Disrupting the brain's internal clock causes depressive-like behavior in mice

November 29, 2016, Elsevier
Credit: Martha Sexton/public domain

Disruptions of daily rhythms of the body's master internal clock cause depression- and anxiety-like behaviors in mice, reports a new study in Biological Psychiatry. The findings provide insight into the role of the brain's internal time keeping system in the development of mood disorders, such as bipolar disorder and major depressive disorder, which have been associated with disturbed daily (circadian) rhythms.

"Our data show that perturbing circadian rhythms in otherwise totally undisturbed animals is enough to cause behaviors similar to human depression," commented first author Dr. Dominic Landgraf of the University of California, San Diego.

Inherent circadian clocks help us function throughout the day, by telling us when to sleep, wake and eat, as well as by synchronizing our bodily processes. "It is perhaps not surprising that disruptions of our natural synchronization can have heavy impacts on our physical and mental health," Dr. Landgraf added.

However, until now researchers did not know if disturbed circadian rhythms were a cause or consequence of . In the new study, a team led by David K. Welsh has shown for the first time a causal relationship between functioning circadian clocks and mood regulation.

The researchers developed a new genetic mouse model by suppressing Bmal1, one of the master genes that drives circadian rhythms, in the suprachiasmatic nucleus (SCN), which serves as the brain's central clock regulator. Diminished Bmal1 expression reduced the strength of the clock signals produced by the SCN by about 80%. Targeting this particular brain region allowed the researchers to focus on the specific effects of the SCN circadian rhythms, and to avoid alterations in other brain regions that have confounded previous studies.

In behavioral tests, mice with reduced circadian rhythms, relative to control mice, were less motivated to escape an uncomfortable situation, which is commonly interpreted as despair or hopelessness in the animal. The mice also showed increased aversion to brightly lit areas, considered to be an indicator of anxiety-like behavior.

In addition to the altered behavior, mice with reduced circadian rhythms gained more weight than normal mice, even though they consumed the same amount of food. This finding suggests that disrupted SCN circadian rhythms could lead to metabolic abnormalities observed in many depressed patients.

Importantly, the findings show that even though the SCN does not directly regulate mood, alterations to circadian rhythms in the SCN are sufficient to cause depression- and anxiety-like behaviors in .

"We have long known that disruptions in circadian rhythms may contribute to depression, particularly in people at risk for major depression or bipolar disorder," said Dr. John Krystal, Editor of Biological Psychiatry. "This new study provides additional evidence implicating the Bmal1 gene in the relationship between these and mood."

According to Dr. Landgraf, the results are an important step toward developing new depression treatments that directly target the in humans.

Explore further: Researchers show how circadian 'clock' may influence cancer pathway

More information: Dominic Landgraf et al. Genetic Disruption of Circadian Rhythms in the Suprachiasmatic Nucleus Causes Helplessness, Behavioral Despair, and Anxiety-like Behavior in Mice, Biological Psychiatry (2016). DOI: 10.1016/j.biopsych.2016.03.1050

Related Stories

Researchers show how circadian 'clock' may influence cancer pathway

November 16, 2016
A new study led by scientists at The Scripps Research Institute (TSRI) describes an unexpected role for proteins involved with our daily "circadian" clocks in influencing cancer growth.

New findings linking abnormalities in circadian rhythms to neurochemical to changes in specific neurotransmitters

May 31, 2016
Results of the first study of its kind to link abnormalities in circadian rhythms to changes in specific neurotransmitters in people with bipolar disorder will be published this week in the journal Biological Psychiatry.

Exercise combined with methamphetamine regimen could be a powerful new way to treat addiction

October 13, 2016
Exercise coupled with a regimen of methamphetamine could help addicts get clean, according to a pre-clinical study published today in the FASEB Journal. The reason lies in the mechanism through which exercise and methamphetamine ...

Biological clocks orchestrate behavioral rhythms by sending signals downstream

February 29, 2016
Different groups of neurons program biological clocks to orchestrate our behaviors by sending messages in a unidirectional manner downstream, a team of biologists has found.

Neuroscientists identify cell type in the brain that controls body clock circadian rhythms

March 17, 2015
UT Southwestern Medical Center neuroscientists have identified key cells within the brain that are critical for determining circadian rhythms, the 24-hour processes that control sleep and wake cycles, as well as other important ...

Recommended for you

Looking for the origins of schizophrenia

February 23, 2018
Schizophrenia may be related to neurodevelopmental changes, including brain's inability to generate an appropriate vascular system, according to new study resulted from a partnership between the D"Or Institute for Research ...

Color of judo uniform has no effect on winning

February 22, 2018
New research on competitive judo data finds a winning bias for the athlete who is first called, regardless of the colour of their uniform. This unique study, published in Frontiers in Psychology, puts to rest the debate on ...

Infants are able to learn abstract rules visually

February 22, 2018
Three-month-old babies cannot sit up or roll over, yet they are already capable of learning patterns from simply looking at the world around them, according to a recent Northwestern University study published in PLOS One.

Antidepressants are more effective than placebo at treating acute depression in adults, concludes study

February 22, 2018
Meta-analysis of 522 trials includes the largest amount of unpublished data to date, and finds that antidepressants are more effective than placebo for short-term treatment of acute depression in adults.

How people cope with difficult life events fuels development of wisdom, study finds

February 21, 2018
How a person responds to a difficult life event such as a death or divorce helps shape the development of their wisdom over time, a new study from Oregon State University suggests.

Smartphones are bad for some teens, not all

February 21, 2018
Is the next generation better or worse off because of smartphones? The answer is complex and research shows it largely depends on their lives offline.

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.