brain was consistent with observations in animal studies. Many of the genes showing a 24-hour cycle in these samples were genes known to be associated with the circadian rhythm, confirming the range of genes involved in regulating the body's internal clock.

'Hundreds of new genes that are very sensitive to circadian rhythms emerged from this research - not just the primary clock genes that have been studied in animals or cell cultures, but other genes whose activity rises and falls throughout the day', said Dr Huda Akil, one of the senior authors of the study, co-director of the University of Michigan's Molecular and Behavioural Neuroscience Institute and co-director of the UM site of the Pritzker Neuropsychiatric Disorders Research Consortium, which supported the research.

However, the specimens taken from patients with depression showed a weaker and disrupted gene expression. The gene expression for the active hours would resemble a nocturnal pattern, while at night would often look like a day pattern. 'It's as if they were living in a different time zone than the one they died in', said lead author Dr Jun Li at the Department of Human Genetics, University of Michigan.

The researchers also explained the pattern of gene activity in the daytime was so distinctive that they were able to estimate the time of day each donor had died. 'We were truly able to watch the daily rhythm play out in a symphony of biological activity, by studying where the clock had stopped at the time of death. And then, in depressed people, we could see how this was disrupted', said Dr Akil.

The researchers said that the findings add to the growing understanding of the biological causes of depression, but the sample size was small, with only 55 patients used to identify the 'normal' pattern of gene expression. The authors also point out that drug treatment and the depression itself may have caused the findings. 'The disruption [of circadian rhythm] seen in depression may have more than one cause', Dr Akil said.


27 February 2017 - by Emma Laycock 
Researchers have found a set of bodyclock-controlled genes that activate in later life and times of intense stress to protect the body...
13 February 2017 - by Ayala Ochert 
Miscarriage rates following IVF appear to increase when the clocks go forward in the spring, according to a study...
08 August 2016 - by Helen Robertson 
Scientists have identified 17 genetic variants that appear to be linked to depression in individuals with European ancestry...
08 February 2016 - by Dr Barbara Kramarz 
Scientists have used data from personal genomics company 23andMe to identify a set of genes that are linked to being a 'morning person'...
27 July 2015 - by Ayala Ochert 
A study mimicking the effects of shift work has found that just one night without sleep alters the expression of bodyclock genes and disrupts metabolism...

07 May 2013 - by Cristy Gelling 
Genetic mutations that cause an inherited sleep disorder also appear to be linked to migraine, scientists have found...
20 August 2012 - by Maren Urner 
Researchers at Yale University in the USA may have found an explanation for why patients with severe depression often show a decreased brain volume in certain areas of the brain...
20 February 2012 - by Oliver Timmis 
What time of day it is could influence whether or not we get an infection. A protein known to be involved in the immune system may be influenced by the body's circadian rhythm, according to researchers at Yale University...
16 November 2009 - by Gozde Zorlu 
A new study has linked a gene implicated in regulating how much sleep a child needs to bipolar disorder in children. Variations in a gene called RORB, which is known to affect sleeping patterns through disrupting the regulation of the body's internal 'circadian' rhythm, are likely more common among children with bipolar disorder, according to research published online in the journal BMC Psychiatry. But more research is needed to validate the findings, said the researchers....

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