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Genetic link to sleep and mood disorders

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Scientists identify molecular link between sleep and mood

A poor night’s sleep is enough to put anyone in a bad mood, and although scientists have long suspected a link between mood and sleep, the molecular basis of this connection remained a mystery. Now, new research has found several rare genetic mutations on the same gene that definitively connect the two.

Sleep goes hand-in-hand with mood. People suffering from depression and mania, for example, frequently have altered sleeping patterns, as do those with seasonal affective disorder (SAD). And although no one knows exactly how these changes come about, in SAD sufferers they are influenced by changes in light exposure, the brain’s time-keeping cue. But is mood affecting sleep, is sleep affecting mood, or is there a third factor influencing both? Although a number of tantalizing leads have linked the circadian clock to mood, there is “no definitive factor that proves causality or indicates the direction of the relationship,” says Michael McCarthy, a neurobiologist at the San Diego Veterans’ Affairs Medical Center and the University of California (UC), San Diego.

To see whether they could establish a link between the circadian clock, sleep, and mood, scientists in the new study looked at the genetics of a family that suffers from abnormal sleep patterns and mood disorders, including SAD and something called advanced sleep phase, a condition in which people wake earlier and sleep earlier than normal. The scientists screened the family for mutations in key genes involved in the circadian clock, and identified two rare variants of the PERIOD3 (PER3) gene in members suffering from SAD and advanced sleep phase. “We found a genetic change in people who have both seasonal affective disorder and the morning lark trait” says lead researcher Ying-Hui Fu, a neuroscientist at UC San Francisco. When the team tested for these mutations in DNA samples from the general population, they found that they were extremely rare, appearing in less than 1% of samples.

Fu and her team then created mice that carried the novel genetic variants. These transgenic mice showed an unusual sleep-wake cycle and struggled less when handled by the researchers, a typical sign of depression. They also had lower levels of PER2, a protein involved in circadian rhythms, than unmutated mice, providing a possible molecular explanation for the unusual sleep patterns in the family. Fu says this supports the link between the PER3 mutations and both sleep and mood. “PER3’s role in mood regulation has never been demonstrated directly before,” she says. “Our results indicate that PER3 might function in helping us adjust to seasonal changes,” by modifying the body’s internal clock.

To investigate further, the team studied mice lacking a functional PER3 gene. They found that these mice showed symptoms of SAD, exhibiting more severe depression when the duration of simulated daylight in the laboratory was reduced. Because SAD affects between 2% and 9% of people worldwide, the novel variants can’t explain it fully. But understanding the function of PER3 could yield insights into the molecular basis of a wide range of sleep and mood disorders, Fu says.

Together, these experiments show that the PERIOD3 gene likely plays a key role in regulating the sleep-wake cycle, influencing mood and regulating the relationship between depression and seasonal changes in light availability, the team reports today in the Proceedings of the National Academy of Sciences. “The identification of a mutation in PER3 with such a strong effect on mood is remarkable,” McCarthy says. “It suggests an important role for the circadian clock in determining mood.”

The next step will be to investigate how well these results generalize to other people suffering from mood and sleep disorders. “It will be interesting to see if other rare variants in PER3 are found, or if SAD is consistently observed in other carriers,” McCarthy says. That could eventually lead to new drugs that selectively target the gene, which McCarthy says, “could be a strategy for treating mood or sleep disorders.”

 

http://dx.doi.org:/10.1126/science.aaf4095

 

 

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NIMHD welcomes nine new members to the National Advisory Council on Minority Health and Health Disparities

Reporter: Stephen J. Williams, Ph.D.

The National Institute on Minority Health and Health Disparities (NIMHD) has announced the appointment of nine new members to the National Advisory Council on Minority Health and Health Disparities (NACMHD), NIMHD’s principal advisory board. Members of the council are drawn from the scientific, medical, and lay communities, so they offer diverse perspectives on minority health and health disparities.

The NACMHD, which meets three times a year on the National Institutes of Health campus, Bethesda, Maryland, advises the secretary of Health and Human Services and the directors of NIH and NIMHD on matters related to NIMHD’s mission. The council also conducts the second level of review of grant applications and cooperative agreements for research and training and recommends approval for projects that show promise of making valuable contributions to human knowledge.

The next meeting of the NACMHD will be held on Thursday, Sept. 10, 8:30 a.m.-5:00 p.m. on the NIH campus. The meeting will be available on videocast at http://www.videocast.nih.gov.

NIMHD Director Eliseo J. Pérez-Stable, M.D., is pleased to welcome the following new members

Margarita Alegría, Ph.D., is the director of the Center for Multicultural Mental Health Research at Cambridge Health Alliance and a professor in the department of psychiatry at Harvard Medical School, Boston. She has devoted her career to researching disparities in mental health and substance abuse services, with the goal of improving access to and equity and quality of these services for disadvantaged and minority populations.

Maria Araneta, Ph.D., a perinatal epidemiologist, is a professor in the Department of Family and Preventive Medicine at the University of California, San Diego. Her research interests include maternal/pediatric HIV/AIDS, birth defects, and ethnic health disparities in type 2 diabetes, regional fat distribution, cardiovascular disease, and metabolic abnormalities.

Judith Bradford, Ph.D., is director of the Center for Population Research in LGBT Health and she co-chairs The Fenway Institute, Boston. Dr. Bradford has participated in health research since 1984, working with public health programs and community-based organizations to conduct studies on lesbian, gay, bisexual, and transgender people and racial minority communities and to translate the results into programs to reduce health disparities.

Linda Burhansstipanov, Dr.P.H., has worked in public health since 1971, primarily with Native American issues. She is a nationally recognized educator on cancer prevention, community-based participatory research, navigation programs, cultural competency, evaluation, and other topics. Dr. Burhansstipanov worked with the Anschutz Medical Center Cancer Research Center — now the University of Colorado Cancer Research Center — in Denver for five years before founding Native American Cancer Initiatives, Inc., and the Native American Cancer Research Corporation.

Sandro Galea, M.D., a physician and epidemiologist, is the dean and a professor at the Boston University School of Public Health. Prior to his appointment at Boston University, Dr. Galea served as the Anna Cheskis Gelman and Murray Charles Gelman Professor and chair of the Department of Epidemiology at the Columbia University Mailman School of Public Health, New York City. His research focuses on the causes of brain disorders, particularly common mood and anxiety disorders, and substance abuse.

Linda Greene, J.D., is Evjue Bascom Professor of Law at the University of Wisconsin–Madison Law School. Her teaching and academic scholarship include constitutional law, civil procedure, legislation, civil rights, and sports law. Most recently, she was the vice chancellor for equity, diversity, and inclusion at the University of California, San Diego.

Ross A. Hammond, Ph.D., a senior fellow in the Economic Studies Program at the Brookings Institution, Washington, D.C., is also director of the Center on Social Dynamics and Policy. His primary area of expertise is using mathematical and computational methods from complex systems science to model complex dynamics in economic, social, and public health systems. His current research topics include obesity etiology and prevention, tobacco control, and behavioral epidemiology.

Hilton Hudson, II, M.D., is chief of cardiothoracic surgery at Franciscan Healthcare, Munster, Indiana and a national ambassador for the American Heart Association. He also is the founder of Hilton Publishing, Inc., a national publisher dedicated to producing content on solutions related to health, wellness, and education for people in underserved communities. Dr. Hilton’s book, “The Heart of the Matter: The African American Guide to Heart Disease, Heart Treatment and Heart Wellness” has impacted at-risk patients nationwide.

Brian M. Rivers, Ph.D., M.P.H., currently serves on the research faculty at the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. He is also an assistant professor in the Department of Oncologic Sciences at the University of South Florida College of Medicine, Tampa. Dr. Rivers’ research efforts include examination of unmet educational and psychosocial needs and the development of communication tools, couple-centered interventions, and evidence-based methods to convey complex information to at-risk populations across the cancer continuum.

NIMHD is one of NIH’s 27 Institutes and Centers. It leads scientific research to improve minority health and eliminate health disparities by conducting and supporting research; planning, reviewing, coordinating, and evaluating all minority health and health disparities research at NIH; promoting and supporting the training of a diverse research workforce; translating and disseminating research information; and fostering collaborations and partnerships. For more information about NIMHD, visit http://www.nimhd.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Behavior

Curator: Larry H Bernstein, MD, FCAP

 

Behavior Brief

The Scientist

http://www.the-scientist.com//?articles.view/articleNo/43904/title/Behavior-Brief/

Wasp-directed webs make better cocoons?

Scientists have uncovered more detail about the unique relationship between the parasitic ichneumon wasp (Reclinervellus nielseni) and its arachnid host, the orb-weaving spider (Cyclosa argenteoalba). While the spider carries the wasp’s egg—and later, hatched larva—within its abdomen, the arachnid spins an atypical web, according to a study published last month (August 5) in The Journal of Experimental Biology. When the larva emerges, killing the spider host, the wasp uses the modified webbing to build a cocoon.

“This discovery—of enhanced behavior as opposed to merely switched behavior—is completely new, impressively demonstrated, and rather unexpected I think,” Mark Shaw an entomologist at the National Museum of Scotland, who was not involved in the study, told Newsweek.

According to The Vergescientists from Kobe University in Japan along with their collaborators determined that the modified web is similar to the orb-weaving spider’s resting web that it uses when it molts—only it is 40 times stronger. This may help the wasp larva build a more durable cocoon. Ecologist Sophie Labaude of the University of Burgundy in France, who was not involved in the work told The Verge that the altered web composition may be a coincidental side effect of chemicals thought to be introduced into the spider during the course of the parasitic infection.

Catharus ustulatus with a tracker on its back J. CRAVES

Some songbirds don’t set cruising altitude

A study published last month (August 12) in The Auk: Ornithological Advances reported the first complete flight-altitude data for a songbird, revealing that one species, the Swainson’s thrush (Catharus ustulatus), changes its altitude intermittently throughout its migration.

“I really thought that the birds would mostly behave like commercial aircraft, ascending to a particular altitude, leveling off and cruising near that altitude, and then coming down just before they landed,” study coauthor Melissa Bowlin of the University of Michigan-Dearborn said in a statement. “I was shocked when I made the first graph for the first bird, and thought it was an anomaly. The more data we obtained, however, the more often we saw the up-and-down pattern to the birds’ flight.”

Bowlin and her colleagues attached radio transmitters to nine Swainson’s thrushes captured from a forest in Illinois during the birds’ spring migration seasons between 2011 and 2013. Once the birds took off, the researchers followed them in a car, keeping track of the birds’ altitudes as they flew through different landscapes. The researchers found that the birds often altered their altitudes by more than 100 meters during their migration. While the authors noted that the precise locations at which the birds ascended and descended cannot be determined until more data are analyzed, they speculated that the birds’ decisions to change altitude may be related to atmospheric changes.

“Dr. Bowlin and her colleagues’ unique yet perplexing records of migrant altitudes raise a number of thought-provoking questions that have implications for species conservation,” Robert Diehl of the US Geological Survey’s Northern Rocky Mountain Science Center said in a statement.

FLICKR, LAGGEDONUSER

Bonobos reuse “peeps”

Humans may not be the only species that can disassociate their communication from their environment. Bonobos (Pan paniscus) also seem to produce the same high-pitched “peep” noises to express psychological states regardless of their context or circumstances, according to study published last month (August 4) in PeerJ. This ability, called functional flexibility, is analogous to the cries or laughter of a human infant, the study’s authors wrote.

“When I studied the bonobos in their native setting in the Congo, I was struck by how frequent their peeps were, and how many different contexts they produce them in,” study coauthor Zanna Clay, a psychologist at the University of Birmingham, told The Guardian. “It became apparent we couldn’t always differentiate between peeps. We needed to understand the context to get to the root of their communication.”

Clay and her colleagues recorded bonobo peeps made during a range of situations, including feeding, sleeping, and traveling. The researchers found that peeps produced during positive situations, such as feeding were indistinguishable from those made within neutral contexts such as resting. However, in negative circumstances such as a state of alarm, the bonobos’ peeps were acoustically different.

“We interpret this evidence as an example of an evolutionary early transition away from fixed vocal signaling towards functional flexibility,” Clay told The Guardian.

An ant (Pristomyrmex punctatus) stands guard over a Japanese oakblue caterpillar (Narathura japonica).WIKIMEDIA, L. SHYAMAL

Manipulation or mutalism?

A new study suggests that a species of Japanese ant (Pristomyrmex punctatus) that imbibes the sweet nectar secreted by Japanese oakblue butterfly (Narathura japonica) caterpillars must pay a price. According to a study published this summer (July 28) in Current Biology, chemicals in the nectar can effectively brainwash the ants, turning them into loyal bodyguards for the caterpillars.

An international group of researchers led by investigators at Kobe University found that ants who fed upon N. japonica’s sweet secretion displayed more aggressive behavior and had lower levels of dopamine in their brains than ants found near caterpillars that didn’t consume the nectar, according toScience.

The results suggest that the relationship between the ants and caterpillar may not be mutualistic, as previously thought, but may have an aspect of parasitism.

“It’s possible that these common food-for-defense interactions, which are typically assumed to be mutualistic, may in fact be maintained primarily through parasitic manipulation of ant behavior,” the authors wrote in their report.

NATURE COMMUNICATIONS, J. COSTELLO ET AL.

Young siphonophores take the lead

For physonect siphonophores (Nanomia bijuga), jellyfish-like marine creatures that travel together as a single unit, the youngest colony members alwaysride shotgun, according to a study published yesterday (September 1) in Nature Communications.

To cover distances of up to 200 meters a day to find food, N. bijuga colony members have to work together. “The younger swimming bells at the tip of the colony are responsible for turning. They generate a lot of torque,” study coauthor Kelly Sutherland, an oceanographer at the University of Oregon, said in a statement. “The older swimming bells toward the base of the colony are responsible for thrust.”

Sutherland and her colleagues recorded swimming colonies from Friday Harbor, Washington, and tracked how the organism displaced particles around it to discern the contribution each unit makes to the movement. They found that even small amounts of water displacement exerted by the youngest members at the tip of the colony had big impacts on which direction the unit travelled.

“They are like the handle of a door,” study coauthor John Costello, a biologist at the Marine Biological Laboratory in Woods Hole, Massachusetts, said in a statement. “If you push on a door near its hinges—its axis of rotation—the door is hard to open. But if you push on the door handle, which is far from the axis of rotation, the door opens easily. A little force placed with a big lever arm has a big effect on turning.”

The authors suggested that the siphonophore’s strategy involving multiple propulsion “engines” and efficient directional control could inspire improved designs for underwater vehicles.

Tags

songbirdplanktonparasitismparasitic wasporb web spidernon-human primatesmigration

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