News From The Journal Of Clinical Investigation Online Early March 3, 2008

Role for the serotonin transporter in platelet aggregation



New data, generated by Randy Blakely and colleagues, at Vanderbilt University, Nashville, have established a role for constitutive expression of the protein SERT (the serotonin transporter) in platelet aggregation, a key event in blood clotting. In the study, SERT expression and function were shown to have a role in the aggregation of both mouse and human platelets. Mechanistically, SERT was found to interact directly with the beta-3 component of a protein known as integrin alpha-IIb/beta-3, and this led to increased SERT expression on the surface of the platelet and thereby increased SERT function. Alterations in SERT distribution in platelets was linked to polymorphisms in the beta-3 gene. The interaction of the genes that make beta-3 and SERT has been of substantial clinical interest as they have been implicated in cardiovascular disease and autism. The authors therefore suggested that the demonstration that SERT interacts with integrin beta-3 provides a possible mechanistic basis for these recent genetic associations. In addition, as SERT is the target for the most widely prescribed class of antidepressants (SSRIs), the authors suggest that these data might help explain the recognized comorbidities between cardiovascular disease and depression.



TITLE: Interactions between integrin alpha-IIb/beta-3 and the serotonin transporter regulate serotonin transport and platelet aggregation in mice and humans



AUTHOR CONTACT:

Randy D. Blakely

Vanderbilt University School of Medicine, Nashville, Tennessee, USA.



Seeing clearly how genetic mutations cause loss of sight



Retinitis pigmentosa (RP) is a hereditary disease that often results in complete loss of sight as a result of the progressive degeneration of the retina of the eye. Mutations in many different genes are known to cause RP, one of which is PRPF31. New data generated by Carlo Rivolta and colleagues at the University of Lausanne, Switzerland, have provided insight into the effect of several different RP-causing PRPF31 mutations.



The information in genes is translated into protein via an mRNA intermediate. In the study, six different PRPF31 mutations that cause RP were found to generate substantially less mRNA, and therefore dramatically lower amounts of protein, than nonmutated PRPF31. Surprisingly, although blocking a process known as nonsense-mediated mRNA decay, which destroys certain forms of mRNA that would not correctly translate the information in a gene into protein, increased the amount of mRNA generated from the mutated PRPF31, no increase in mutant protein was observed. The authors therefore suggested that most PRPF31 mutations are effectively nonfunctional because surveillance mechanisms destroy any mRNA generated from the mutated genes, and therefore that PRPF31 mutations mediate their RP-causing effect by decreasing the amount of PRPF31 protein present in a cell.
















TITLE: Premature termination codons in PRPF31 cause retinitis pigmentosa via haploinsufficiency due to nonsense-mediated mRNA decay



AUTHOR CONTACT:

Carlo Rivolta

University of Lausanne, Lausanne, Switzerland.


Why muscle wasting diseases may not require stem cell treatment after all



Muscle wasting, also known as muscle atrophy, can be caused by inactivity, injury, disease, aging, and medication. Many studies have shown that muscle atrophy is accompanied by death of the DNA-containing myonuclei of muscle fibers, which would mean that recovery from muscle atrophy would require replenishment from muscle stem cells. In a new study, Jo Bruusgaard and Kristian Gundersen at the University of Oslo, Norway, used time-lapse microscopy of mouse muscle fibers and myonuclei during atrophy to investigate this process. When mice were subjected to muscle atrophy by various methods, physical evidence of wasting was apparent by significantly decreased muscle fiber areas. However, myonuclei death was not observed in any case during the 28 days of monitoring. The authors concluded therefore that intervention efforts to reverse muscle atrophy should not focus on muscle stem cells.



TITLE: In vivo time-lapse microscopy reveals no loss of murine myonuclei during weeks of muscle atrophy



AUTHOR CONTACT:

Kristian Gundersen

University of Oslo, Oslo, Norway.


Learning more about why people with Bardet-Biedl syndrome are obese



Bardet-Biedl syndrome (BBS) is a genetic disorder characterized by many features, including obesity and an increased risk of heart disease. Although BBS is a rare disorder, because it is characterized by problems faced by an increasing number of individuals who do not have BBS, much effort is being invested in determining the genes that are mutated in individuals with BBS and how these contribute to obesity and increased risk of heart disease. New data generated by Kamal Rahmouni and colleagues at the University of Iowa Carver College of Medicine, Iowa City, have indicated that sensitivity to the hormone leptin, which suppresses appetite and increases energy expenditure by activating leptin receptors on specific nerves in the brain, is lost in three mouse models of BBS.



In the study, administration of leptin to mice lacking Bbs2, Bbs4, or Bbs6 (proteins made by three of the twelve genes so far identified as being mutated in individuals with BBS) was found to have little effect on body weight and food intake. Further analysis indicated that this resistance to the effects of leptin as an appetite suppressor was associated with a defect in nerves in the brain known as proopiomelanocortin neurons. Although all three strains of mice were resistant to the effects of leptin as an appetite suppressor, only Bbs2-/- mice were resistant to the effects of leptin on arterial blood pressure. As such, Bbs2-/-" mice had normal blood pressure, whereas Bbs4-/- mice and Bbs6-/- mice had elevated blood pressure. These data have provided insight into why individuals who have BBS as a result of different genetic mutations might exhibit different clinical symptoms.



TITLE: Leptin resistance contributes to obesity and hypertension in mouse models of Bardet-Biedel syndrome



AUTHOR CONTACT:

Kamal Rahmouni

University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.


Eradicating established tumors in mice



Although an immune response mediated by T cells is mounted toward a tumor, over time the tumor adapts and can escape control by the immune response. Similar problems are an obstacle to T cell-based immunotherapeutic approaches to treating individuals with cancer. Loss of the target of the T cells is one mechanism by which tumors escape immune control. A new study by Bin Zhang and colleagues, at the University of Chicago, has characterized immune pathways that can eradicate established tumors in mice, including variants of the tumor that had lost the target of the antitumor T cells (so called antigen-loss-variants; ALVs). Specifically, in this model, the production of the soluble factors IFN-gamma and TNF by antitumor cytotoxic T cells was required for tumor eradication. For these soluble factors to mediate their antitumor effects both bone marrow and stromal cells had to express IFN-gamma and TNF receptors. These data led the authors to suggest that IFN-gamma and TNF acted on tumor stroma to effect bystander killing of ALVs, and they hope that this insight will aid in the development of effective strategies to eliminate established cancers.



TITLE: IFN-gamma - and TNF-dependent bystander eradication of antigen-loss variants in established mouse cancers



AUTHOR CONTACT:

Bin Zhang
University of Texas Health Science Center, San Antonio, Texas, USA.


Learning from a new model for potassium-induced muscle weakness



HyperKPP is a genetic muscle disorder that causes muscle weakness in response to resting after strenuous exercise and to eating potassium-rich foods, among other things. To better understand the mechanisms underlying HyperKPP, Lawrence Hayward and colleagues at the University of Massachusetts Medical School in Worcester, generated a mouse model of the disease by introducing a genetic mutation that causes HyperKPP into the corresponding mouse gene. These mice developed problems similar to individuals with HyperKPP, including abnormally slow muscle relaxation, muscle weakness following potassium exposure at levels typical in human muscle fibers during exercise, and slow recovery from muscle fatigue. The authors therefore hope that this mouse model of HyperKPP may help researchers better understand the human disease and develop better therapies for it and related disorders.



TITLE: Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness



AUTHOR CONTACT:

Lawrence J. Hayward
University of Massachusetts Medical School, Worcester, Massachusetts, USA.






Contact: Karen Honey


Journal of Clinical Investigation

Chr. Hansen And CLC Bio In 1.8M USD Research Project On Identifying Bacteria Genes

Chr. Hansen has teamed up with CLC bio and Roskilde University in an effort understand the genetic make-up of bacteria and see whether this knowledge can be used to improve probiotic food products. New bioinformatics solutions will make it possible to further understand why bacteria perform the way they do, and to find undiscovered potential in lactic acid bacteria. This could in time lead to improved probiotic food products, like fermented milk, and dietary supplements for the global consumers.


Group leader of Genomics at Chr. Hansen, Dr. Martin B. Pedersen, states,
We are proud to be part of this project with CLC bio which gives us access to state-of-the-art bioinformatics methods, and we hope new more advanced methods will be developed within the 4-year duration of the project. It will help us to better understand and develop our probiotic strains for future products with beneficial effect on human health.


During the project, Chr. Hansen, CLC bio, and Roskilde University will work in conjunction with researchers in Aalborg and Copenhagen in Denmark, and Tokyo in Japan. The scientists will use bioinformatics, a way of converting complex biological data such as DNA into practical knowledge using complicated mathematical models and statistics, to analyze the bacteria.


The project has a total budget of 1.8 million USD of which half will be provided by the Danish Strategic Research Council.


Chr. Hansen develops natural ingredient solutions such as cultures, enzymes, colors and flavors. The ingredients are used in the food, pharmaceutical, nutritional and agricultural industries.


About CLC bio


CLC bio is the world's leading full-service bioinformatics solution provider, solely focusing on the development of bioinformatics: software, hardware, data analysis, and custom-designed bioinformatics algorithms. CLC bio is an Apple solution provider and value added reseller.


CLC bio's mission is to be among the most innovative bioinformatics companies in the 21st century. This is realized through:


-- Development of bioinformatics software and hardware based on the latest scientific findings

-- User-friendly, integrated and intuitive software solutions

-- Continuous focus on customer needs and superior customer service

-- Frequent product updates including the latest IT technologies and bioinformatics algorithms

-- A flexible IT architecture, enabling customers to buy or develop individualized solutions at a reasonable price.


clcbio

Discovery Of A New Function Of The Prion Protein Improves Our Understanding Of Epilepsy

Cellular prion protein (PrPc) plays an essential role in maintaining neurotransmitter homeostasis in the central nervous system. This discovery has been made possible by the observation that both a deficiency and an excess of the protein have a considerable effect on this homeostasis. Surprisingly, in both cases, the central nervous excitability threshold is altered to such an extent that an epileptic seizure may result. Thanks to this discovery, we now have more tools at our disposal that can help us to deepen our basic understanding of epilepsy.


The discovery, carried out by researchers of the Institute for Bioengineering of Catalonia (IBEC) and the University of Barcelona (UB), led by Jos?© Antonio Del R?­o, with the collaboration of researchers at Pablo de Olavide University and the National Institute for Food and Agriculture Technology Research, was presented in a study published in PLoS ONE.


Neurotransmitter homeostasis is achieved through a balance between those mechanisms that excite the neurons of the central nervous system and those that inhibit them. In the study, it was observed in laboratory animals that when PrPc is absent, the excitatory mechanisms are altered and epileptic seizures may occur. As under normal conditions the protein is found in adequate concentrations, it was expected that greater amounts of PrPc would provide greater protection against seizures.. Surprisingly, however, the study showed that this is not the case. With an excessive amount of the protein, the level of excitability of the central nervous system is increased even more than in the absence of PrPc, due to the fact that both the excitatory and inhibitory mechanisms are altered. Such alterations further increase the possibility of suffering severe epileptic seizures. These results allow us to conclude that the protein, when present at adequate concentrations, is essential for maintaining neurotransmitter homeostasis or equilibrium in the central nervous system.


The researchers of IBEC and the UB who participated in the study are currently involved in developing a description of the possible differences in the expression and modification of the cellular prion protein in epileptic patients.


Gene Regulation


The study published in PLoS ONE also found a correlation between the differential susceptibility induced by alterations in PrPc levels and the gene expression of the excitatory and inhibitory neurotransmitter receptors of the cerebral cortex. It was conducted using transcriptomic microarray analysis, which made it possible to identify a set of 129 co-regulated genes in the absence and overexpression of the protein in the brains of laboratory animals. The analysis of the canonical pathways associated with these co-regulated genes and its subsequent validation made it possible for the first time to determine that both the absence and the overexpression of PrPc affect the levels of expression of glutamate receptors (AMPA-Kainate an excitatory neurotransmitter) and of GABA (GABAA an inhibitory neurotransmitter). Finally, the effects of the differential regulation were corroborated by electrophysiological techniques that are pioneering in Spain.


Source: Institute for Bioengineering of Catalonia

Link Between Antidepressants And Suicidality In Teens? Carnegie Mellon, Ohio State Get Grant For Study

An interdisciplinary team of researchers from Carnegie Mellon University and The Ohio State University has received a five-year, $1.2 million grant from the National Institute of Mental Health to investigate the link between antidepressants and suicidality -- including suicidal thoughts, attempts and suicide deaths. The researchers have previously challenged the U.S. Food and Drug Administration's (FDA) findings that antidepressants are causally linked to an increase in suicidal thoughts and behaviors in young people.



In 2004, the FDA performed a meta-analysis of the results of randomized clinical trials of antidepressants and concluded that the drugs led to increased suicidal behaviors and thoughts, which it termed "suicidality," among children and adolescents. As a result, the FDA required manufacturers to place a black box warning on the labels of antidepressants -- the strongest regulatory action the agency can take short of an outright ban. This has led to a decline in prescriptions of antidepressants for children and adolescents.



But the results of a study published in April by scientists from Carnegie Mellon and Ohio State suggest that the FDA may have overstated the actual risk to most teens and children on antidepressants. Using sophisticated statistical techniques, the researchers found an increased risk of suicidality only among adolescents who suffered from major depressive disorder, and then only among those who took a specific class of antidepressants -- selective serotonin reuptake inhibitors (SSRIs). Antidepressants are prescribed for a variety of other psychological ailments, such as obsessive-compulsive disorder and general anxiety disorder.



"Our concern was that by mixing together different diagnostic groups as well as different formulations of antidepressants, the FDA was underestimating important sources of variability that would make their results look more significant than they were," said Joel Greenhouse, professor of statistics at Carnegie Mellon and one of the study's authors.



Working with Greenhouse will be Howard Seltman, a research scientist in Carnegie Mellon's Statistics Department; Eloise Kaizar, who recently earned her Ph.D. in statistics from Carnegie Mellon and soon will join the statistics faculty at Ohio State; and Kelly Kelleher, director of the Center for Innovation in Pediatric Practice and vice president for Health Services Research in the Columbus Children's Research Institute at Columbus Children's Hospital. Kelleher is also a faculty member of Ohio State's College of Medicine.



Greenhouse said several other factors are worth noting. The clinical trials that formed the basis of the FDA's review were not designed to measure suicide; their purpose was to determine the efficacy of various antidepressants in treating mental illness among children and adolescents. None of the approximately 4,600 youth who participated in those studies committed suicide, and the number of suicide attempts was too low to be statistically significant. That prompted the FDA to broaden its primary outcome to include suicidality, even though there is no evidence of a link between suicidality and suicide itself.



The researchers will use the grant to analyze other data sources that might shed light on what relationship, if any, antidepressant use has with suicidal behavior. For example, the FDA did not take into account recent results from large observational studies that, using health administrative data, have been unable to find an increased risk of suicidal behavior among youths who use antidepressants. They will also review psychotherapy studies to see whether there is an increase in suicidality among teens who were successfully treated with methods other than antidepressants. Greenhouse said that many psychiatrists believe that as their patients' conditions improve, they are more likely to express suicidal thoughts simply because they are better able to articulate their feelings.



"As a regulatory agency, the FDA made a public health decision to issue the black box warning. From a scientific perspective, we are interested in the question, 'What evidence, if any, is out there that would convince the FDA to remove the black box warning?' We want to do this systematically and look at alternative explanations as well," Greenhouse said.





Contact: Jonathan Potts


Carnegie Mellon University

More Complete View Of Breast Cancer Gene Mutations In US Population: New Findings

A large study funded by the National Institutes of Health today provided the clearest picture yet of the prevalence in the U.S. population of mutations in two genes associated with an increased risk of breast cancer. The genes are called Breast Cancer 1 (BRCA1) and Breast Cancer 2 (BRCA2). In addition, the study identified key predictors for assessing which women are most likely to carry these genetic mutations.



Each year, approximately 200,000 women in the United States are diagnosed with breast cancer. The majority of breast cancer cases are caused by genetic changes that occur during a woman's lifetime and not by genetic mutations inherited from her parents. However, researchers estimate that inherited mutations play a role in anywhere from 5 to 27 percent of all breast cancer cases. In the mid 1990s, researchers found that mutations in the BRCA1 and BRCA2 genes are a major cause of the hereditary form of the disease. Women inheriting these mutations have a 40 to 85 percent lifetime risk of developing breast cancer, as well as an increased risk of ovarian cancer.



To date, most of the studies on BRCA1 and BRCA2 mutations have focused on families known to be at high risk for breast cancer and on women who develop breast cancer at a relatively young age. The new study, published today in the journal Cancer Research, looked at the prevalence and predictors of BRCA1 and BRCA2 mutations in under-studied groups of women, such as African Americans and older women.



"Studies of any notable size have focused almost exclusively on white women and young women. This research clearly was needed to improve our means of assessing the likelihood of carrying BRCA1 and BRCA2 mutations in a wider spectrum of women," said one of the study's lead investigators, Elaine Ostrander, Ph.D., chief of the Cancer Genetics Branch in the National Human Genome Research Institute's Division of Intramural Research. Dr. Ostrander was previously head of the genetics program at the Fred Hutchinson Cancer Research Center, which is the institution that led the study.



The researchers examined the prevalence and predictors of BRCA1 and BRCA2 mutations in 1,628 women with breast cancer and 674 similar women without breast cancer, all of whom were participants in the National Institute of Child Health and Human Development's (NICHD's) Women's Contraceptive And Reproductive Experiences (CARE) study. The women involved in the study were white and African American women, ages 35 to 64, who lived in the Atlanta, Detroit, Los Angeles, Philadelphia and Seattle metropolitan areas.



"The advantages of this study include its large sample size, inclusion of under-studied groups of women and the fact that the results are population based," said one of the study's co-authors, Robert Spirtas, Dr.P.H, former chief of NICHD's Contraception and Reproductive Health Branch and now retired.
















Researchers found that 2.4 percent of the breast cancer patients had BRCA1 mutations and 2.3 percent had BRCA2 mutations. BRCA1 mutations were more common among white breast cancer patients (2.9 percent) than among African American patients (1.4 percent). Breast cancer patients of Jewish ancestry were also significantly more likely to have BRCA1 mutations than non-Jewish patients - 10.2 percent compared to 2.0 percent. For BRCA2, African American patients were slightly more likely to have mutations, 2.6 percent, than were white patients, 2.1 percent.



Based on their findings, the researchers went on to calculate the prevalence of BRCA1 and BRCA2 mutations in the general U.S. population. Among white and African American women ages 35 to 64, the prevalence of BRCA1 mutations is 0.06 percent and the prevalence of BRCA2 mutations is 0.4 percent, the researchers estimated.



"These findings from our large, population-based study are compatible with earlier estimates made by extrapolating from smaller studies. However, we found a slightly lower frequency of BRCA1 mutations and a higher frequency of BRCA2 mutations," said the study's other lead investigator, Kathleen Malone, Ph.D., Member of the Public Health Sciences Division at the Fred Hutchinson Cancer Center. "We think the difference lies in the fact that earlier studies were confined mainly to whites, and that African American women carry BRCA2 mutations more often than white women."



The researchers also identified key predictors of whether a woman with breast cancer is likely to carry a BRCA1 or BRCA2 mutation. Such information is important because it can help to improve means of assessing which women may benefit the most from genetic testing, increased breast cancer screening and other measures aimed at early detection, treatment or prevention. The most significant predictors for BRCA1 mutations were: Jewish ancestry, a family history of ovarian cancer and a family history of breast cancer occurring before age 45.



For BRCA2 mutations, researchers uncovered fewer predictors, and they had more modest effects. Among the breast cancer patients studied, the only significant predictors of a BRCA2 mutation were early age of onset (before age 45) in the patient herself or early onset of breast cancer in mother, sisters, grandmothers or aunts.



"These findings underscore why women need to learn as much as they can about their family health history and then share that information with their health-care professionals. However, it must be emphasized that the presence or absence of a predictive factor does not automatically equate with a high or low likelihood of carrying a breast cancer gene mutation," said NIH Director Elias A. Zerhouni, M.D. "The majority of women with breast cancer - even those with a family history of the disease - do not carry mutations in these genes. These predictors need to be considered in the context of each woman's complete family health history."







In addition to the Fred Hutchinson Cancer Center, NHGRI and NICHD, the team included researchers from the National Cancer Institute; Bay State Medical Center, Springfield, Mass.; the University of Pennsylvania, Philadelphia; University of Southern California, Los Angeles; and Wayne State University, Detroit.



About NIH

The National Cancer Institute, the National Institute of Child Health and Human Development, and the National Human Genome Research Institute are among the 27 institutes and centers that make up the National Institutes of Health (NIH) - The Nation's Medical Research Agency. NIH is a component of the U. S. Department of Health and Human Services (HHS). It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.



How to Create a Family Health History

To help people in the task of creating their family health histories, HHS offers a free, computerized tool that organizes health information into a printout that can be can taken to health-care professionals. The tool, called "My Family Health Portrait," is available at https://familyhistory.hhs/.



Contact: Geoff Spencer


NIH/National Human Genome Research Institute

Discovery Of Mechanism For Postpartum Depression In Mice May Lead To Better Treatments

Researchers have pinpointed a mechanism in the brains of mice that could explain why some human mothers become depressed following childbirth. The discovery could lead to improved treatment for postpartum depression. Supported in part by the National Institute of Mental Health, of the National Institutes of Health, the study used genetically engineered mice lacking a protein critical for adapting to the sex hormone fluctuations of pregnancy and the postpartum period.



"For the first time, we may have a highly useful model of postpartum depression," said NIMH Director Thomas R. Insel, M.D. "The new research also points to a specific potential new target in the brain for medications to treat this disorder that affects 15 percent of women after they give birth."



"After giving birth, female mice deficient in the suspect protein showed depression-like behaviors and neglected their newborn pups," explained Istvan Mody, Ph.D., of the University of California at Los Angeles, who led the research. "Giving a drug that restored the protein's function improved maternal behavior and reduced pup mortality."



Mody and Jamie Maguire, Ph.D., report on their findings in the July 31, 2008 issue of Neuron.



Researchers had suspected that postpartum depression stemmed from the marked fluctuations in estrogen and progesterone that accompany pregnancy and childbirth. Yet manipulating the hormones experimentally triggers depression only in women with a history of the disorder. The roots of their vulnerability remain a mystery.



Evidence suggested that the hormones exert their effects on mood through the brain's major inhibitory chemical messenger system, called GABA, which dampens neural activity, helping to regulate when a neuron fires.



Mody and Maguire discovered that a GABA receptor subunit fluctuated conspicuously during pregnancy and postpartum in the brains of female mice, hinting that it might have pivotal behavioral effects. To find out, they used mice lacking the gene for this subunit and studied them in situations that can elicit responses similar to human depression and anxiety.



Much like human mothers suffering from postpartum depression, the genetically altered mouse mothers were more lethargic and less pleasure-seeking than normal mice. They also shunned their pups and failed to make proper nests for them.



This abnormal maternal behavior was reversed and pup survival increased after the researchers gave the animals a drug called THIP that acts on the receptor in a way that specifically restores its function in spite of the reduced number of subunits.



"Improper functioning of the subunit could impair the GABA system's ability to adapt to hormone fluctuations during the highly vulnerable post partum period," explained Maguire. "Targeting this subunit might be a promising strategy in developing new treatments for postpartum depression."







Reference:



Maguire J, Mody I. GABAAR plasticity during pregnancy: relevance to postpartum depression. Neuron. 2008 Jul 31;



The National Institute of Mental Health (NIMH) mission is to reduce the burden of mental and behavioral disorders through research on mind, brain, and behavior. More information is available at the NIMH website, nimh.nih/.



The National Institutes of Health (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. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.

Panic Attacks Are Linked To Poor Outcomes For Diabetic Patients, Group Health Study Finds

There is a strong link between panic episodes and increased complications from diabetes, according to a study conducted at Group Health Cooperative, a Seattle-based nonprofit health care system that coordinates care and coverage. The work appears in the November issue of General Hospital Psychiatry.



The researchers surveyed patients with diabetes about their symptoms, disability, social and emotional function, and quality of life. They also collected data on the patients' blood sugar levels, diabetic complications, and other illnesses.



The team had previously reported a strong link between diabetes and depression, which often goes along with panic disorders. They were interested in examining panic independently, however, to see whether patients who have panic without depression would also have poor diabetic outcomes.



"Panic attacks can mimic episodes of hypoglycemia (low blood sugar), so we need a better understanding of how the two conditions are related," explained Evette Ludman, PhD, lead author of the article and a research associate at Group Health. "We don't want people adjusting their blood sugar thinking they are having hypoglycemia when their symptoms are actually caused by a panic disorder."



Of the 4,385 patients surveyed, 193 reported experiencing recent episodes of panic or fear that caused them to change their immediate behavior. After accounting for the effect of depression, panic episodes were associated with higher blood sugar levels, increased diabetic complications and symptoms, greater disability, and lower self-rated health and functioning.



About half of the patients with panic also reported having major depression. By contrast, only 10 percent of patients without panic episodes had major depression.


Panic episodes may be a consequence of the diabetes itself, the researchers explain. Also, panic may interfere with patients' self-care and ability to follow their treatment plans.



If you have diabetes and you know that anxiety is an issue for you, you should talk to your doctor about possible treatment for your anxiety," advised Ludman. And doctors should carefully assess their patients with diabetes, looking for signs of depression or panic disorders, she added.






The study was funded by the National Institute of Mental Health.



About Group Health Center for Health Studies



Founded in 1947, Group Health is Seattle-based, consumer-governed, nonprofit health care system that coordinates care and coverage. The Group Health Center for Health Studies conducts research related to prevention, diagnosis, and treatment of major health problems. It is funded primarily through government and private research grants.



Contact: Joan DeClaire


Group Health Cooperative Center for Health Studies

Surplus Of Serotonin Receptors May Explain Failure Of Antidepressants In Some Patients

An excess of one type of serotonin receptor in the center of the brain may explain why antidepressants fail to relieve symptoms of depression for 50 percent of patients, a new study from researchers at Columbia University Medical Center shows.


The study is the first to find a causal link between receptor number and antidepressant treatment and may lead to more personalized treatment for depression, including treatments for patients who do not respond to antidepressants and ways to identify these patients before they undergo costly, and ultimately, futile therapies.


The research, led by Rene Hen, PhD, professor of pharmacology in the Departments of Psychiatry and Neuroscience at Columbia University, and a researcher the New York State Psychiatric Institute, appears in the January 15 issue of the journal Neuron.


Most antidepressants - including the popular SSRIs - work by increasing the amount of serotonin made by cells -- called raphe neurons -- deep in the middle of the brain. Serotonin relieves symptoms of depression when it is shipped to other brain regions.


But too many serotonin receptors of the 1A type on the raphe neurons sets up a negative feedback loop that reduces the production of serotonin, Dr. Hen and his colleagues discovered


"The more antidepressants try to increase serotonin production, the less serotonin the neurons actually produce, and behavior in mice does not change," Dr. Hen says.


Dr. Hen and his colleagues measured the effect of antidepressants with a commonly used behavioral test that measures the boldness in mice when retrieving food from bright open areas. Mice on antidepressants usually become more daring, but the drugs had no such effect on mice with surplus serotonin receptors.


Recent genetic and imaging studies of depressed patients have suggested that high receptor numbers of the 1A type in the raphe neurons are associated with treatment failure. Until now, no direct test of the association could be performed because the number of receptors in the raphe neurons could not be altered without changing the number of receptors in other parts of the brain.



Using new techniques in genetic engineering, Dr. Hen created a strain of mouse that can be programmed to produce high or low levels of serotonin receptors of the 1A type only in the raphe neuron. The levels present in the mice mimicked the levels found in people who are resistant to antidepressant treatment.


"By simply tweaking the number of receptors down, we were able to transform a non-responder into a responder," Dr. Hen adds.


That strategy also may work for patients resistant to antidepressant treatment, Dr. Hen says, if drugs can be found to reduce the number of receptors or impede their activity.


But first the role of surplus serotonin receptors in people must be confirmed. Dr. Hen's lab is now looking at patients enrolled in clinical trials to see if receptor levels predict response to antidepressants.


Authors of the Neuron study are Jesse W. Richardson-Jones, Caryne P. Craige, Bruno P. Guiard, Alisson Stephen, Kayla L. Metzger, Hank F. Kung, Alain M. Gardier, Alex Dranovsky, Denis J. David, Sheryl G. Beck, Rene Hen and E. David Leonardo.


This study was supported in part by NIMH, NARSAD and AstraZeneca.


Source

Columbia Psychiatry

Columbia University Medical Center

Seeking A Vaccine For Helicobacter pylori In Chilean Patients

Helicobacter pylori (H. pylori) is the causal agent of chronic gastritis, ulcer and gastric cancer. It has the potential to persist in the human stomach for decades, sometimes causing neither harm nor clinical symptoms. Nevertheless, on some occasions, depending on the host immune system and the strain causing the infection, the outcome can be very serious. To maintain the infection, the bacterium must adapt to survive the host defences. One way to accomplish this is to sequentially change the external proteins on the bacterial surface.



A research article published in the World Journal of Gastroenterology addresses this. As part of a search for adequate antigens to generate a vaccine against H. pylori, a group lead by Dr. Alejandro Venegas studied 2 potential targets, HopE and HopV outer membrane proteins, which function as porins. The study revealed that out of 130 H. pylori strains, 60 and 82 of them possessed the hopE and hopV genes, respectively, but only 16 and 9 actually expressed them and synthesized the respective proteins. In other words, 73% and 90% of the hopE and hopV detected genes were turned off. In addition, roughly 10% of H. pylori-infected patients develop immunoreactivity against HopV or HopE, which confirms the low number of strains expressing them. These proteins are part of a larger family, with which they share sequence homology, so their genes are redundant. These genes could be turned alternatively on and off, and this strategy may allow the bacteria to display, at the same time, different external proteins and distract the immune system by directing its attacks to proteins which will be replaced again as needed.



This study provides some understanding of one of the mechanisms the persistent bacteria H. pylori uses to evade the immune system. The authors' efforts have been oriented to generate a vaccine against H. pylori, and although HopE and HopV are too infrequently expressed in clinical strains and so are not ideal candidate as antigens, they induce a good immune response (as tested in rabbits) and could be used in combination with other proteins in a multivalent vaccine. More research is needed to determine a strong immunogenic epitope or group of epitopes to direct the immune response towards H. pylori outer membrane proteins.



Reference:
Lienlaf M, Morales JP, D?­az MI, D?­az R, Bruce E, Siegel F, Le??n G, Harris PR, Venegas A. Helicobacter pylori HopE and HopV porins present scarce expression among clinical isolates. World J Gastroenterol 2010; 16(3): 320-329



Source:

Ye-Ru Wang


World Journal of Gastroenterology

Depressed Employees Vulnerable To Presenteeism And Absenteeism

A new study released today in the
American Journal of Psychiatry examines the impact depression has on work
productivity. The study, conducted by researchers at Tufts-New England
Medical Center, compared depressed employees with two groups: those with
rheumatoid arthritis (RA), which is a condition associated with work
disability, and depression-free healthy employees. When compared, the
depression group was far more vulnerable to job loss, absenteeism (missed
work days) and presenteeism (impaired productivity while at work).
Furthermore, the researchers noted that even when depressed subjects
received treatment and experienced improvement in their clinical symptoms,
their work productivity was still impaired.


"In order for the United States to remain competitive and innovative,
it's vital to address the physical and emotional burden of depression,"
said Lead Author and Co-Investigator David Adler, MD, Senior Psychiatrist
at Tufts-New England Medical Center. "Depression hits at all levels of
health, and figuring out new ways for people to improve functioning is more
important than ever."


The three groups were surveyed using reliable, validated
self-administrated questionnaires. The Work Limitations Questionnaire (WLQ)
developed under the direction of Debra Lerner, MS, PhD, Study Principal
Investigator and Director of Tufts-NEMC's Institute of Clinical Research's
Program on Health, Work and Productivity, was used to measure the effect of
chronic health problems on job performance and productivity. The Patient
Health Questionnaire-9 was utilized to both screen and follow patient's
depression. The National Institute of Mental Health funded the four-year
study.


The study enrolled 572 patients who were recruited from February 2001
and March 2003 from primary care physician offices covered by Tufts Health
Plan, the Fallon Clinic and Harvard Pilgrim Health Care. Participants were
followed for 18 months. At baseline, 44 percent of the depressed group was
taking antidepressants, but were still clinically depressed.


"Depression is an issue that effects employees, their families and
employers," said Dr. Lerner. The cost of lost productivity is staggeringly
large. "There is a prevailing myth that many chronically ill people prefer
to go out on disability, but our experience is that most want to continue
to work and feel productive. Also, many realize that disability benefits
will not fully replace earnings and will result in economic hardship.


Instituting increased and improved services to help people with depression
remain productive could be a win/win for both employers and employees."



E Tufts-New England Medical Center

nemc/home/

Risk Of Death For Heart Attack Patients Raised By Clinical Depression Even Years Later

Depressed heart attack patients have a higher risk for sudden death in the months following a heart attack. Now a team led by researchers from Washington University School of Medicine in St. Louis has found that the risk continues for many years.



"There's a two- to four-fold increase in a person's risk of dying following a heart attack if they also happen to be depressed," says Robert. M. Carney, Ph.D., lead author of the new study and professor of psychiatry at Washington University. "Previously we thought the impact of depression was strongest for the first three to six months following a heart attack and then gradually dropped off within a couple of years. Instead, we found that the effect lasts for at least five years."



Carney, with colleagues from Duke University Medical Center, Harvard University, Yale University, the National Heart, Lung and Blood Institute (NIH) and the Mayo Clinic, followed more than 750 heart attack patients for five years. The findings will appear in an upcoming issue of the Journal of Affective Disorders and are currently available online.



Patients followed in the study had participated in the NIH-funded project Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD). A little less than half were diagnosed with depression.



In the five years following a heart attack, 106 patients died. Of those, 62 had been diagnosed with depression, while 44 had not. In gauging the effects of depression, the investigators also considered other risks including age, smoking, hypertension, gender and diabetes.



Some of those factors, like younger age and female gender, lower mortality risk. Smoking and diabetes tend to raise the risk of dying. Carney says his team used statistical methods to evaluate the ways in which the various factors influenced mortality risk. Then they removed the influence of all other factors from the risk equation in order to consider the statistical impact of depression itself.



"We found that after adjusting for those risk factors, depression continues to play a statistically significant role," he says.



One possible explanation for depression's lingering influence on mortality is its recurring nature. Because the disorder can come and go over many years, it also may continue to increase the risk of death for many years.



"People typically are depressed for a while, then they'll either get better with treatment or it may subside on its own," Carney says. "But depression can always recur, and we think that because it is a recurring problem, whatever depression is doing to mortality risk after a heart attack, it continues doing for quite a long time."
















Past studies have differed over how much depression affects survival following a heart attack. But Carney believes these new findings are more reliable because all of the patients in this study were personally interviewed to determine their depression status, whereas other studies have relied on self-reporting.



"In our experience, self-reporting tends to overestimate the risk because it's often not possible to evaluate the causes of various symptoms on self-report questionnaires," he explains. "Say somebody reports having sleeping problems - that would go into the depression column as a symptom. But it's possible they are sleeping poorly because of a bad back or because they have to get up and go to the bathroom frequently during the night. During an interview, we can determine whether an individual symptom is related to depression or can be explained in some other way."



Carney's team also found that any clinically relevant depression increases the risk of death in heart attack patients. The risk was elevated both for patients with major depression, which requires the presence of five or more symptoms, and minor depression, which requires between two and four symptoms for diagnosis. Major depression was associated with higher risk, but minor depression also was associated with a significant increase in mortality risk.



Even with mounting evidence of a link between depression and death in heart attack patients, only about 25 to 30 percent of these patients receive antidepressant drugs or other depression treatments.



That doesn't surprise Carney. His team reported in 2003 in the Journal of the American Medical Association that providing treatment for depression seemed to have little effect on whether patients survived or had a second heart attack. This could be because the treatments don't work for all patients, Carney says, and he suggests if current depression treatments could be improved, survival rates might increase, too.



To this end, his team is studying whether omega-3 fatty acids - the fatty acids found in fish oil - might improve antidepressant therapies in heart patients. They're giving an antidepressant drug and a special formulation of omega-3 to some heart patients and comparing them to depressed heart patients who receive an antidepressant but no omega-3.



"We have not been satisfied with the effectiveness of standard antidepressants at alleviating depression in this population of patients," Carney says. "We're studying omega-3, because there's preliminary evidence that the fatty acids also might make depression therapies more effective, both in treating depression and in improving heart health."







Carney RM, Freedland KE, Steinmeyer B, Blumenthal JA, Berkman LF, Watkins LL, Czajkowski SM, Burg MM, Jaffe AS. Depression and five-year survival following acute myocardial infarction: a prospective study. Journal of Affective Disorders, 2008. doi:10.1016/j.jad.2007.12.005



Writing Committee for the ENRICHD Investigators. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the enhancing recovery in coronary heart disease patients (ENRICHD) randomized trial. Journal of the American Medical Association, vol. 289:23, pp. 3106-3116, June 18, 2003, with accompanying editorial on pp. 3171-3173.



This study was supported by grants from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, and from the Lewis and Jean Sachs Charitable Lead Trust, St. Louis, MO



The ENRICHD study was supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. Pfizer Inc. provided setraline (Zoloft) for that study.



Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's Hospitals. The School of Medicine is one of the leading medical research, teaching, and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's Hospitals, the School of Medicine is linked to BJC HealthCare.

Brain Pacemakers; A Long-lasting Solution In The Fight Against Depression

Nearly ten percent of all cases of depression are so severe that the patients do not respond to any established treatment method. Targeted stimulation of areas in the brain using a type of "brain pacemaker" has recently raised hopes: According to initial studies, half of patients with the most severe depression treated in this manner see a significant improvement in mood. Physicians from the University of Bonn, together with colleagues from the US, have suggested a new target structure for deep brain stimulation (as it is technically called). They hope to achieve an even better success rate with fewer side effects. The work has been published in the renowned "Neuroscience and Biobehavioral Reviews" (doi: 10.1016/j.neubiorev.2010.12.009).


In deep brain stimulation, physicians implant electrodes in the brain. Using an electrical pacemaker implanted under the patient's clavicle, physicians can influence the function of certain areas of the brain in a lasting manner. The method was originally developed for treating patients with Parkinson's disease, in order to alleviate the typical movement problems.


Lasting Improvement


For several years, the method has also been investigated in the treatment of the most severe cases of depression, with striking and completely unexpected success: In patients who had undergone many years of unsuccessful treatment, the symptoms sometimes significantly resolved. The most striking aspect: "Depression does not return in patients who responded to the stimulation," emphasizes Professor Dr. Thomas Schl?¤pfer from the Bonn Hospital for Psychiatry and Psychotherapy. "The method appears to have lasting effects - and this is in the case of the most treatment-resistant patient group described in the literature. This has never before happened."


Deep brain stimulation has been tested to date in three different areas of the brain: the nucleus accumbens, the internal capsule, and a structure known as cg25. Surprisingly, the effects are nearly identical - regardless of which of these centers the physicians stimulate. Together with colleagues from Baltimore and Washington, the Bonn researchers have since been able to explain why this is the case: Using a novel tomography method, they were able to make the "cable system" of the three brain centers visible. "In doing this, we determined that at least two of these three areas - probably even all three - are attached to one and the same cable harness," explains the Bonn brain surgeon, Professor Dr. Volker Coenen.


This is the so-called medial forebrain bundle, a structure which has been known in animals for a long time. The forebrain bundle forms a kind of feedback loop which allows us to anticipate positive experiences. "This circuit motivates us to take action," says Coenen. "In patients with depression, it is apparently disrupted. This results in, among other things, an extreme lack of drive - a characteristic symptom of the disease."


The nucleus accumbens, internal capsule, und cg25 all appear to be connected to the medial forebrain bundle - rather like leaves are connected to the branch from which they arise. Whoever stimulates one of these regions of the brain simultaneously influences the other components of the motivation circuit to a certain extent. Coenen, who was the first to anatomically describe the forebrain bundle in humans, now proposes implanting the electrode for deep brain stimulation directly into this structure. "We would use the electrode to send the current pulses to the base of the network and not to the periphery, as before," explains Schl?¤pfer. "We could thus potentially work with lower currents and yet achieve greater success."


A comparatively low-risk procedure


Observations of patients with Parkinson's disease appear to support this idea: in this case, a network of brain structures responsible for movements is stimulated. The more basally (figuratively speaking: near the branch) the electrical stimulation is applied, the greater its effect. At the same time, the risk of adverse side effects is reduced.


By now, more than 80,000 patients with Parkinson's disease worldwide have a brain pacemaker in their body. "Experiences to date demonstrate that the brain intervention necessary for this is relatively low-risk," stresses Professor Coenen. "Thus from a medical point of view, there is nothing that argues against also using this method to help people with very severe depression."


Sources: Bonn, Universitaet, AlphaGalileo Foundation.

Protein Handlers Should Be Effective Treatment Target For Cancer And Alzheimer's

Cancer and Alzheimer's have excess protein in common and scientists say learning more about how proteins are made and eliminated will lead to better treatment for both.



Medical College of Georgia researchers Drs. Nahid F. Mivechi and Dimitrios Moskofidis have received two National Cancer Institute grants totaling nearly $3 million and a $982,800, four-year grant from the U.S. Department of Veterans Affairs in the last 12 months to support studies of proteins and the molecular chaperones that manage them from cradle to grave.



Understanding the exact role molecular chaperones play in cancer and Alzheimer's should lead to better ways to intervene in both, says Dr. Mivechi, director of the MCG Center for Molecular Chaperone Biology/Radiobiology and Cancer Virology.



Everyone needs molecular chaperones which prompt genes to make proteins, move proteins around the body, fold them up into the proper shape to function properly and even haul them off when they no longer work. Cancer needs them even more for the endless cell replication required for tumor growth, Dr. Mivechi says. Essentially the opposite happens in Alzheimer's in which excess protein is a major component of the destructive brain plaque that is the disease's hallmark. Dr. Mivechi believes molecular chaperones, which typically slow in activity with age, are failing at their job so that proteins aggregate in the brain, contributing to Alzheimer's and other neurodegenerative diseases in which brain cell communication is interrupted.



The MCG center has evidence that disabling molecular chaperones or the heat shock factors that control some of them, disables tumor formation in the liver and probably the breast. Researchers are also now examining brain tumors as well as pancreatic and prostate cancer.



They also want to know whether ramping up the activity of molecular chaperone can essentially make them act young again and halt development of Alzheimer's, Parkinson's and other neurodegenerative diseases.



"We have to find the balance," Dr. Mivechi says of the center's concurrent work to find drugs that adjust the activity of molecular chaperones and heat shock factors. She theorizes these drugs would be used for limited periods to avoid trading cancer for an increased risk of neurodegenerative disease or vice versa.



"A lot of drugs, such as chemotherapeutic agents, can kill cancer but they also kill normal tissue. That is a limiting factor. We are looking for better drugs," she says.



The MCG center is among the first to study molecular chaperones and heat shock factors in animals to better understand their role in these diseases. Drs. Mivechi and Moskofidis, a viral immunologist, have developed 20 mouse models missing different molecular chaperones or heat shock factors in the last decade to help explore the large family of molecular chaperones. For contrast, they also have a mouse that over expresses heat shock factor 1, or Hsf1, a major activator of molecular chaperones.



They are now focusing on developing mice that lack molecular chaperones or heat shock factors in targeted areas, such as liver or breast tissue, as well as mice in which these can be removed during cancer to determine what impact their loss has on active disease. They also are cross breeding the mice, to create one, for example, that also over expresses the molecule, Her2/Neu, which is over active in some of the most aggressive breast cancers. By comparing the resulting mouse to one that just over expresses Her2/Neu, they can examine the impact of Hsf1, Dr. Mivechi says.



"That is how these findings will translate to patients," Dr. Mivechi says. "We need to know, not only how deleting or augmenting molecular chaperones and heat shock factors affects disease development, but also how it impacts disease progression."



Their studies also will help researchers pinpoint which molecular chaperones and/or heat shock factors are associated with a specific type of cancer or neurodegenerative disease which will help in the design of targeted therapies.



With the VA-funded study, for example, when they remove a specific molecular chaperone they find Alzheimer's-like disease accelerates dramatically in their animal model. They want to expand these studies to look at traumatic brain injury as well as other neurodegenerative diseases.



Source:
Toni Baker


Medical College of Georgia

Fathers As Well As Mothers Have Higher Depression Risk During First Year Of Child Being Born

Approximately one-fifth of all fathers and over one third of all mothers experience an episode of depression within the first 12 years of their child being born, with the first year having the highest risk, says a British study of 86,957 families published in Archives of Pediatrics & Adolescent Medicine, a JAMA/Archives publication. The authors say appropriate detection methods are needed to identify depression among both parents, fathers as well as mothers, and that doctors and other health care professionals should be aware of the depression risk factors in early parenthood.


The authors, who were supported by UK Medical Research Council, as background information in the article, wrote:


Depression in parents is associated with adverse behavioral, developmental and cognitive outcomes in their children. While the maternal depression and child outcome literature is well established, there are fewer studies on paternal depression. There is evidence that paternal depression is not uncommon, with rates higher than those in the general adult male population; however, a wide range of prevalence rates for paternal depression have been reported.



Shreya Dav?©, Ph.D., M.Sc., B.Sc., Medical Research Council, London, England, and team looked at occurrence, trends and correlates of parental depression in 86,957 families seen in British primary care (general practice) facilities during the period 1993-2007. They identified parents of both sexes with depression using diagnostic codes and pharmacy records.
br>
Overall, during the child's age of 0 to 12 years, the investigators found:

19,286 mothers had 23,176 episodes of depression
8,012 fathers had 9,683 episodes of depression
A depression rate of 7.53 per 100 mothers per year
A depression rate of 2.69 per 100 fathers per year
Highest rates were detected during the first year of a child's life, when 13.93 per 100 mothers and 3.56 per 100 fathers experienced depression.

The authors wrote:


These high rates of depression in the postpartum period are not surprising owing to the potential stress associated with the birth of a baby, e.g., poor parental sleep, the demands made on parents and the change in their responsibilities, and the pressure this could place on the couple's relationship. The high rate of parental depression in the first year after delivery may also be partly due to a resumption of antidepressant use following a break during pregnancy and breastfeeding.


There was a clearly higher risk of depression among parents aged 15 to 24 years when the child was born, who had a history of depression, compared to parents whose child was born when they were 25 years or older.



The researchers wrote:


There is a well-established link between depression and social and economic deprivation both in the general population and among parents. This finding may reflect the stresses of poverty, unemployment, low employment grade and lower social support among people of lower socioeconomic status. Younger parents may be less prepared for parenthood with more unplanned pregnancies and may be less able to deal with the stresses of parenthood compared with older parents.


As a result of these findings, the researchers suggest there is a need for appropriate detection of depression among parents of both sexes. Doctors should know about the risk factors for parental depression, and assess people who have those characteristics.


Future research should also look into other possible factors linked to parental depression, including stressful life events, the couple's relationship quality, as well as the separate and cumulative effects of paternal and maternal depression on the child's health and development, the investigators wrote.


"Incidence of Maternal and Paternal Depression in Primary Care - A Cohort Study Using a Primary Care Database"

Shreya Dav?©, PhD, MSc, BSc; Irene Petersen, PhD, MSc; Lorraine Sherr, PhD, Dip Clin Psych; Irwin Nazareth, MBBS, PhD

Arch Pediatr Adolesc Med. Published online September 6, 2010. doi:10.1001/archpediatrics.2010.184

Higher Levels Of Depression Experienced By ENT/Sleep Apnea Patients

Patients who experience a range of ear, nose, and throat-related health problems exhibited a greater prevalence of depression than is observed in the general population, says new research presented at the 2008 American Academy of Otolaryngology - Head and Neck Surgery Foundation (AAO-HNSF) Annual Meeting & OTO EXPO in Chicago, IL.



In any given one-year period, approximately 9.5 percent of the population, or about 18.8 million American adults suffer from a depressive illness. The new study, which analyzed the health of 12,516 distinct otolaryngology patients, found that 30 percent of these patients either had been diagnosed with depressive illness or took antidepressants.



The study further broke down different otolaryngologic diagnoses to determine which conditions had the highest co-morbidity with depression. Researchers found that patients diagnosed with sleep apnea had the highest levels of depression and use of antidepressant medications (21 percent and 46 percent).



Findings from this study could help clinicians diagnose and treat co-morbid depressive and otolaryngolic symptoms in patients.







Title: Prevalence of Depression in Otolaryngology Patients

Presenters: Victoria A. Epstein MD; Andrew J. Fishman, MD; Rakesh K. Chandra, MD

Date: September 21, 2008


About the AAO-HNS



The American Academy of Otolaryngology - Head and Neck Surgery (entnet/), one of the oldest medical associations in the nation, represents more than 12,000 physicians and allied health professionals who specialize in the diagnosis and treatment of disorders of the ears, nose, throat, and related structures of the head and neck. The Academy serves its members by facilitating the advancement of the science and art of medicine related to otolaryngology and by representing the specialty in governmental and socioeconomic issues. The organization's vision: "Empowering otolaryngologist-head and neck surgeons to deliver the best patient care."

Smoking Increases Risk Of Major Depression For Women - Royal College Of Psychiatrists

Women who smoke are at greater risk of developing major depressive disorder, according to new research published in the October issue of the British Journal of Psychiatry.



Researchers from the University of Melbourne studied a group of women in Australia, who had been followed for a decade as part of the Geelong Osteoporosis Study.



The results of a psychiatric test revealed that women with depression were more likely to have been smokers than those without depression. Among 165 women with major depressive disorder and 806 controls, smoking was clearly associated with increased odds for major depressive disorder. Indeed, the odds more than doubled for heavy smokers (those who smoked more than 20 cigarettes a day) compared with non-smokers.



The researchers also examined longitudinal data to determine the risk of women developing a new major depressive disorder over time. A total of 671 women with no history of major depressive disorders were studied.



Of the 87 women who were smokers, 13 went on to develop major depressive disorder. However, among 584 non-smokers, just 38 developed major depressive disorder during a decade of follow-up.



The researchers concluded that smoking increased the risk of major depressive disorder by 93%.



Previous research has shown that smoking is a risk factor for depression. There is also increasing evidence that smoking may aggravate mental illness or contribute to its onset. However, most previous studies have involved short time frames, and this study is the first to investigate smoking using longitudinal data that extends over a ten-year period.



The researchers observed that depression is a leading cause of global disease burden, and called for greater efforts to encourage smokers to quit.



Reference:


Pasco JA, Williams LJ, Jacka FN, Ng F, Henry MJ, Nicholson GC, Kotowicz MA and Berk M (2008) Tobacco smoking as a risk factor for major depressive disorder: population based study, British Journal of Psychiatry, 193: 322-326

The Royal College of Psychiatrists is the professional and educational body for psychiatrists in the United Kingdom and the Republic of Ireland. We promote mental health by:


- Setting standards and promoting excellence in mental health care

- Improving understanding through research and education

- Leading, representing, training and supporting psychiatrists

- Working with patients, carers and their organisations


As well as running its membership examination (MRCPsych), and visiting and approving hospitals for training purposes, the College organises scientific and clinical conferences and lectures and continuing professional development activities. The College publishes books, reports and educational material for professionals and the general public. It also publishes the British Journal of Psychiatry, Psychiatric Bulletin, Advances in Psychiatric Treatment and International Psychiatry, all of which are now available on-line.


The Royal College of Psychiatrists has been in existence in some form since 1841. First as the "Association of Medical Officers of Asylums and Hospitals for the Insane" (later changed to the Medico Psychological Association) then, in 1926 receiving its Royal Charter to become the "Royal Medico Psychological Association, and finally, in 1971 receiving a Supplemental Charter to become the "Royal College of Psychiatrists" we know today.


Royal College of Psychiatrists

Leads To Muscle Degeneration Uncovered By Massive MicroRNA Scan

Researchers have discovered the first microRNAs -- tiny bits of code that regulate gene activity -- linked to each of 10 major degenerative muscular disorders, opening doors to new treatments and a better biological understanding of these debilitating, poorly understood, often untreatable diseases. The study, to be published online this week by the Proceedings of the National Academy of Sciences, was led by Iris Eisenberg, PhD, of the Program in Genomics at Children's Hospital Boston. Louis Kunkel, PhD, director of the Program in Genomics and an investigator with the Howard Hughes Medical Institute, was senior investigator.



The disorders include the muscular dystrophies (Duchenne muscular dystrophy, Becker muscular dystrophy, limb girdle muscular dystrophies, Miyoshi myopathy, and fascioscapulohumeral muscular dystrophy); the congenital myopathies (nemaline myopathy); and the inflammatory myopathies (polymyositis, dermatomyositis, and inclusion body myositis). While past studies have linked them with an increasing number of genes, it's still largely unknown how these genes cause muscle weakness and wasting, and, more importantly, how to translate the discoveries into treatments.



For instance, most muscular dystrophies begin with a known mutation in a "master gene," leading to damaged or absent proteins in muscle cells. In Duchenne and Becker muscular dystrophies, the absent protein is dystrophin, as Kunkel himself discovered in 1987. Its absence causes muscle tissue to weaken and rupture, and the tissue becomes progressively nonfunctional through inflammatory attacks and other damaging events that aren't fully understood.



"The initial mutations do not explain why patients are losing their muscle so fast," says Eisenberg. "There are still many unknown genes involved in these processes, as well as in the inflammatory processes taking place in the damaged muscle tissue."



She and Kunkel believe microRNAs may help provide the missing genetic links. Their team analyzed muscle tissue from patients with each of the ten muscular disorders, discovering that 185 microRNAs are either too abundant or too scarce in wasting muscle, compared with healthy muscle.



Discovered in humans only in the past decade, microRNAs are already known to regulate major processes in the body. Therefore, Eisenberg believes microRNAs may be involved in orchestrating the tissue death, inflammatory response and other major degenerative processes in the affected muscle tissue. The researchers used bioinformatics to uncover a list of genes the microRNAs may act on, and now plan to find which microRNAs and genes actually underlie these processes.



The findings raise the possibility of slowing muscle loss by targeting the microRNAs that control these "cascades" of damaging events. This approach is more efficient than targeting individual genes.
















The team also defined the abnormal microRNA "signatures" that correspond to each of the ten wasting diseases. They hope these will shed light on the genes and disease mechanisms involved in the most poorly understood and least treatable of the degenerative disorders, such as inclusion body myositis.



"At this point, it's very theoretical, but it's possible," says Eisenberg.







The study was funded by the Howard Hughes Medical Institute and also by the National Center for Research Resources, the Associazione Amici del Centro Dino Ferrari, the Telethon Project, the Eurobiobank Project, the Muscular Dystrophy Association, the National Institutes of Health, the Lee and Penny Anderson Family Foundation, and the Joshua Frase Foundation.



Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 11 members of the Institute of Medicine and 12 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 377-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital and its research visit: childrenshospital/newsroom.



Source: James Newton


Children's Hospital Boston

Severe depression associated with greater number of nerve cells in thalamus region of brain

Individuals who suffer from severe depression have more nerve cells in the part of the brain that controls emotion, researchers at UT Southwestern Medical Center at Dallas have found.


Individuals who suffer from severe depression have more nerve cells in the part of the brain that controls emotion, researchers at UT Southwestern Medical Center at Dallas have found.


Studies of postmortem brains of patients diagnosed with major depressive disorder (MDD) showed a 31 percent greater than average number of nerve cells in the portion of the thalamus involved with emotional regulation. Researchers also discovered that this portion of the thalamus is physically larger than normal in people with MDD. Located in the center of the brain, the thalamus is involved with many different brain functions, including relaying information from other parts of the brain to the cerebral cortex.


The findings, published in today's issue of The American Journal of Psychiatry, are the first to directly link a psychiatric disorder with an increase in total regional nerve cells, said Dr. Dwight German, professor of psychiatry at UT Southwestern.


"This supports the hypothesis that structural abnormalities in the brain are responsible for depression," he said. "Often people don't understand why mentally ill people behave in odd ways. They may think they have a weak will or were brought up in some unusual way.


"But if their brains are different, they're going to behave differently. Depression is an emotional disorder. So it makes sense that the part of the brain that is involved in emotional regulation is physically different."


Four groups were represented in the study: subjects with major depression, with bipolar disorder and with schizophrenia, as well as a comparison group with no history of mental illness. Major depression is characterized by a depressed mood and lack of interest or pleasure in normal activities for a prolonged period of time, while bipolar disease is distinguished by alternating periods of extreme mania or elevated mood swings, and severe depression. Schizophrenia often results in psychotic episodes of hallucinations and delusions and a lack of perception of reality.


Brain specimens were provided by the Stanley Foundation Brain Bank, which collects donated postmortem brains for research on mental illness, and the subjects were matched according to age, gender, brain weight and other variables.


Researchers from UT Southwestern, working with a team from Texas A&M University System Health Science Center, used special computer-imaging systems to meticulously count the number of nerve cells in the thalamus.


Results showed an increase of 37 percent and 26 percent, respectively, in the number of nerve cells in the mediodorsal and anteroventral/anteromedial areas of the thalamus in subjects with MDD when compared with similar cells in those with no psychiatric problems. The number of nerve cells in subjects with bipolar disorder and schizophrenia was normal.















Researchers also found that the size of the affected areas of the thalamus in subjects with MDD was 16 percent larger than those in the other groups.



"The thalamus is often referred to as the secretary of the cerebral cortex - the part of the brain that controls all kinds of important functions such as seeing, talking, moving, thinking and memory," Dr. German said. "Most everything that goes into the cortex has to go through the thalamus first.



"The thalamus also contains cells that are not involved with emotion. Our studies found these portions of the thalamus to be perfectly normal. But the ones that are involved in emotion are the ones that were abnormal."



Researchers also looked at the effect of antidepressant medications on the number of nerve cells and found no significant difference among any of the subject groups - whether they had taken antidepressants or not - reinforcing the belief that abnormalities in brain development are responsible for depression.



Other researchers involved in the study were Dr. Umar Yazdani, a postdoctoral researcher in psychiatry from UT Southwestern, and Drs. Keith A. Young, Leigh A. Holcomb and Paul B. Hicks from Central Texas Veterans Health Care System, Texas A&M University System Health Science Center and Scott & White Hospital in Temple.



The research was supported by the National Institutes of Health; the Veterans Administration; the Scott, Sherwood and Brindley Foundation, and the Theodore and Vada Stanley Foundation.



This news release is available on our World Wide Web home page at
utsouthwestern/home/news/index.html


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Contact: Donna Steph Hansard

donna.hansardutsouthwestern

214-648-3404

University of Texas Southwestern Medical Center at Dallas

Embracing Your Primitive Nature Can Help In Fight Against Depression

He doesn't care for the term "caveman therapy." But Stephen Ilardi, associate professor of clinical psychology at the University of Kansas, has turned to our hunter-gatherer ancestors for clues about how to best combat major depressive disorder.



Further, Ilardi fingers our modern, industrialized lifestyle as the key culprit behind the burgeoning depression epidemic, which continues to worsen despite decades of sharp increases in pharmaceutical consumption.



"A century ago, according to the best epidemiological evidence we have, the lifetime rate of depressive illness in the U.S. was about 1 percent," said Ilardi. "The rate now stands at 23 percent. So we've had roughly a 20-fold increase over the course of a century. Since World War II there's been roughly a 10-fold increase. And a recent study found the rate of depression has more than doubled in just the past decade."



Published June 1, Ilardi's book, "The Depression Cure" (Da Capo Lifelong Books), is based on research suggesting that depression can be treated effectively by helping people reclaim healing habits from a more primitive way of life. In fact, Ilardi thinks this may be a superior approach than modern psychotherapy or antidepressant drugs, which typically work for only about half the patients who try them.



The KU researcher heads a large treatment study, dubbed the Therapeutic Lifestyle Change project, which calls for patients to adopt six healing elements from the ancient past: consuming more omega-3 fatty acids; using engaging activity to combat rumination; getting regular sunlight exposure; increasing physical exercise; connecting more with others socially; and getting increased (and healthier) sleep.



"As a species, humans were never designed for the pace of modern life," said Ilardi. "We're designed for a different time - a time when people were physically active, when they were outside in the sun for most of the day, when they had extensive social connections and enjoyed continual face time with their friends and loved ones, when they experienced very little social isolation, when they had a much different diet, when they got considerably more sleep and when they had much less in the way of a relentless, demanding, stress-filled existence."



Many elements of the hunter-gatherer lifestyle are robustly antidepressant, Ilardi said. In fact, the KU psychology professor mused that if the neurological benefits of exercise alone could be concentrated into a pill, it would become the best-selling, most-effective antidepressant ever marketed.



In addition to positive results from his own ongoing research study, Ilardi points to low rates of depression among contemporary peoples whose lifestyles mirror those of our ancestors. The American Amish, for example, have rates of depressive illness far lower than that of the broader American population. Likewise, anthropologist Edward Schieffelin observed that the Kaluli people of the New Guinea highlands - whose day-to-day existence of foraging and gardening is akin to that of our remote ancestors - are almost completely free of depressive illness.



For Ilardi, such findings are conclusive that depression primarily stems from modern living: social isolation, fast-food-laden diets, physical inactivity, sleep deprivation and less exposure to the outdoors.



Indeed, one in four Americans will experience depression during their lifetime. Ilardi asserted that depression is that largest single cause of work-related disability, one that increases a person's lifelong risk of heart disease, of some types of cancer and many forms of inflammatory illness. The psychology expert said depression can even become neurotoxic, leading to brain damage by suppressing levels of a key neural growth hormone needed to repair and maintain brain tissue.



The KU researcher said his passion for curing depression is personal.



"I've seen three of my own family members battle this illness, and I don't think anyone can encounter depression up close without gaining a greater sense of compassion for those who are suffering in its grip," he said. "It's something that hits very close to home for me and probably for many others. Virtually everyone knows someone with this affliction."

Targeted Programs Reduced Depression In Youth Better Than Nontargted Programs

Depression among youth is a growing public health concern, affecting one to two percent of elementary school-aged children and three to eight percent of adolescents. To determine what programs are effective in preventing depressive symptoms, researchers from Vanderbilt University conducted a meta-analysis of the last 20 years of research on interventions aimed at preventing depressive symptoms in youth. The results of the study appearing in the June issue of the Journal of Consulting and Clinical Psychology, published by the American Psychological Association (APA), showed that targeted interventions for those at risk for depression have greater effect sizes than universal interventions.



Thirty studies were reviewed on how well different intervention programs worked in preventing depressive symptoms among children and adolescents. Three different types of interventions were examined: universal, selective, and indicated programs, said researchers Jason L. Horowitz, MS, and Judy Garber, PhD, of Vanderbilt University. Universal preventive interventions are provided to all members of a particular population. Selective prevention programs are used for members of a subgroup of a population whose risk is considered above average. Finally, indicated preventive interventions are for individuals who show early signs or symptoms of a psychological disorder.



According to the findings of the meta-analysis, both selective and indicated prevention programs had greater effect sizes than universal programs in alleviating depressive symptoms at post-intervention and at a six-month follow up. This may have been due to the fact that very large samples are needed to show an effect in studies using universal samples. That is, it is not necessarily that universal programs are not effective, but that studies may not have had the power to detect significant effects. Moreover, universal programs, which often are conducted in schools in large group formats, do a good job at avoiding the stigma of singling out individuals for intervention, do not require prescreening, and have a relatively low dropout rate.



In contrast, Horowitz and Garber showed that selective programs, which target individuals who are more at risk for depression because of exposure to such factors as parental divorce, deaths, parental depression or alcoholism, or poverty, produced a significantly larger effect size in reducing depressive symptoms compared to universal programs. Selective programs usually involve a more diverse sample, are more varied in their delivery of information, and target other outcomes besides depression (e.g. academic improvement, parent-child relationship).



Indicated programs, which are used for individuals who are already showing signs and symptoms of depression and are at increased risk of experiencing clinical depression, also showed a significantly greater effect size than universal programs, said Horowitz and Garber. Like selective programs, indicated programs typically use small group format, teach cognitive techniques that emphasize reducing negative thinking, increase problem-solving skills and goal setting, and show participants how to look at events from another perspective.
















Age and gender also moderated the effect of the interventions on reducing depressive symptoms. Older female adolescents who participated in an intervention were more likely to have lower levels of symptoms at post-intervention.



The authors also highlighted the distinction between treatment and prevention effects, and showed that the studies reviewed in the meta-analysis appeared to be more effective in reducing symptoms of depression (i.e., treatment) rather than in preventing the worsening of depressive symptoms. Only 4 of the 30 studies showed evidence of an actual prevention effect.



To design better prevention programs for children and adolescents, said Horowitz and Garber, future studies should focus on targeted populations that include female adolescents, offspring of depressed parents, youth with elevated depression and/or anxiety symptoms themselves, and youth who have been exposed to stressors, such as parental psychopathology, divorce, or death. Studies also should have longer follow up evaluations to measure whether a preventive effect occurred.







Article: "The Prevention of Depressive Symptoms in Children and Adolescents: A Meta-Analytic Review," Jason L. Horowitz, MS, and Judy Garber, PhD, Vanderbilt University; Journal of Consulting and Clinical Psychology, Vol. 74, No.3.



Full text of the article is available from the APA Public Affairs Office or at apa/releases/ccp743-horowitz.pdf Jason L. Horowitz, PhD, Vanderbilt University; email:mailto:jason.horowitzvanderbilt



Judy Garber, PhD, Vanderbilt University; email: mailto:judy.garbervanderbilt



The American Psychological Association (APA), in Washington, DC, is the largest scientific and professional organization representing psychology in the United States and is the world's largest association of psychologists. APA's membership includes more than 150,000 researchers, educators, clinicians, consultants and students. Through its divisions in 54 subfields of psychology and affiliations with 60 state, territorial and Canadian provincial associations, APA works to advance psychology as a science, as a profession and as a means of promoting health, education and human welfare.



Contact: Pam Willenz



American Psychological Association

Discovery of the genetic basis of two diseases

In a first article, Loeys et al describe a new aortic aneurysm syndrome characterized by the main triad of hypertelorism,
bifid uvula and/or cleft palate and aortic aneurysms with arterial tortuosity. This new entity also presents with alterations
of the skeletal, craniofacial, neurocognitve development. Importantly, the nature of the aortic aneurysms seems very
aggressive and aneurysms occur throughout the arterial tree. In a collaboration between Johns Hopkins University in Baltimore
and Ghent University in Belgium, it was demonstrated that this disease is caused by mutations in either of the genes encoding
for transforming growth factor receptor 1 or 2 (TGFBR1 or 2).


In a second article, homozygosity mapping of a Senior-Loken family evaluated at the Ghent University led to the idenfication
of a region on the long arm of chromosome 3. Researchers of the Ann Harbor University in Michigan went on to clone a new
gene, nephrocystin-5, a ciliary IQ domain protein. Senior-Loken syndrome is characterized by the association of
nephronophtisis and retinitis pigmentosa. These studies emphasize the central role of ciliary dysfunction in the pathogenesis
of Senior-Loken syndrome.


Peer reviewed publication and references

Nature Genetics, 2005, 37: 275-281.

Nature Genetics, 2005, 37: 282-288.


A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or
TGFBR2.

Loeys B., Chen J., Neptune E.R., Judge D.P., Podowski M., Holm T., Meyers J., Leitch C.C., Katsanis N., Sharifi N., Xu F.L.,
Myers L.A., De Backer J., Hellemans J., Chen Y., Davis E.C., Webb C.L., Kress W., Spevak P.J., Coucke P., Rifkin D.B., De
Paepe A., Dietz H.C.

Nature Genetics, 2005, 37: 275-281.


Nephrocystin-5, a ciliary IQ domain protein is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin.

Otto E.A., Loeys B., Kahnna H., Hellemans J., Sudbrak R., Fan S., Muerb U., O'Toole J.F., Helou J., Attanasio M., Utsch B.,
Sayer J.A., Lillo C., Jimeno D., Coucke P., De Paepe A., Reinhardt R., Klages S., Tsuda M., Kawakami I., Kusakabe T., Omran
H., Imm A., Tippens M., Raymond P.A., Hill J., Beales P., He S., Kispert A., Margolis B., Williams D.S., Swaroop A.,
Hildebrandt F.

Nature Genetics, 2005, 37: 282-288.


GHENT UNIVERSITY

(The largest and oldest public university in Belgium)

Het Pand,

Onderbergen 1,

B-9000 Gent,

rug.ac.be

SOURCE: alphagalileo

Few Americans With Major Depression Receive Adequate Treatment

Many U.S. adults with major depression do not receive treatment for depression or therapy based on treatment guidelines, and some racial and ethnic groups have even lower rates of adequate depression care, according to a report in the January issue of Archives of General Psychiatry, one of the JAMA/Archives journals.


Depression is a leading cause of disability among many racial and ethnic groups in the United States, according to background information in the article. Pharmacotherapy (including antidepressants) and psychotherapy are both effective, well tolerated treatments for depression when provided according to established guidelines (such as those from the American Psychiatric Association), the authors note. Previous research suggests that many individuals are untreated or undertreated, but most studies of depression care have not distinguished between the two modalities and have also aggregated major racial and ethnic groups (for instance, combining all Latino individuals instead of examining specific subgroups, such as Mexican Americans and Puerto Ricans).


Hector M. Gonz??lez, Ph.D., of Wayne State University, Detroit, and colleagues assessed the prevalence and adequacy of depression care among different racial and ethnic groups in the United States by analyzing data from the National Institute of Mental Health's Collaborative Psychiatric Epidemiology Surveys. This initiative combines three nationally representative studies, during which face-to-face interviews were conducted with 15,762 individuals age 18 and older throughout the country between 2001 and 2003.


Of the adults surveyed, 8.3 percent had major depression, including 8 percent of Mexican Americans, 11.8 percent of Puerto Ricans, 7.9 percent of Caribbean blacks, 6.7 percent of African Americans and 8.5 percent of non-Latino whites.


Overall, more than half of those with depression received at least one form of depression care, but only about one in five (21.3 percent) had received at least one form of therapy that conformed to established treatment guidelines within the previous year. Psychotherapy was more commonly used than pharmacotherapy, and individuals undergoing psychotherapy were more likely to receive treatment in alignment with clinical guidelines than were individuals taking medications.


Mexican American and African American individuals with depression consistently had lower odds of receiving any type of care or care in concordance with treatment guidelines during the year prior. "The proportions of Puerto Rican and non-Latino white individuals who used concordant therapies in the past year were nearly twice those of Mexican American, Caribbean black and African American individuals," the authors write.


The findings illustrate the importance of breaking down large ethnic and racial groups into smaller sub-categories, they note. "Failing to do so obscures depression care research, especially for the largest and fastest-growing segment of the U.S. population, Latino individuals, and especially Mexican American individuals."


"With the recent passing of a U.S. Mental Health Parity Act, our findings should provide guidance to better-enabled mental health to improve the depression care of all Americans and for reducing disparities among ethnic/racial minorities," they conclude.


Source
American Medical Association (AMA)

Migrating birds offer insight into sleep

A newly published study by a University of Wisconsin research team points the way to solving two of life's seemingly eternal but unrelated mysteries: how birds that migrate thousands of miles every year accomplish the feat on very little sleep and what that ability means for humans who are seriously sleep-deprived or face significant sleep problems.


The study, published online in the July 13 issue of PloS (Public Library of Science) Biology, found that a group of sparrows studied in the laboratory dramatically reduced how long they slept during the time they would ordinarily be migrating. But they were nonetheless able to function and perform normally despite their sleep deprivation. During times when the birds were not migrating, however, sleep deprivation appeared to impair their performance - similar to what happens to sleep-deprived humans.


If researchers ascertain how the birds do so well on so little sleep during migration, the finding could benefit people who need to stay awake and function at a high level for long periods of time, as well as those who suffer from sleep disorders of various kinds. In addition, sleep in the migrating birds was similar to sleep changes that typically occur in humans with depression or bipolar disorder.


"We already know from human studies that people with severe depression and mania show characteristic changes in their sleep patterns, such as having insomnia and entering REM sleep (the dream stage) too quickly after falling asleep," says Ruth Benca, professor of psychiatry at UW Medical School and principal investigator of the study. "Finding this same pattern in the birds offers us an intriguing model for studying mechanisms for seasonal mood disorders, such as bipolar illness."



Benca and her colleagues studied captive white-crowned sparrows, songbirds that normally migrate at night between Alaska and Southern California twice a year. When in captivity in laboratory cages during periods when they would normally be migrating, the birds become active and restless at night, moving around and flapping their wings.



Brain sensors measure their sleep patterns continuously during migratory and non-migratory periods. During "migrating" times, they slept about one-third as much as usual and moved more quickly into REM sleep, marked by rapid eye movements. At night, when the birds were active, the brain recordings showed they were fully awake, and they did not appear to make up their lost nocturnal sleep with increased napping during the day.



Cognitive tests showed that, during the migration periods, the birds performed normally -- or even improved their ability to learn -- on little sleep; but during other times, sleep deprivation hurt their performance. The researchers theorize that migrating songbirds have developed the ability to apparently reduce their need for sleep temporarily, without suffering the consequences of sleep deprivation. While the researchers do not know how the birds do what they do, they are convinced that the birds' behavior sheds light on sleep processes in general and on some human disorders as well.



The Wisconsin researchers are also affiliated with the UW HealthEmotions Research Institute, created to study the scientific basis of emotion and health.


Contact: Lisa Brunette

la.brunettehosp.wisc

608-263-5830

University of Wisconsin-Madison