In spite that the causes of depression have not still been fully identified, scientists acknowledge that genetic and environmental factors play a common role in the onset of this disorder. One of the environmental risk factors more often related to depression is exposure to threatening life events. On the other side, from a genetic point of view, the serotonin transporter gene, with a crucial role in communication between neurons, could predispose to depression.
An international group of scientists, headed by professors Jorge Cervilla Ballesteros and Blanca Gutiérrez Martínez, from the department of Legal Medicine, Toxicology and Psychiatry of the University of Granada, has recently published in the prestigious journal Molecular Psychiatry the pioneering study PREDICT-gene, confirming the relation between allele s in the serotonin transporter gene and exposure to threatening life events in the onset of depression. The study proves, for a population sample accounting for gender, age and family history of psychiatric disorders, that 24% of the Spanish population, comprising people with the s/s genotype, need minimal exposure to threatening life events, unlike individuals with s/l or l/l genotypes, thus confirming the relation between genetic and environmental factors in this mental disorder.
The most important consequence of research on interaction between genetic and environmental factors is that, in a foreseeable future, scientists will be able to produce measures to predict response to antidepressants taking into account each individual’s genotype, i. e. they will be able to design tailor-made drugs according to each person’s genetic configuration and their exposure to environmental factors.
The research group headed by professor Cervilla Ballesteros and Gutiérrez Martínez is currently working at the University of Granada to open roads for psycho-pharmaco-genetics, a field that will allow for individual treatments, tailor-made drugs, for each patient with depression, a disorder affecting one in every five Spaniards visiting the doctor’s.
This study is framed in the international project PREDICT and is funded by the European Union and the Spanish Ministry of Education and Science. One of its most important novelties is that it has been carried out through a very representative sample: a total of 737 people agreed to participate in the genetic tests, with ages ranging from 18 to 75, patients of nine primary care centres in the South of Spain. That is why this is the first representative population-based replication of earlier research, as until now research had been done into restricted population samples, comprising only women, adolescents, twins or people with affective disorders.
Contact: Professor Jorge Cervilla Ballesteros
Universidad de Granada
The most accurate measures of European daily temperatures ever indicate that the length of heat waves on the continent has doubled and the frequency of extremely hot days has nearly tripled in the past century. The new data shows that many previous assessments of daily summer temperature change underestimated heat wave events in western Europe by approximately 30 percent.
Paul Della-Marta and a team of researchers at the University of Bern in Switzerland compiled evidence from 54 high-quality recording locations from Sweden to Croatia and report that heat waves last an average of 3 days now—with some lasting up to 4.5 days—compared to an average of around 1.5 days in 1880. The results are published 3 August in the Journal of Geophysical Research-Atmospheres, a publication of the American Geophysical Union. The researchers suggest that their conclusions contribute to growing evidence that western Europe’s climate has become more extreme and confirm a previously hypothesized increase in the variance of daily summer temperatures since the 19th century.
The study adds evidence that heat waves, such as the devastating 2003 event in western Europe, are a likely sign of global warming; one that perhaps began as early as the 1950s, when their study showed some of the highest trends in summer mean temperature and summer temperature variance.
“These results add more evidence to the belief among climate scientists that western Europe will experience some of the highest environmental and social impacts of climate change and continue to experience devastating hot summers like the summer of 2003 more frequently in the future,” Della-Marta said.
The authors note that temperature records were likely overestimated in the past, when thermometers were not kept in modern Stevenson screens, which are instrument shelters used to protect temperature sensors from outside influences that could alter its readings. The researchers corrected for this warm bias and other biases in the variability of daily summer temperatures and show that nearly 40 percent of the changes in the frequency of hot days are likely to be caused by increases in summer temperatures’ variability. This finding demonstrates that even a small change in the variance of daily summer temperatures can radically enhance the number of extremely hot days.
“These findings provide observational support to climate modeling studies showing that European summer temperatures are particularly sensitive to global warming,” Della-Marta said. “Due to complex reactions between the summer atmosphere and the land, the variability of summer temperatures is expected to [continue to] increase substantially by 2100.”
The research was supported by the European Environment and Sustainable Development Program, the Swiss National Science Foundation and the National Center for Excellence in Climate Research (NCCR Climate).
Contact: Jonathan Lifland
American Geophysical Union
Review covers 136 countries in US, Canada, UK, France, Germany, Japan and Spain
Leukaemia rates in children and young people are elevated near nuclear facilities, but no clear explanation exists to explain the rise, according to a research review published in the July issue of European Journal of Cancer Care.
Researchers at the Medical University of South Carolina carried out a sophisticated meta-analysis of 17 research papers covering 136 nuclear sites in the UK, Canada, France, the USA, Germany, Japan and Spain.
They found that death rates for children up to the age of nine were elevated by between five and 24 per cent, depending on their proximity to nuclear facilities, and by two to 18 per cent in children and young people up to the age of 25.
Incidence rates were increased by 14 to 21 per cent in zero to nine year olds and seven to ten percent in zero to 25 year-olds.
“Childhood leukaemia is a rare disease and nuclear sites are commonly found in rural areas, which means that sample sizes tend to be small” says lead author Dr Peter J Baker.
“The advantage of carrying out a meta-analysis is that it enables us to draw together a number of studies that have employed common methods and draw wider conclusions.”
Eight separate analyses were performed – including unadjusted, random and fixed effect models – and the figures they produced showed considerable consistency.
But the authors point out that dose-response studies they looked at – which describe how an organism is affected by different levels of exposure – did not show excess rates near nuclear facilities.
“Several difficulties arise when conducting dose-response studies in an epidemiological setting as they rely on a wide range of factors that are often hard to quantify” explains Dr Baker. “It is also possible that there are environmental issues involved that we don’t yet understand.
“If the amount of exposure were too low to cause the excess risk, we would expect leukaemia rates to remain consistent before and after the start-up of a nuclear facility. However, our meta-analysis, consistently showed elevated illness and death rates for children and young people living near nuclear facilities.”
The research review looked at studies carried out between 1984 and 1999, focusing on research that provided statistics for individual sites on children and young people aged from zero to 25.
Four studies covered the UK, with a further three covering just Scotland. Three covered France, two looked at Canada and there was one study each from the USA, Japan, Spain, the former East Germany and the former West Germany.
“Although our meta-analysis found consistently elevated rates of leukaemia near nuclear facilities, it is important to note that there are still many questions to be answered, not least about why these rates increase” concludes Dr Baker.
“Several hypotheses have been proposed to explain the excess of childhood leukaemia in the vicinity of nuclear facilities, including environmental exposure and parental exposure. Professor Kinlen from Oxford University has also put forward a hypothesis that viral transmission, caused by mixing populations in a new rural location, could be responsible.
“It is clear that further research is needed into this important subject.”
Notes to editors
Meta-analysis of standardized incidence and mortality rates of childhood leukaemia in proximity to nuclear facilities. Baker PJ and Hoel D. European Journal of Cancer Care. 16, pages 355-363. July 2007.
The European Journal of Cancer Care provides a medium for communicating multi-professional cancer care across Europe and internationally. The Journal publishes peer-reviewed papers, reviews, reports, features and news, and provides a means of recording lively debate and an exchange of ideas. It is published six times a year by Blackwell Publishing.
Blackwell Publishing is the world’s leading society publisher, partnering with 665 medical, academic, and professional societies. Blackwell publishes over 800 journals and has over 6,000 books in print. The company employs over 1,000 staff members in offices in the US, UK, Australia, China, Singapore, Denmark, Germany and Japan and officially merged with John Wiley & Sons, Inc’s Scientific, Technical and Medical business in February 2007. Blackwell’s mission as an expert publisher is to create long-term partnerships with our clients that enhance learning, disseminate research, and improve the quality of professional practice. For more information on Blackwell Publishing, please visit http://www.blackwellpublishing.com or http://www.blackwell-synergy.com
Contact: Annette Whibley
Blackwell Publishing Ltd.
Disturbed sleep associated with decline in cognition over time; no link with total hours of sleep per night
Women who experienced cognitive decline over a 13 to 15 year period after age 65 were more likely to sleep poorly than women whose cognition did not decline, according to a study led by researchers at the San Francisco VA Medical Center (SFVAMC).
The women’s cognitive decline was associated with interrupted or fitful sleep. Total sleep time per night made no difference, says lead author Kristine Yaffe, MD, chief of geriatric psychiatry at SFVAMC and professor of psychiatry, neurology, epidemiology, and biostatistics at the University of California, San Francisco (UCSF).
“This indicates that it’s not how long you sleep, but how well you sleep,” she says.
The study appears in the July 17, 2007 issue of Neurology.
Yaffe speculates that there are three possible explanations for the association between cognitive decline and disturbed sleep. She says the first and most likely reason is that whatever neurodegenerative condition is starting to cause cognitive decline, such as Alzheimer’s disease, is also affecting areas of the brain that govern sleep.
“Sleep is very complex,” notes Yaffe. “It involves a coordinated series of neurologic functions that we don’t entirely understand. It’s not unlikely that early neurodegenerative disease could start having an effect on sleep centers as well.”
Another possibility is that someone who is becoming cognitively impaired is sleeping poorly “because they’re aware of their condition and they’re worried about it.”
Finally, Yaffe says that other factors entirely, such as brain inflammation or genetic changes, might cause both cognitive decline and sleep disturbance at the same time.
The researchers studied 2,474 women who were part of a larger ongoing prospective study of risk factors for osteoporosis that began in 1986. The mean age of the women was 68.9 years at the beginning of the study. Their cognitive health was measured at regular intervals over the course of the study using two standard cognitive tests: the Mini-Mental State Examination and the Trail Making Test, Part B, known as Trails B.
After 13 to 15 years in the study, the women were fitted with an actigraph, a small device worn on the wrist that measures movement and is known from previous studies to be highly accurate in differentiating sleep from wakefulness. The women wore the device for at least three consecutive 24-hour periods.
Women who performed progressively worse on both cognitive tests over time were significantly more likely to have difficulty falling asleep and staying asleep than women whose performance did not decline. Women who performed progressively worse on the Trails B test also napped significantly more during the day.
The association between cognitive decline and poor sleep remained even after the researchers adjusted for a host of other demographic factors such as age, education, depression, exercise, and health status.
“It’s been known for some time that people with cognitive problems often have sleep problems, but those studies have mostly been done on severely demented people in nursing homes,” observes Yaffe. “Ours was the first study to look at the relationship between sleep and cognition in healthy women dwelling in the community who did not have dementia to begin with.”
Yaffe offers several cautions concerning the results of the study. First, men and African-American women were excluded from the original osteoporosis study because both of those groups have low incidence of osteoporotic fractures. Additionally, sleep patterns were measured only once, “so it’s more of a snapshot.”
However, Yaffe says that the research group has received a grant from the National Institutes of Health to continue tracking sleep patterns and cognitive health over time in the same study cohort. “Hopefully, we’ll be able to tell if cognitive changes lead to sleep disturbances, or if the reverse is true, or if they have a common independent cause.”
Co-authors of the paper were Terri Blackwell, MA, of the California Pacific Medical Center Research Institute (CPMCRI); Deborah E. Barnes, PhD, of SFVAMC and UCSF; Sonia Ancoli-Israel, PhD, of the University of California, San Diego and the VA San Diego Healthcare System; and Katie Stone, PhD, of CPMCRI, for the Study of Osteopororic Fractures Group.
The study was supported by grants from the National Institutes of Health and the National Institute on Aging.
SFVAMC has the largest medical research program in the national VA system, with more than 200 research scientists, all of whom are faculty members at UCSF.
UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.
Contact: Steve Tokar
University of California – San Francisco
Scientists have only recently begun to speculate that what’s referred to as “junk” DNA – the 96 percent of the human genome that doesn’t encode for proteins and previously seemed to have no useful purpose – is present in the genome for an important reason. But it wasn’t clear what the reason was. Now, researchers at the University of California, San Diego (UCSD) School of Medicine have discovered one important function of so-called junk DNA.
Genes, which make up about four percent of the genome, encode for proteins, “the building blocks of life.” An international collaboration of scientists led by Michael G. Rosenfeld, M.D., Howard Hughes Medical Investigator and UCSD professor of medicine, found that some of the remaining 96 percent of genomic material might be important in the formation of boundaries that help properly organize these building blocks. Their work will be published in the July 13 issue of the journal Science.
“Some of the ‘junk’ DNA might be considered ‘punctuation marks’ – commas and periods that help make sense of the coding portion of the genome,” said first author Victoria Lunyak, Ph.D., assistant research scientist at UCSD.
In mice, as in humans, only about 4 percent of the genome encodes for protein function; the remainder, or “junk” DNA, represents repetitive and non-coding sequences. The research team studied a repeated genomic sequence called SINE B2, which is located on the growth hormone gene locus, the gene related to the aging process and longevity. The scientists were surprised to find that SINE B2 sequence is critical to formation of the functional domain boundaries for this locus.
Functional domains are stretches of DNA within the genome that contain all the regulatory signals and other information necessary to activate or repress a particular gene. Each domain is an entity unto itself that is defined, or bracketed, by a boundary, much as words in a sentence are bracketed by punctuation marks. The researchers’ data suggest that repeated genomic sequences might be a widely used strategy used in mammals to organize functional domains.
“Without boundary elements, the coding portion of the genome is like a long, run-on sequence of words without punctuation,” said Rosenfeld.
Decoding the information written in “junk” DNA could open new areas of medical research, particularly in the area of gene therapy. Scientists may find that transferring encoding genes into a patient, without also transferring the surrounding genomic sequences which give structure or meaning to these genes, would render gene therapy ineffective.
Contributors to the paper include Lluis Montoliu, Rosa Roy and Angel Garcia-Díaz of the Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología in Madrid, Spain; Christopher K. Glass, M.D., Ph.D., UCSD Department of Cellular and Molecular Medicine; Esperanza Núñez, Gratien G. Prefontaine, Bong-Gun Ju, Kenneth A. Ohgi, Kasey Hutt, Xiaoyan Zhu and Yun Yung, Howard Hughes Medical Institute, Department of Molecular Medicine, UCSD School of Medicine; and Thorsten Cramer, Division of Endocrinology, UCSD Department of Medicine.
The research was funded in part by the Howard Hughes Medical Institute and the National Institutes of Health.
Contact: Debra Kain
University of California – San Diego
This release is also available in French.
Quebec City, July 12, 2007 – Dr. Philippe De Wals of Université Laval’s Department of Social and Preventive Medicine today publishes a study clearly indicating that the addition of folic acid to flours has led to a 46% drop in the incidence of congenital neural tube deformation (mainly anencephaly and spina bifida) in Canada. Such deformations either result in the child’s death or in major health problems, including physical and learning disabilities. Dr. De Wals’s work as head of a team of a dozen Canadian researchers appears today in the New England Journal of Medicine.
The neural tube is the basis of the embryo’s nervous system. Poor development of the neural tube, which is sometimes due to a lack of folic acid, can result in major health problems. Folic acid is found in green vegetables, fruit, whole grains, and meat. However, even a balanced diet won’t supply enough folic acid for a pregnant mother and the child she is carrying. Before1998, Canadian medical authorities were already recommending that women in their child-bearing years consume vitamin supplements containing folic acid. “Canada decided to add folic acid to all flour produced in the country because formation of the neural tube in embryos is particularly intense during the first four weeks of pregnancy, which is before a lot of women even know they’re pregnant. Since half of Canadian pregnancies are unplanned and the human body can’t store folic acid, it is better to integrate folic acid into the food chain than to focus exclusively on taking vitamin supplements,” stated Dr. De Wals. Health Canada still recommends taking folic acid supplements to women in their child-bearing years.
Researchers Dr. Philippe De Wals and Fassiatou Tairou of Université Laval’s Faculty of Medicine compared the incidence of neural tube deformations before and after the introduction of folic acid–enriched flours for over 2 million births in Canada. Between 1993 and 1997, the incidence was 1.58 per 1,000 births. Between 2000 and 2002, the rate dropped 46% to 0.86. The biggest improvement occurred in the parts of Canada that had the highest rates of neural tube deformation before 1998—Newfoundland, Prince Edward Island, and Nova Scotia. In Québec, the drop was also pronounced, but closer to the Canadian average.
Currently, only Canada, the United States, and Chile require that folic acid be added to flour. The effectiveness of this practice, as demonstrated by Dr. De Wals’s team, could encourage other countries to follow suit. Every year, approximately 200,000 cases of spina bifida and anencephaly occur worldwide. Adding folic acid to food could reduce that number by half.
Contact: Martin Guay
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