Atlas of palliative care across Europe unveiled

The standard of palliative care provided for those approaching the end of their lives varies greatly, according to the first comprehensive European overview of the service.

31 may 2013--Researchers, led by Professor David Clark from the University of Glasgow and Professor Carlos Centeno of the University of Navarra, Spain have compiled a European Atlas of provision which will be unveiled at the World Congress of Palliative Care, in Prague, May 30th – June 2nd 2013.

The Atlas offers a comprehensive overview of services, policies and strategies to improve end of life care in the 53 countries which make up the World Health Organisation's (WHO) European Region through a series of maps which chart the relationship in many countries between high Gross Domestic Product (GDP), Human Development Index (HDI) and indicators relating to health expenditure. The Atlas also contains detailed profiles of palliative care delivery in each country, with information updated from a previous study in 2007.

The team found that some countries, including the United Kingdom, Sweden and Iceland scored consistently high on all indicators, with the highest concentration of palliative care services per head of population found to be in Ireland, Belgium, Luxembourg and Sweden.

Although levels end of life provision were poorer in the former Communist block the research did conclude that Eastern European palliative care provision was generally good, in spite of the relatively lower standards of living in that part of the continent, with the Republic of Moldova, Romania and Poland noted as areas where a significant level of palliative care development has been reached.

Professor David Clark, who is Director of the Dumfries Campus and Head of the School of Interdisciplinary Studies at the University of Glasgow and a leading researcher in the field said that "As the population in Europe ages, there is a growing interest in palliative care and how individuals can be supported towards the end of life. This Atlas is a key tool to drive policy and practice across Europe and to assist in the development of new services."

Other significant findings since 2007 include:

• A substantial number of countries have achieved Specialty or Sub-specialty accreditation in Palliative Medicine (with a further number in process);
• There has been a significant increase in the integration of palliative care legislation into the health policy of many countries;
• The ´vitality´ of palliative care (identified national associations, published journals, related directories, attendees at conferences, etc.) has improved in the vast majority of European countries;
• Palliative care service provision for children continues to develop throughout the WHO European Region.

More information: The EAPC Atlas of Palliative Care in Europe 2013 Cartographic Edition is available to be viewed from issuu.com/universi… full_edition

For more information about the conference, go to eapc-2013.org/

Provided by University of Glasgow

Meta-analysis confirms common painkillers increase risk of heart problems and death

NSAIDs have been the cornerstone in managing pain in people with inflammatory disorders like rheumatoid arthritis, and are some of the most commonly used drugs worldwide. Earlier research has linked their use with an increased risk of serious gastrointestinal complications, while a new generation of NSAIDs (coxibs) developed to reduce these gastrointestinal side effects have come under scrutiny for increasing the risk of heart attacks and death.

30 may 2013--This new study now shows that higher dose regimens of older NSAIDs, such as diclofenac 150mg and ibuprofen 2400mg daily, are associated with similar risks of heart disease.

As such, for every 1000 individuals with a moderate risk of heart disease allocated to 1 year of treatment with high-dose diclofenac or ibuprofen, about three would experience an avoidable heart attack, of which one would be fatal.

In addition, all NSAIDs double the risk of heart failure and produce a 2-times increased risk of serious upper gastrointestinal complications such as bleeding ulcers.

The Coxib and traditional NSAID Trialists' (CNT) Collaboration combined data on outcomes of over 353 000 patients comparing one NSAID with another NSAID or placebo.

The meta-analysis of patient data from 639 randomised trials shows that the size of these risks can be predicted, which may help physicians decide which types of patient are best suited to which NSAID regimen.

Importantly, the increased risk of heart attacks from individual NSAIDs seemed to be proportional to a patient's underlying risk of such heart attacks, so that the risk is highest in those with a previous history of heart disease or those with cardiac risk factors such as raised blood pressure or cholesterol.

According to lead author Professor Colin Baigent from the Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK, "Whilst NSAIDs increase vascular and gastrointestinal risks to a varying extent, our analyses indicate that the effects of different regimens in particular patients can be predicted, which may help physicians choosing between alternative NSAID regimens to weigh up which type of NSAID is safest in different patients."

Writing in a linked Comment, Marie Griffin from Vanderbilt University Medical Center in the USA says, "The meta-analysis offers considerable certainty about relative and absolute major vascular risks of high doses of the most commonly prescribed NSAIDs, but leaves large gaps about risks associated with lower NSAID doses, longer durations of use, and residual effects after stopping treatment."

She adds, "Identification of safe and effective strategies for chronic pain is sorely needed. In the meantime, long-term use of high dose NSAIDs should be reserved for those who receive considerable symptomatic benefit from the treatment and understand the risks."

More information: www.thelancet.com/… 0-9/abstract

Provided by Lancet

Psychotherapy's benefits for depression

Treatments for depression that don't involve antidepressant drugs but rather focus on different forms of talking therapy (referred to as psychotherapeutic interventions) are all beneficial, with no one form of therapy being better than the others, according to a study by international researchers published in this week's PLOS Medicine.

29 may 2013--These findings are important as they suggest that patients with depression should discuss different forms of non-drug therapy with their doctors and explore which type of psychotherapy best suits them.

The researchers, led by Jürgen Barth from the University of Bern in Switzerland, reached these conclusions by reviewing 198 published studies involving over 15,000 patients receiving one of seven types of psychotherapeutic intervention: Interpersonal psychotherapy, behavioural activation, cognitive behavioural therapy, problem solving therapy, psychodynamic therapy, social skills training and supportive counselling.* The authors compared each of the therapies with each other and with a control—patients on a waiting list or continuing usual case—and combined the results.

The authors found that all seven therapies were better at reducing symptoms of depression than waiting list and usual care and that there were no significant differences between the different types of therapy. They also found that the therapies worked equally well for different patient groups with depression, such as for younger and older patients and for mothers who had depression after having given birth. Furthermore, the authors found no substantial differences when comparing individual with group therapy or with face-to-face therapy compared with internet-based interactions between therapist and patient.

The authors say: "We found evidence that most of the seven psychotherapeutic interventions under investigation have comparable effects on depressive symptoms and achieve moderate to large effects vis-à-vis waitlist."

They continue: "All seven psychotherapeutic interventions achieved a small to moderate effect compared to usual care."

The authors add: "Overall, we found that different psychotherapeutic interventions for depression have comparable, moderate-to-large effects."

*"Interpersonal psychotherapy" is short and highly structured, using a manual to focus on interpersonal issues in depression.

"Behavioral activation" raises the awareness of pleasant activities and seeks to increase positive interactions between the patient and his or her environment.

"Cognitive behavioural therapy" focuses on a patient's current negative beliefs, evaluates how they affect current and future behaviour, and attempts to restructure the beliefs and change the outlook. "Problem solving therapy" aims to define a patient's problems, propose multiple solutions for each problem, and then select, implement, and evaluate the best solution.

"Psychodynamic therapy" focuses on past unresolved conflicts and relationships and the impact they have on a patient's current situation.

In "social skills therapy," patients are taught skills that help to build and maintain healthy relationships based on honesty and respect.

"Supportive counselling" is a more general therapy that aims to get patients to talk about their experiences and emotions and to offer empathy without suggesting solutions or teaching new skills.

More information: Barth J, Munder T, Gerger H, Nu¨ esch E, Trelle S, et al. (2013) Comparative Efficacy of Seven Psychotherapeutic Interventions for Patients with Depression: A Network Meta-Analysis. PLoS Med 10(5): e1001454. doi:10.1371/journal.pmed.1001454

Provided by Public Library of Science

Scientists discover cinnamon compounds' potential ability to prevent Alzheimer's

Graduate student researcher Roshni George, left, and Don Graves, University of California, Santa Barbara, adjunct professor in the Department of Molecular, Cellular, and Developmental Biology, have found that certain compounds in cinnamon are showing some promise in the effort to fight Alzheimer's. Credit: UCSB

Cinnamon: Can the red-brown spice with the unmistakable fragrance and variety of uses offer an important benefit? The common baking spice might hold the key to delaying the onset of –– or warding off –– the effects of Alzheimer's disease.

28 may 2013--That is, according to Roshni George and Donald Graves, scientists at UC Santa Barbara. The results of their study, "Interaction of Cinnamaldehyde and Epicatechin with Tau: Implications of Beneficial Effects in Modulating Alzheimer'sDisease Pathogenesis," appears in the online early edition of the Journal of Alzheimer's Disease, and in the upcoming Volume 36, issue 1 print edition.

Alzheimer's disease is the most common form of dementia, a neurodegenerative disease that progressively worsens over time as it kills brain cells. No cure has yet been found, nor has the major cause of Alzheimer's been identified.

However, two compounds found in cinnamon –– cinnamaldehyde and epicatechin –– are showing some promise in the effort to fight the disease. According to George and Graves, the compounds have been shown to prevent the development of the filamentous "tangles" found in the brain cells that characterize Alzheimer's.

Responsible for the assembly of microtubules in a cell, a protein called tau plays a large role in the structure of the neurons, as well as their function.

"The problem with tau in Alzheimer's is that it starts aggregating," said George, a graduate student researcher. When for the protein does not bind properly to the microtubules that form the cell's structure, it has a tendency to clump together, she explained, forming insoluble fibers in the neuron. The older we get the more susceptible we are to these twists and tangles, Alzheimer's patients develop them more often and in larger amounts.

The use of cinnamaldehyde, the compound responsible for the bright, sweet smell of cinnamon, has proven effective in preventing the tau knots. By protecting tau from oxidative stress, the compound, an oil, could inhibit the protein's aggregation. To do this, cinnamaldehyde binds to two residues of an amino acid called cysteine on the tau protein. The cysteine residues are vulnerable to modifications, a factor that contributes to the development of Alzheimer's.

"Take, for example, sunburn, a form of oxidative damage," said Graves, adjunct professor in UCSB's Department of Molecular, Cellular, and Developmental Biology. "If you wore a hat, you could protect your face and head from the oxidation. In a sense this cinnamaldehyde is like a cap." While it can protect the tau protein by binding to its vulnerable cysteine residues, it can also come off, Graves added, which can ensure the proper functioning of the protein.

Oxidative stress is a major factor to consider in the health of cells in general. Through normal cellular processes, free radical-generating substances like peroxides are formed, but antioxidants in the cell work to neutralize them and prevent oxidation. Under some conditions however, the scales are tipped, with increased production of peroxides and free radicals, and decreased amounts of antioxidants, leading to oxidative stress.

Epicatechin, which is also present in other foods, such as blueberries, chocolate, and red wine, has proven to be a powerful antioxidant. Not only does it quench the burn of oxidation, it is actually activated by oxidation so the compound can interact with the cysteines on the tau protein in a way similar to the protective action of cinnamaldehyde.

"Cell membranes that are oxidized also produce reactive derivatives, such as Acrolein, that can damage the cysteines," said George. "Epicatechin also sequesters those byproducts."

Studies indicate that there is a high correlation between Type 2 diabetes and the incidence of Alzheimer's disease. The elevated glucose levels typical of diabetes lead to the overproduction of reactive oxygen species, resulting in oxidative stress, which is a common factor in both diabetes and Alzheimer's disease. Other research has shown cinnamon's beneficial effects in managing blood glucose and other problems associated with diabetes.

"Since tau is vulnerable to oxidative stress, this study then asks whether Alzheimer's disease could benefit from cinnamon, especially looking at the potential of small compounds," said George.

Although this research shows promise, Graves said, they are "still a long way from knowing whether this will work in human beings." The researchers caution against ingesting more than the typical amounts of cinnamon already used in cooking.

If cinnamon and its compounds do live up to their promise, it could be a significant step in the ongoing battle against Alzheimer's. A major risk factor for the disease –– age –– is uncontrollable. In the United States, Alzheimer's presents a particular problem as the population lives longer and the Baby Boom generation turns gray, leading to a steep rise in the prevalance of the disease. It is a phenomenon that threatens to overwhelm the U.S. health care system. According to the Alzheimer's Association, in 2013, Alzheimer's disease will cost the nation $203 billion.

"Wouldn't it be interesting if a small molecule from a spice could help?" commented Graves, "perhaps prevent it, or slow down the progression."

Provided by University of California - Santa Barbara

Hormone replacement therapy—clarity at last

The British Menopause Society and Women's Health Concern have today released updated guidelines on Hormone Replacement Therapy (HRT) to provide clarity around the role of HRT, the benefits and the risks. The new guidelines appear in the society's flagship title,Menopause International.

26 may 2013--Over the last 11 years, HRT has changed from being branded the "elixir of youth" to being considered extremely risky and only to be used in certain circumstances. Since the publication of the Women's Health Initiative (WHI) trial in 2002, and the Million Women study (MWS) in 2003, confusion and controversy has surrounded the use of HRT and the known benefits have often been forgotten.

A panel of experts have carefully considered, researched and reanalyzed the WHI and MWS studies alongside conducting further trials and studies, to offer practioners a detailed review of the evidence to help them optimize their clinical decisions, and provide women with more balanced and accurate advice on HRT treatment for menopause.

The new HRT recommendations are designed to complement the BMS Observations and Recommendations on menopause. The updated guidelines detail key recommendations targeting access to advice on how women can optimize their menopause transition and beyond, focusing in particular on lifestyle and diet and an opportunity to discuss the pros and cons of complementary therapies and HRT.

"Our aim is to provide helpful and pragmatic guidelines for health professionals involved in prescribing HRT and for women considering or currently using HRT" says Nick Panay, Chair of The British Menopause Society and lead author of the recommendations. "With these updated recommendations, it is hoped that HRT will once again be used appropriately and provide benefits for many women in their menopause."

More information: "The 2013 British Menopause Society & Women's Health Concern recommendations on hormone replacement therapy" by Nick Panay, Haitham Hamoda, Roopen Arya and Michael Sarvas on behalf of the British Menopause Society and Women's Health Concern, published by SAGE in Menopause International, June 2013.

Provided by SAGE Publications

Study identifies genes, pathways altered during relaxation response practice

A new study from investigators at the Benson-Henry Institute for Mind/Body Medicine at Massachusetts General Hospital (MGH) and Beth Israel Deaconess Medical Center (BIDMC) finds that elicitation of the relaxation response – a physiologic state of deep rest induced by practices such as meditation, yoga, deep breathing and prayer – produces immediate changes in the expression of genes involved in immune function, energy metabolism and insulin secretion. Published in the open-access journal PLOS ONE, the study combined advanced expression profiling and systems biology analysis to both identify genes affected by relaxation response practice and determine the potential biological relevance of those changes.

24 may 2013--"Many studies have shown that mind/body interventions like the relaxation response can reduce stress and enhance wellness in healthy individuals and counteract the adverse clinical effects of stress in conditions like hypertension, anxiety, diabetes and aging," says Herbert Benson, MD, director emeritus of the Benson-Henry Institute and co-senior author of the PLOS ONE report. "Now for the first time we've identified the key physiological hubs through which these benefits might be induced."

Towia Libermann, PhD – director of the Beth Israel Deaconess Medical Center (BIDMC) Genomics, Proteomics, Bioinformatics and Systems Biology Center and co-senior author of the study – adds, "Some of the biological pathways we identify as being regulated by relaxation response practice are already known to play specific roles in stress, inflammation and human disease. For others, the connections are still speculative, but this study is generating new hypotheses for further investigation."

Benson first described the relaxation response – the physiologic opposite of the fight-or-flight response – almost 40 years ago, and his team has pioneered the application of mind/body techniques to a wide range of health problems. Studies in many peer-reviewed journals have documented how the relaxation response both alleviates symptoms of anxiety and many other disorders and also affects factors such as heart rate, blood pressure, oxygen consumption and brain activity. In 2008, Benson and Libermann led a study finding that long-term practice of the relaxation response changed the expression of genes involved with the body's response to stress. The current study examined changes produced during a single session of relaxation response practice, as well as those taking place over longer periods of time.

The study enrolled a group of 26 healthy adults with no experience in relaxation response practice, who then completed an 8-week relaxation response training course. Prior to starting their training, the participants went through what was essentially a control group session – blood samples were taken before and immediately after they listened to a 20-minute health education CD and again 15 minutes later. After completing the training course, a similar set of blood tests was taken before and after participants listened to a 20-minute CD used to elicit the relaxation response as part of daily practice.

The sets of blood tests taken before the training program were designated "novice," and those taken after training completion were categorized as from "short-term practitioners." For further comparison a similar set of blood samples was taken from a group of 25 individuals with 4 to 25 years experience regularly eliciting the relaxation response through many different techniques before and after they listened to the same relaxation response CD. Blood samples from all participants were analyzed to determine the expression of more than 22,000 genes at the different time points.

The results revealed significant changes in the expression of several important groups of genes between the novice samples and those from both the short- and long-term sets, with even more pronounced changes in the long-term practitioners. A systems biology analysis of known interactions among the proteins produced by the affected genes revealed that pathways involved with energy metabolism, particularly the function of mitochondria, were upregulated during the relaxation response. Pathways controlled by activation of a protein called NF-κB – known to have a prominent role in inflammation, stress, trauma and cancer – were suppressed after relaxation response elicitation. The expression of genes involved in insulin pathways was also significantly altered.

"The combination of genomics and systems biology in this study provided great insight into the key molecules and physiological gene interaction networks that might be involved in relaying beneficial effects of relaxation response in healthy subjects," says Manoj K. Bhasin, PhD, co-lead author of the study and co-director of the BIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Center. He notes that these insights should provide a framework for determining, on a genomic basis, whether the relaxation response will help alleviate symptoms of diseases triggered by stress and developing biomarkers that may suggest how individual patients will respond to interventions.

Benson stresses that the long-term practitioners in this study elicited the relaxation response through many different techniques – various forms of meditation, yoga or prayer – but those differences were not reflected in the gene expression patterns. "People have been engaging in these practices for thousands of years, and our finding of this unity of function on a basic-science, genomic level gives greater credibililty to what some have called 'new age medicine,' " he says.

Libermann says, "While this and our previous studies focused on healthy participants, we currently are studying how the genomic changes induced by mind/body interventions affect pathways involved in hypertension, inflammatory bowel disease and irritable bowel syndrome. We have also started a study – a collaborative undertaking between the Dana Farber Cancer Institute, the Massachusetts General Hospital and the Beth Israel Deaconess Medical Center – in patients with precursor forms of multiple myeloma, a condition known to involve activation of NF-κB pathways."

Provided by Massachusetts General Hospital

Calcium supplements linked to longer lifespans in women

Taking a calcium supplement of up to 1,000 mg per day can help women live longer, according to a recent study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM).

23 may 2013--Calcium, an essential nutrient for bone health, is commonly found in dairy products as well as vitamins. Although calcium is an essential nutrient for bone health, past studies have linked calcium supplements to heart disease risk. Researchers analyzing data from the large-scale Canadian Multicentre Osteoporosis Study (CaMos) sought to clarify this issue and found moderate doses of calcium supplements had a beneficial effect in women.

"Our study found daily use of calcium supplements was associated with a lower risk of death among women," said the study's lead author, David Goltzman, MD, of McGill University in Montreal, Canada. "The benefit was seen for women who took doses of up to 1,000 mg per day, regardless of whether the supplement contained vitamin D."

The longitudinal cohort study monitored the health of 9,033 Canadians between 1995 and 2007. During that period, 1,160 participants died. Although the data showed women who took calcium supplements had a lower mortality risk, there was no statistical benefit for men. The study found no conclusive evidence that vitamin D had an impact on mortality.

"Higher amounts of calcium were potentially linked to longer lifespans in women, regardless of the source of the calcium," Goltzman said. "That is, the same benefits were seen when the calcium came from dairy foods, non-dairy foods or supplements."

More information: The article, "Calcium and Vitamin D Intake and Mortality: Results from the Canadian Multi-centre Osteoporosis Study," will appear in the July 2013 issue of JCEM.

Provided by The Endocrine Society

The compound in the Mediterranean diet that makes cancer cells 'mortal'

New research suggests that a compound abundant in the Mediterranean diet takes away cancer cells' "superpower" to escape death. By altering a very specific step in gene regulation, this compound essentially re-educates cancer cells into normal cells that die as scheduled.

21 mau 2013--One way that cancer cells thrive is by inhibiting a process that would cause them to die on a regular cycle that is subject to strict programming. This study in cells, led by Ohio State University researchers, found that a compound in certain plant-based foods, called apigenin, could stop breast cancer cells from inhibiting their own death.

Much of what is known about the health benefits of nutrients is based on epidemiological studies that show strong positive relationships between eating specific foods and better health outcomes, especially reduced heart disease. But how the actual molecules within thesehealthful foods work in the body is still a mystery in many cases, and particularly with foods linked to lower risk for cancer.

Parsley, celery and chamomile tea are the most common sources of apigenin, but it is found in many fruits and vegetables.

The researchers also showed in this work that apigenin binds with an estimated 160 proteins in the human body, suggesting that other nutrients linked to health benefits – called "nutraceuticals" – might have similar far-reaching effects. In contrast, most pharmaceutical drugs target a single molecule.

"We know we need to eat healthfully, but in most cases we don't know the actual mechanistic reasons for why we need to do that," said Andrea Doseff, associate professor of internal medicine and molecular genetics at Ohio State and a co-lead author of the study. "We see here that the beneficial effect on health is attributed to this dietary nutrient affecting many proteins. In its relationship with a set of specific proteins, apigenin re-establishes the normal profile in cancer cells. We think this can have great value clinically as a potential cancer-prevention strategy."

Doseff oversaw this work with co-lead author Erich Grotewold, professor of molecular genetics and director of Ohio State's Center for Applied Plant Sciences (CAPS). The two collaborate on studying the genomics of apigenin and other flavonoids, a family of plant compounds that are believed to prevent disease.

The research appears this week in the online early edition of the journal Proceedings of the National Academy of Sciences.

Though finding that apigenin can influence cancer cell behavior was an important outcome of the work, Grotewold and Doseff point to their new biomedical research technique as a transformative contribution to nutraceutical research.

They likened the technique to "fishing" for the human proteins in cells that interact with small molecules available in the diet.

"You can imagine all the potentially affected proteins as tiny fishes in a big bowl. We introduce this molecule to the bowl and effectively lure only the truly affected proteins based on structural characteristics that form an attraction," Doseff said. "We know this is a real partnership because we can see that the proteins and apigenin bind to each other."

Through additional experimentation, the team established that apigenin had relationships with proteins that have three specific functions. Among the most important was a protein called hnRNPA2.

This protein influences the activity of messenger RNA, or mRNA, which contains the instructions needed to produce a specific protein. The production of mRNA results from the splicing, or modification, of RNA that occurs as part of gene activation. The nature of the splice ultimately influences which protein instructions the mRNA contains.

Doseff noted that abnormal splicing is the culprit in an estimated 80 percent of all cancers. In cancer cells, two types of splicing occur when only one would take place in a normal cell – a trick on the cancer cells' part to keep them alive and reproducing.

In this study, the researchers observed that apigenin's connection to the hnRNPA2 protein restored this single-splice characteristic to breast cancer cells, suggesting that when splicing is normal, cells die in a programmed way, or become more sensitive to chemotherapeutic drugs.

"So by applying this nutrient, we can activate that killing machinery. The nutrient eliminated the splicing form that inhibited cell death," said Doseff, also an investigator in Ohio State's Davis Heart and Lung Research Institute. "Thus, this suggests that when we eat healthfully, we are actually promoting more normal splice forms inside the cells in our bodies."

The beneficial effects of nutraceuticals are not limited to cancer, as the investigators previously showed that apigenin has anti-inflammatory activities.

The scientists noted that with its multiple cellular targets, apigenin potentially offers a variety of additional benefits that may even occur over time. "The nutrient is targeting many players, and by doing that, you get an overall synergy of the effect," Grotewold explained.

Doseff is leading a study in mice, testing whether food modified to contain proper doses of this nutrient can change splicing forms in the animals' cells and produce an anti-cancer effect.

More information: Molecular basis for the action of a dietary flavonoid revealed by the comprehensive identification of apigenin human targets, www.pnas.org/cgi/d… s.1303726110

Provided by The Ohio State University

Individuals who drink heavily and smoke may show 'early aging' of the brain

Treatment for alcohol use disorders works best if the patient actively understands and incorporates the interventions provided in the clinic. Multiple factors can influence both the type and degree of neurocognitive abnormalities found during early abstinence, including chronic cigarette smoking and increasing age. A new study is the first to look at the interactive effects of smoking status and age on neurocognition in treatment-seeking alcohol dependent (AD) individuals. Findings show that AD individuals who currently smoke show more problems with memory, ability to think quickly and efficiently, and problem-solving skills than those who don't smoke, effects which seem to become exacerbated with age.

20 may 2013--Results will be published in the October 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"Several factors – nutrition, exercise, comorbid medical conditions such as hypertension and diabetes, psychiatric conditions such as depressive disorders and post-traumatic stress disorder, and genetic predispositions – may also influence cognitive functioning during earlyabstinence," explained Timothy C. Durazzo, assistant professor in the department of radiology and biomedical imaging at the University of California San Francisco, and corresponding author for the study. "We focused on the effects of chronic cigarette smoking and increasing age on cognition because previous research suggested that each has independent, adverse affects on multiple aspects of cognition and brain biology in people with and without alcohol use disorders. This previous research also indicated that the adverse effects of smoking on the brain accumulate over time. Therefore, we predicted that AD, active chronic smokers would show the greatest decline in cognitive abilities with increasing age."

"The independent and interactive effects of smoking and other drug use on cognitive functioning among individuals with AD are largely unknown," added Alecia Dager, associate research scientist in the department of psychiatry at Yale University. "This is problematic because many heavy drinkers also smoke. Furthermore, in treatment programs for alcoholism, the issue of smoking may be largely ignored. This study provides evidence of greater cognitive difficulties in alcoholics who also smoke, which could offer important insights for treatment programs. First, individuals with AD who also smoke may have more difficulty remembering, integrating, and implementing treatment strategies. Second, there are clear benefits for thinking skills as a result of quitting both substances."

Durazzo and his colleagues compared the neurocognitive functioning of four groups of participants, all between the ages of 26 and 71 years of age: never-smoking healthy individuals or "controls" (n=39); and one-month abstinent, treatment-seeking AD individuals, who were never-smokers (n = 30), former-smokers (n = 21) and active-smokers (n = 68). Evaluated cognitive abilities included cognitive efficiency, executive functions, fine motor skills, general intelligence, learning and memory, processing speed, visuospatial functions, and working memory.

"We found that, at one month of abstinence, actively smoking AD [individuals] had greater-than-normal age effects on measures of learning, memory, processing speed, reasoning and problem-solving, and fine motor skills," said Durazzo. "AD never-smokers and former-smokers showed equivalent changes on all measures with increasing age as the never-smoking controls. These results indicate the combination of alcohol dependence and active chronic smoking was related to an abnormal decline in multiple cognitive functions with increasing age."

"These results indicate the combined effects of these drugs are especially harmful and become even more apparent in older age," said Dager. "In general, people show cognitive decline in older age. However, it seems that years of combined alcohol and cigarette use exacerbate this process, contributing to an even greater decline in thinking skills in later years."

Durazzo agreed. "Chronic cigarette smoking, excessive alcohol consumption, and increasing age are all associated with increased oxidative damage to brain tissue," he said. "Oxidative damage results from increased levels of free radicals and other compounds that directly injure neurons and other cells that make up the brain. Cigarette smoking and excessive alcohol consumption expose the brain to a tremendous amount of free radicals. We hypothesize that chronic, long-term exposure to cigarette smoke and excessive alcohol consumption interacts with the normal aging process to produce greater neurocognitive decline in the active-smoking AD group."

Cigarette smoking is a "modifiable health risk" that is directly associated with at least 440,000 deaths every year in the United States, Durazzo noted. "Chronic smoking, and to a lesser extent, alcohol use disorders are also associated with an increased risk for Alzheimer's disease," he said. "So, the combination of these modifiable health risks may place an individual at even greater risk for development of Alzheimer's disease. Given the above, in conjunction with the findings from our cognitive and neuroimaging research, we completely support programs that routinely offer smoking cessation programs to all individuals seeking treatment for alcohol/substance abuse disorders."

US psychiatry gets makeover in new manual

The latest makeover to a massive psychiatric tome honored by some, reviled by others and even called the "Bible" of mental disorders is being released Saturday with a host of new changes.

19 may 2013--The first major revamp in more than 20 years of the Diagnostic and Statistical Manual of Mental Disorders, or DSM-5, will be unveiled in San Francisco at the annual meeting of the American Psychiatry Association.

Hoarding, gambling and marijuana withdrawal are among the newly expanded disorders contained in the fifth revision of the 947-page reference book.

Other categories have been redesigned, such as autism spectrum disorder, which is now the sole title for a range of previously separate diagnoses that used to include Asperger's, autistic and childhood disintegrative disorder.

The revision is based on new insights from research since the last version of the manual was published in 1990.

The book offers experts a common language for diagnosing mental disorders, and can play a role in what health insurance covers and does not.

The director of the National Institute of Mental Health, Thomas Insel, acknowledged that many of the changes were "contentious" but said "the final product involves mostly modest alterations of the previous edition."

However, the book and its changes have generated plenty of controversy, with critics saying it has the power to make certain common struggles into diagnosable disorders, possibly leading to overmedication of the population.

An early version of the DSM manual described homosexuality as a mental disorder, but that was eliminated in 1973.

In the new version, post-traumatic stress disorder will no longer be considered an anxiety disorder but will be classed under the chapter on trauma and stressor-related disorders.

In a bid to reduce incorrect diagnoses and prescriptions of anti-psychotic medication to children as young as two, the manual has created a new category for "disruptive mood dysregulation disorder," for hostility and outbursts beyond regular tantrums but not to the level of bipolar disorder.

Other changes include the removal of the grief-exclusion, which had said that people who have lost a loved one were not to be diagnosed with major depression, meaning the newly bereaved can now be diagnosed as depressed.

Gambling addiction is now included in the Substance Use Disorders chapter for the first time, and marijuana withdrawal will be considered a symptom of addictive disease.

Attention deficit hyperactivity disorder has been changed to include youths who show symptoms before age 12 instead of seven, and in adults five symptoms are required for diagnosis instead of six.

"Later age of onset and reduction in symptom counts in adults should lead to more accurate diagnosis," said Jeffrey Newcorn, director of the Division of Child and Adolescent Psychiatry at Mount Sinai Hospital.

"Although there will no doubt be concerns that the new criteria will lead to an increase in prevalence rates, the revised criteria should better align with clinical realities and support best treatment practices."

Obsessive-compulsive disorder has its own category for the first time, and includes the new hoarding disorder as well as body dysmorphic disorder and trichotillomania, or hair-pulling, which used to be considered impulse-control disorders.

Even though the DSM has generated plenty of discussion, the top US mental health official said its days as a guide for the psychiatry field may be nearing an end.

"While DSM has been described as a 'Bible' for the field, it is, at best, a dictionary, creating a set of labels and defining each," Insel wrote in a blog post in late April.

He said the focus of research should be on emerging research, not on the symptom clusters outlined in the DSM's categories.

"In the rest of medicine, this would be equivalent to creating diagnostic systems based on the nature of chest pain or the quality of fever," he wrote. "Symptoms alone rarely indicate the best course of treatment."

© 2013 AFP

Routine screening for depression not recommended for adults with no apparent symptoms of depression

For adults with no apparent symptoms of depression, routine screening is not recommended in primary care settings because of the lack of high-quality evidence on the benefits and harms of screening for depression, according to new evidence-based guidelines from the Canadian Task Force on Preventive Health Care (CTFPHC) published in CMAJ (Canadian Medical Association Journal).

18 may 2013--These guidelines mark a change in approach from the task force's 2005 guidelines, which recommended screening adults in primary care settings where there were integrated staff-assisted systems to manage treatment.

"In the absence of a demonstrated benefit of screening, and in consideration of the potential harms, we recommend not routinely screening for depression in primary care settings, either in adults at average risk or in those with characteristics that may increase their risk of depression," writes Dr. Michael Joffres, chair of the CTFPHC's depression guideline writing group and member of the Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, with coauthors.

The recommendations do not apply to people with known depression, with a history of depression or who are receiving treatment for depression.

Key recommendations: 

• No routine screening in primary care settings for adults at average risk of depression.
• No routine screening in primary care settings for adults in subgroups of the population who may be at increased risk of depression, including people with a family history of depression, traumatic experiences as a child, recent traumatic life events, chronic health issues, substance abuse, perinatal and postpartum status, or Aboriginal origin.

However, clinicians should be alert to the possibility of depression, especially in patients with characteristics that may increase their risk of depression, and should look for it when there are clinical clues, such as insomnia, low mood, anhedonia (inability to experience pleasure) andsuicidal thoughts.

Guidelines in other countries differ slightly from the Canadian guidelines. The US Preventive Services Task Force recommends universal screening where supports exist to ensure follow-up treatment. In the United Kingdom, the National Institutes for Health and Clinical Excellence recommends a targeted approach, focusing on people with a history of depression rather than general screening.

These recommendations do not apply to people with known depression, with a history of depression or who are receiving treatment for depression.

"These recommendations do not apply to people with known depression, with a history of depression or who are receiving treatment for depression. Patients who present with symptoms or other clues to the presence of depression should be appropriately assessed for depression," explained Dr. Gabriela Lewin, member of the CTFPHC working group.

The task force calls for high-quality randomized controlled trials with an unscreened control group to understand the effect of screening, the potential harms of screening, such as false-positive diagnoses with subsequent unnecessary treatment, as well as the implications of earlier detection of depression through screening.

In a related commentary, Dr. Roger Bland, Department of Psychiatry, University of Alberta, and coauthor write, "There is no question, as the task force amply illustrates, that depression constitutes a major public health problem. Although milder cases may require only watchful waiting rather than treatment, about 15% of people with major depression go on to a chronic course, with much residual disability. Family physicians have been criticized for failing to recognize depression. However, studies have shown that many missed cases are those of milder depression, which often remits spontaneously, and that patients with milder forms of depression may experience adverse effects and other complications if the depression is treated."

More information: In addition to the full guidelines, a decision support tool and frequently asked questions for clinicians are available on the task force's website: www.canadiantaskforce.ca

Guidelines www.cmaj.ca/lookup… /cmaj.130403 
Commentary www.cmaj.ca/lookup… /cmaj.130634

Provided by Canadian Medical Association Journal

What is BRCA1? 

American actress Angelina Jolie has had a double mastectomy because she carries the faulty gene BRCA1.

Actress Angelina Jolie has today written an op-ed in the New York Times explaining that she has opted to have a double mastectomy because she carries the hereditary BRCA1 gene, which she says increases her risk of breast cancer by 87%. Her mother died from cancer after a ten-year struggle at the age of 56.

15 may 2013--We asked an expert in breast cancer and genetics to explain more about the breast cancer genetic mutation and what it means for women.

What are the BRCA1 (and BRCA2) gene mutations?

BRCA1 and BRCA2 are genes that have been linked to hereditary breast and ovarian cancer. Women who inherit one of these faulty genes are at an increased risk of breast or ovarian cancer. Men who inherit a faulty gene may be at increased risk of prostate cancer. Breast cancer in men carrying BRCA2 has also been described in the medical literature.

These genes are important in helping repair breaks in the DNA in our cells, so a faulty gene can mean that DNA repair is less than optimal. In some people this can lead to the development of cancer.

Should I be getting tested for them?

Not routinely. In general terms, genetic testing should be carried out following counselling in a familial cancer centre after a proper assessment of risk.

Testing is offered to people who have developed breast or ovarian cancer where there are features that might suggest a mutation is present.

These can include an early age of onset of cancer, or cancer in both breasts, multiple cancers in the family, male breast cancer, ovarian cancer, certain ancestry (such eastern European Jewish ancestry), or where there is a known mutation in the family.

Sometimes the appearance of a tumour, reported by the pathologist can help make a decision regarding whether testing is necessary.

How are they tested for?

This is generally done through a blood sample.

What is the cost of the test/s and why?

At present testing for these genes in Australia is expensive – about A$2,000 to A$2,500 – but costs are coming down.

Once a mutation has been identified in a family member, other members can be tested and this is much cheaper.

In Australia, the test is offered for free in familial cancer centres where a person meets suitable criteria for testing.

How many people are affected?

About 5% of all breast cancers are hereditary, and can involve the BRCA1 or BRCA2 gene. That is why it is important to look for special features that suggest risk.

In our community the risk of carrying a gene is relatively rare at about 1:800 for each of the mutations.

Say I have the gene/s, what is the likelihood that I will develop (a) breast cancer and (b) ovarian cancer?

Having the gene does not mean that a woman will definitely develop either of the cancers.

The risk is believed to be on average somewhere between 40% and 65% for breast and 15% to 40% for ovary, depending on the gene.

In her op-ed, Angelina Jolie said her risk of developing breast cancer was 87% and that she had a 50% risk of developing ovarian cancer. This is because the risk for BRCA1 carriers can be higher than for BRCA2 carriers.

Jolie has reported the upper end of risk for breast cancer that was first described when the gene was discovered. Looking at the general population, the risk is probably less, but for some families with very striking family histories, it could be this high.

What are the treatment options?

If a cancer develops, it is often treated in a very similar fashion to other breast or ovarian cancers.

For breast cancer, sometimes women might consider more extensive surgery (such as mastectomies). There are new drugs called PARP inhibitors that are being developed tested for BRCA-associated cancers.

What are the prevention options?

There are a number of options. For breast cancer, this includes close monitoring which includes MRI scans and mammograms starting at a suitable age.

Breast cancer prevention drugs such as Tamoxifen are likely to be helpful and may even halve the risk of getting breast cancer.

Some women may consider mastectomy with breast reconstruction. The uptake of this option differs; on average about 20% of women carrying the genes take this option in Australia but the precise numbers are not known.

Importantly, due to the potential risk of ovarian cancer some women will be advised to have their fallopian tubes and ovaries removed at a suitable age (and after they have had children).

If this is carried out at age 40, it can halve breast cancer risk. It is known to be safe to give women hormone replacement therapy in most cases, so that they don't experience menopausal symptoms.

What are the side-effects of mastectomies, if any?

These are generally minimal. In the short term, there can be surgical risks of infection and bleeding and, of course, cosmetic results (breast reconstruction) may differ.

What are the chances of survival for preventative measures vs treatment options?

The chances of survival for preventative measures are excellent and the risk of breast cancer is very substantially reduced. Since screening can detect cancer early, this helps improve outcomes.

Treatment for breast cancer has substantially improved over the last two decades, including for BRCA1 and BRCA2-associated cancers, so with proper treatment of early cancers, the outlook can be very good.

Source: The Conversation

This story is published courtesy of The Conversation (under Creative Commons-Attribution/No derivatives).

Study examines cognitive impairment in families with exceptional longevity

A study by Stephanie Cosentino, Ph.D., of Columbia University, New York, and colleagues examines the relationship between families with exceptional longevity and cognitive impairment consistent with Alzheimer disease.

13 may 2013--The cross-sectional study included a total of 1,870 individuals (1,510 family members and 360 spouse controls) recruited through the Long Life Family Study. The main outcome measure was the prevalence of cognitive impairment based on a diagnostic algorithm validated using the National Alzheimer's Coordinating Center data set.

According to study results, the cognitive algorithm classified 546 individuals (38.5 percent) as having cognitive impairment consistent with Alzheimer disease. Long Life Family Study probands had a slightly but not statistically significant reduced risk of cognitive impairment compared with spouse controls (121 of 232 for probands versus 45 of 103 for spouse controls), whereas Long Life Family Study sons and daughters had a reduced risk of cognitive impairment (11 of 213 for sons and daughters versus 28 of 216 for spouse controls). Restriction to nieces and nephews in the offspring generation attenuated this association (37 of 328 for nieces and nephews versus 28 of 216 for spouse controls).

"Overall, our results appear to be consistent with a delayed onset of disease in long-lived families, such that individuals who are part of exceptionally long-lived families are protected but not later in life," the study concludes.

More information: JAMA Neurol. Published online May 6, 2013. doi:10.1001/.jamaneurol.2013.1959

Provided by The JAMA Network Journals

Sunshine could benefit health and prolong life, study suggests

Exposing skin to sunlight may help to reduce blood pressure, cut the risk of heart attack and stroke – and even prolong life, a study suggests.

12 may 2013--Researchers have shown that when our skin is exposed to the sun's rays, a compound is released in our blood vessels that helps lower blood pressure.

The findings suggest that exposure to sunlight improves health overall, because the benefits of reducing blood pressure far outweigh the risk of developing skin cancer.

The study has been carried out by the University of Edinburgh.

Heart disease and stroke linked to high blood pressure are estimated to lead to around 80 times more deaths than those from skin cancer, in the UK.

Production of this pressure-reducing compound – called nitric oxide – is separate from the body's manufacture of vitamin D, which rises after exposure to sunshine. Until now it had been thought to solely explain the sun's benefit to human health, the scientists add.

The landmark proof-of-principle study will be presented on Friday in Edinburgh at the world's largest gathering of skin experts.

Researchers studied the blood pressure of 24 volunteers who sat beneath tanning lamps for two sessions of 20 minutes each. In one session, the volunteers were exposed to both the UV rays and the heat of the lamps. In the other, the UV rays were blocked so that only the heat of the lamps affected the skin.

The results showed that blood pressure dropped significantly for one hour following exposure to UV rays, but not after the heat-only sessions. Scientists say that this shows that it is the sun's UV rays that lead to health benefits. The volunteers' vitamin D levels remained unaffected in both sessions.

Dr Richard Weller, Senior Lecturer in Dermatology at the University of Edinburgh, said: "We suspect that the benefits to heart health of sunlight will outweigh the risk of skin cancer. The work we have done provides a mechanism that might account for this, and also explains why dietary vitamin D supplements alone will not be able to compensate for lack of sunlight.

"We now plan to look at the relative risks of heart disease and skin cancer in people who have received different amounts of sun exposure. If this confirms that sunlight reduces the death rate from all causes, we will need to reconsider our advice on sun exposure."

More information: The International Investigative Dermatology conference starts tomorrow (Wednesday) and runs until Saturday.

Provided by University of Edinburgh

PARKINSON: Unleashing the watchdog protein

McGill University researchers have unlocked a new door to developing drugs to slow the progression of Parkinson's disease. Collaborating teams led by Dr. Edward A. Fon at the Montreal Neurological Institute and Hospital -The Neuro, and Dr. Kalle Gehring in the Department of Biochemistry at the Faculty of Medicine, have discovered the three-dimensional structure of the protein Parkin.

11 may 2013--Mutations in Parkin cause a rare hereditary form of Parkinson's disease and are likely to also be involved in more commonly occurring forms of Parkinson's disease. The Parkin protein protects neurons from cell death due to an accumulation of defective mitochondria. Mitochondria are the batteries in cells, providing the power for cell functions. This new knowledge of Parkin's structure has allowed the scientists to design mutations in Parkin that make it better at recognizing damaged mitochondria and therefore possibly provide better protection for nerve cells.

The research will be published online May 9 in the leading journal Science.

"The majority of Parkinson's patients suffer from a sporadic form of the disease that occurs from a complex interplay of genetic and environmental factors which are still not fully understood, explains Dr. Fon, neurologist at The Neuro and head of the McGill Parkinson Program, a National Parkinson Foundation Centre of Excellence. "A minority of patients have genetic mutations in genes such as Parkin that cause the disease. Although there are differences between the genetic and sporadic forms, there is good reason to believe that understanding one will inform us about the other. It's known that toxins that poison mitochondria can lead to Parkinson's-like symptoms in humans and animals. Recently, Parkin was shown to be a key player in the cell's system for identifying and removing damaged mitochondria."

Researchers have unlocked a new door to developing drugs to slow the progression of Parkinson's disease. They have discovered the 3-D structure of the protein Parkin. Mutations in Parkin cause a rare hereditary form of Parkinson's disease and are likely to also be involved in more commonly occurring forms of Parkinson's disease. This new knowledge of Parkin's structure has allowed the scientists to design mutations in Parkin that make it better at recognizing damaged mitochondria and therefore possibly provide better protection for nerve cells. Credit: Montreal Neurological Institute and Hospital

Dr. Gehring, head of McGill's structural biology centre, GRASP, likens Parkin to a watchdog for damaged mitochondria. "Our structural studies show that Parkin is normally kept in check by a part of the protein that acts as a leash to restrict Parkin activity. When we made mutations in this specific 'leash' region in the protein, we found that Parkin recognized damaged mitochondria more quickly. If we can reproduce this response with a drug rather than mutations, we might be able to slow the progression of disease in Parkinson's patients."

Parkin is an enzyme in cells that attaches a small protein, ubiquitin, to other proteins to mark them for degradation. For example, when mitochondria are damaged, Parkin is switched on which leads to the clearing of the dysfunctional mitochondria. This is an important process because damaged mitochondria are a major source of cellular stress and thought to play a central role in the death of neurons in neurodegenerative diseases.

Husband and wife team, Drs. Jean-François Trempe and Véronique Sauvé, are lead authors on the paper. Dr. Sauvé led the Gehring team that used X-ray crystallography to determine the structure of Parkin. Dr. Trempe in the Fon laboratory directed the functional studies of Parkin.

"We are proud to invest in scientific excellence and to fund discovery stage research so that investigators like Dr. Gehring and Fon in Canada can test new theories and pursue promising new leads. We believe that our National Research Program plays an important role in the global search for better treatments and a cure for Parkinson's disease," says Joyce Gordon, President and CEO, Parkinson Society Canada.

More information: www.sciencemag.org… ence.1237908

Provided by McGill University

The Lancet Series on bipolar disorder

Bipolar disorder – where patients experience recurrent episodes of mood disturbance, ranging from extreme elation (mania) to severe depression – is thought to affect roughly 2% of the world's population in its most pronounced forms (bipolar I and II), with milder forms of the disorder affecting another 2%. A new Lancet Series provides a comprehensive overview of the genetics, diagnosis, and treatment of bipolar disorder, outlining future challenges, and debating imminent changes to the criteria that psychiatrists use to diagnose the illness.

10 may 2013--According to a Lancet Editorial accompanying the Series, "Bipolar disorder is not just about the extremes of emotion: it is also about the individual who exists both at, and between, those extremes. The psychiatrist of the future must be able to ally human and scientific understanding; to collaborate meaningfully and respectfully with patients in planning care; and to be confident and pragmatic, but receptive to new discoveries that may challenge the very basis of his or her understanding of mental illness. Psychiatry demands exceptional doctors."

Series paper 1 – Scientists may be on verge of identifying biological mechanisms that lead to bipolar disorder

Bipolar disorder is currently diagnosed purely on the basis of clinical symptoms, typically presenting as alternating periods of depression and mania. These episodes may differ in severity and may be accompanied by other symptoms such as hallucination and delusions. However, there is now compelling evidence that genes affect predisposition to bipolar disorder, and the authors of the first Series paper review current knowledge in this area.

While the contribution of environmental and social factors towards an individual's risk of developing bipolar disorder should not be underestimated, scientists' growing knowledge of the contribution of genetics to bipolar disorder nonetheless leads to the tantalising possibility that scientists might be on the verge of being able to identify some of the biological systems that lead to illness in bipolar disorder, which could in turn lead to substantial improvements in diagnosis and treatment of the illness.

According to Professor Nick Craddock, one of the paper's authors, "The association between genotype and phenotype for psychiatric disorders is clearly complex. Reductionist thinking has no place, and to think of any case as being either genetic or environmental, or to talk about a gene for bipolar disorder, makes no sense. The key point is that most cases of bipolar disorder involve the interplay of several genes or more complex genetic mechanisms, together with the effects of the environment, and chance."

The authors emphasise that bipolar disorder research now needs to follow up genetic studies with imaging and psychological studies, to try to unravel the complex biological mechanisms involved in bipolar disorder, and bring biological understanding closer to the experience of the patient. While several genes which increase a patient's risk of acquiring bipolar disorder have been discovered, to date, no clear biological mechanism to explain why these genes affect a person's risk of developing bipolar has been elucidated.

Series Paper 2 – Neuroimaging research could transform bipolar diagnosis

The second Series paper outlines the substantial difficulties in diagnosing bipolar disorder: misdiagnosis of bipolar as unipolar depression is thought to occur in many patients seeking treatment for depression, and there is an average delay of 5 – 10 years between the onset of bipolar disorder and diagnosis. Depressive symptoms are considerably more prevalent than manic symptoms over the course of the illness for most people with bipolar disorder, and people are more likely to seek treatment for depressive symptoms.

Evidence suggests that a proportion of people diagnosed with unipolar depression may, in fact, have bipolar disorder, and this can be a major problem, because medication used to treat unipolar depression is not the same as that used to treat bipolar disorder, and medicine for unipolar depression could even exacerbate the manic symptoms seen in bipolar.

According to Professor Mary Phillips, one of the paper's authors, "Identifying objective biomarkers that differ between bipolar and unipolar depression would not only lead to more accurate diagnosis but potentially to new, personalised treatments, yet very little research has been undertaken in this area. For instance, very few neuroimaging studies have been done in which the brains of people with bipolar disorder have been compared to those of people with unipolar disorder, and further research into this area is urgently needed."

Series paper 3 – Search for new treatments for bipolar is being hampered by scarce knowledge of basic disease mechanisms

There have been no fundamental advances in the search for more effective treatment for bipolar disorder in the last twenty years, despite a substantial expansion of research into the subject. The authors of the third Series paper point out that development of effective treatments is being hampered by scarce knowledge of basic disease mechanisms or clear targets for medicines.

Treating bipolar is complex, because the same treatments that alleviate depression can cause mania or mood swings, and treatments that reduce mania might cause rebound depressive episodes. While antidepressants are commonly used to treat the depressive phase of the disorder, there is scarce evidence for their efficacy.

Lithium – first introduced in 1949 – remains the best established long-term treatment for bipolar disorder, but its benefits are restricted by adverse effects, and alternatives are often needed for long-term treatment.

According to Professor John Geddes, one of the paper's authors, "Combining psychosocial treatments – which can include not just psychotherapy for the patient, but family therapy involving education for their family or caregiver – with mood stabilising drugs might well be one of the most promising lines of treatment for bipolar disorder. However, drug and psychological treatment studies have largely proceeded independently of one another, and research including both would help to move the field forward."

Viewpoint – Working Group members explain new thinking on stress-related mental disorders in ICD-11

WHO is currently developing the International Classification of Diseases, version 11 (ICD-11), a comprehensive, internationally-recognised diagnostic guide for all major diseases, including psychiatric illness. In a Viewpoint published alongside the Series, members of the ICD-11 Working Group on mental disorders associated with stress outline the reasoning behind some of the updates in this area that will appear in the new edition. This includes a substantial tightening of the way in which ICD describes post-traumatic stress disorder (PTSD), a description of normal stress responses that are not considered disorders; the addition of "complex PTSD" to describe extensive reactions arising from severe and prolonged stressors; and inclusion of "prolonged grief disorder", used to describe patients that undergo an intensely painful, disabling, and abnormally persistent response to bereavement.

Comment – DSM-5 criteria for bipolar will "further obfuscate an already confusing diagnostic landscape"

Preparation for an updated version of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has been underway for some years, and the manual is due to appear this month, but in a Comment published alongside the Series, Professor Gin Malhi of the University of Sydney, Australia, expresses concern that the inclusion of a "mixed states specifier" (broadly defined as the coexistence of depressive and manic features) in the criteria for bipolar disorder may lead to diagnostic confusion, and complicate treatment implications. According to Professor Malhi, "the risk is that the diagnostic criterion of mixed states will be used loosely and its application will expand far beyond the most pronounced type of bipolar disorder across the whole bipolar spectrum, without any prognostic significance of therapeutic benefit. The present mix of features in bipolar disorder that will be 'specified' by the new classificatory system will produce a myriad of manifestations and further obfuscate an already confusing diagnostic landscape."

More information: www.thelancet.com/… lar-disorder

Provided by Lancet