Category: Disorders and Syndromes

Symptoms of alcohol abuse, not dependence, may better reflect family risk for alcohol use disorders.

Individuals with alcohol use disorders (AUDs) vary widely in their age of onset of use, patterns of drinking, and symptom profiles. AUDs are often 'divided' into two categories: alcohol abuse (AA) and alcohol dependence (AD), with AA perceived as a milder syndrome that might develop into AD over time. A recent study of the clinical features of AUDs, with a focus on family liability, has found that — contrary to expectations — AA symptoms better reflect familial risk for AUDs than AD symptoms.

Results will be published in the December 2012 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"We decided to look at the clinical features of AA and AD as they correspond to familial liability to AUDs because familial risk of illness has been long used as a major validator of diagnostic approaches in psychiatry," explained Kenneth S. Kendler, professor of psychiatry at the Virginia Commonwealth University School of Medicine and corresponding author for the study. "For example, in the Diagnostic and Statistical Manual of Mental Disorders-III (DSM-III) criteria, it was assumed the AA and AD represent distinct syndromes. Since then, results have accumulated to suggest that these two categories are very highly correlated and may in fact jointly represent one underlying dimension of risk.

The researchers examined clinical features of AUDs among 1,120 twins from the Virginia Twin Study of Psychiatric and Substance Use Disorders who met Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria for lifetime AUDs. Analysis focused on whether clinical features of AUDs, including individual DSM-IV criteria for AD and AA, predicted risk for AUDs in cotwins and/or parents.

Results indicate that individual DSM-IV criteria for AA and AD differ meaningfully in the degree to which they reflect the individual's familial/genetic liability to AUDs. Importantly, and contrary to expectations, the familial/genetic risk to AUDs was better reflected by symptoms of alcohol abuse and negative psychosocial consequences of AUDs than by early age at onset of drinking, or symptoms of tolerance and withdrawal.

"Symptoms of alcohol abuse do a better job of reflecting the familial risk for AUDs than symptoms of dependence," said Kendler. "This is not what we expected. Clearly the symptoms of alcohol abuse may have more validity than they are commonly given credit for."

The most consistent single predictor of familial risk was AUD-associated legal problems, the researchers noted, one of the negative psychosocial consequences of AUDs, which is the one criterion slated for removal in the impending DSM-5.

"This removal is slated to occur largely through the influence of the International Classification of Diseases 11th Revision (ICD-11) which is used worldwide and is itself slated for revision by 2015," explained Kendler. "The DSM-5 authors are concerned that legal standards differ so widely across the world that it would be problematic to use any criteria reflecting legal practices."

 Outdated approaches to preventing and treating substance abuse, barriers to care, and other problems hinder the U.S. Defense Department's ability to curb substance use disorders among military service members and their families, says a new report from the Institute of Medicine. Service members' rising rate of prescription drug addiction and their difficulty in accessing adequate treatment for alcohol and drug-related disorders were among the concerns that prompted members of Congress to request this review.

"We commend the steps that the Department of Defense and individual service branches have recently taken to improve prevention and care for substance use disorders, but the armed forces face many ongoing challenges," said Charles P. O'Brien, Kenneth Appel Professor and vice chair, department of psychiatry, and director, Center for Studies of Addiction, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and chair of the committee that wrote the report. "Better care for service members and their families is hampered by inadequate prevention strategies, staffing shortages, lack of coverage for services that are proved to work, and stigma associated with these disorders. This report recommends solutions to address each of these concerns."

About 20 percent of active duty personnel reported having engaged in heavy drinking in 2008, the latest year for which data are available, and binge drinking increased from 35 percent in 1998 to 47 percent in 2008. While rates of both illicit and prescription drug abuse are low, the rate of medication misuse is rising. Just 2 percent of active duty personnel reported misusing prescription drugs in 2002 compared with 11 percent in 2008. The armed forces' programs and policies have not evolved to effectively address medication misuse and abuse, the committee noted.

To tackle these disorders better, DOD needs to lead from the top to ensure that all service branches take excess drinking and other substance use as seriously as they should, and that they consistently adhere to evidence-based strategies for prevention, screening, and treatment, the report says. Inconsistent use of evidence-based diagnostic and treatment strategies contributes to lower quality care. The department's own Clinical Practice Guideline for Management of Substance Use Disorders is an excellent resource on effective approaches that is not being consistently followed, the committee said.

TRICARE, which provides health insurance to service members and their dependents, does not cover several evidence-based therapies that are now standard practice, the committee found. It also does not permit long-term use of certain medications for the treatment of addiction and covers treatment delivered only in specialized rehabilitation facilities. TRICARE's benefits should be revised to cover maintenance medications and treatment in office-based outpatient settings delivered by a range of providers, which would enable ongoing care for patients struggling to avoid relapses.

Alcohol has long been part of military culture, and attitudes toward drinking vary across the service branches, the committee found. The armed forces should enforce regulations on underage drinking, reduce the number of outlets that sell alcohol on bases, and limit their hours of operation, the report says. In addition, the service branches should conduct routine screening for excessive alcohol consumption in primary care settings and provide brief counseling when screening points to risky behavior. Making screening and intervention services part of primary care would reduce the stigma associated with seeking substance abuse treatment and increase the number of places where service members and families can get basic care for these disorders.

Health care providers should not have to include service members' commanding officers when developing care plans for those who do not meet diagnostic criteria for alcohol use disorders and need only brief counseling. Each branch also should provide options for confidential treatment; the Army's Confidential Alcohol Treatment and Education Pilot offers a promising example.

Military health care professionals at all levels need training in recognizing patterns of substance abuse and misuse and clear guidelines for referring patients to specialists such as pain management experts and mental health providers. Team care by a range of providers not only is a more effective approach but also would help alleviate the provider shortage created by the military's sole reliance on specialty substance abuse clinics to provide care, the committee concluded.

Easier access to providers and better management of substance use disorders could improve detection and care for related conditions, such as post-traumatic stress disorder, depression, and suicidal thoughts, the committee noted. Substance misuse and abuse frequently occur along with these conditions. Rising suicide rates among both active duty personnel and veterans have alarmed the public and government officials.

The report was sponsored by the U.S. Department of Defense. Established in 1970 under the charter of the National Academy of Sciences, the Institute of Medicine provides objective, evidence-based advice to policymakers, health professionals, the private sector, and the public. The Institute of Medicine, National Academy of Sciences, National Academy of Engineering, and National Research Council together make up the independent, nonprofit National Academies. For more information, visit http://national-academies.org or http://iom.edu.

Adequate sleep is an important part of a weight loss plan and should be added to the recommended mix of diet and exercise, states a commentary in CMAJ (Canadian Medical Association Journal).

Although calorie restriction and increased physical activity are recommended for weight loss, there is significant evidence that inadequate sleep is contributing to obesity. Lack of sleep increases the stimulus to consume more food and increases appetite-regulating hormones.

"The solution [to weight loss] is not as simple as 'eat less, move more, sleep more,'" write Drs. Jean-Phillippe Chaput, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario and Angelo Tremblay, Laval University, Québec, Quebec. "However, an accumulating body of evidence suggests that sleeping habits should not be overlooked when prescribing a weight-reduction program to a patient with obesity. Sleep should be included as part of the lifestyle package that traditionally has focused on diet and physical activity."

The authors' recently published research found that total sleep time and quality of sleep predicted the loss of fat in people enrolled in a weight loss program.

The Canadian Obesity Network has included adequate sleep in its new set of obesity management tools for physicians.

Researchers from the Centre for Addiction and Mental Health (CAMH) have identified a new role of a chemical involved in controlling the genes underlying memory and learning.

"The brain is a plastic tissue, and we know that learning and memory require various genes to be expressed," says CAMH Senior Scientist Dr. Art Petronis, who is a senior author on the new study. "Our research has identified how the chemical 5-hmC may be involved in the epigenetic processes allowing this plasticity." Dr. Petronis is head of the Krembil Family Epigenetics Laboratory in CAMH's Campbell Family Mental Health Research Institute.

5-hmC is an epigenetic modification of DNA, and was discovered in humans and mice in 2009. DNA modifications are chemical changes to DNA. They flag genes to be turned "on" — signalling the genome to make a protein — or turned "off." As the overwhelming majority of cells in an individual contain the same genetic code, this pattern of flags is what allows a neuron to use the same genome as a blood or liver cell, but create a completely different and specialized cellular environment.

The research, published online in Nature Structural & Molecular Biology, sheds light on the role of 5-hmC. Intriguingly, it is more abundant in the brain than in other tissues in the body, for reasons not clear to date.

The CAMH team of scientists examined DNA from a variety of tissues, including the mouse and human brain, and looked at where 5-hmC was found in the genome. They detected that 5-hmC had a unique distribution in the brain: it was highly enriched in genes related to the synapse, the dynamic tips of brain cells. Growth and change in the synapse allow different brain cells to "wire" together, which allows learning and memory.

"This enrichment of 5-hmC in synapse-related genes suggests a role for this epigenetic modification in learning and memory," says Dr. Petronis.

The team further showed that 5-hmC had a special distribution even within the gene. The code for one gene can be edited and "spliced" to create several different proteins. Dr. Petronis found that 5-hmC is located at "splice junctions," the points where the gene is cut before splicing.

"5-hmC may signal the cell's splicing machinery to generate the diverse proteins that, in turn, give rise to the unprecedented complexity of the brain," he says.

The research team is continuing to investigate the role of 5-hmC in more detail, and to determine whether 5-hmC function is different in people with bipolar disorder and schizophrenia compared to people without these diagnoses.

This research was funded by the U.S National Institutes of Health, the Canadian Institutes of Health Research, and the Tapscott Chair in Schizophrenia Studies at the University of Toronto.

The Centre for Addiction and Mental Health (CAMH) is Canada's largest mental health and addiction teaching hospital, as well as one of the world's leading research centres in the area of addiction and mental health. CAMH combines clinical care, research, education, policy development and health promotion to help transform the lives of people affected by mental health and addiction issues.

CAMH is fully affiliated with the University of Toronto, and is a Pan American Health Organization/World Health Organization Collaborating Centre.

 Veterans suffering from post-traumatic stress disorder who are also battling drug or alcohol problems face a higher risk of death, according to new research from the University of Michigan Health System and the VA Ann Arbor Healthcare System.

The new study is the first to examine the association between drug or alcohol use disorders and death in veterans with PTSD, and also includes data from the nation's youngest veterans who have returned from conflict in Iraq and Afghanistan.

Kipling Bohnert, Ph.D., the study's lead author, says the research sheds new light on the importance of treating both substance-use and post-traumatic stress disorders in veterans.

"Attention needs to be paid to veteran patients with PTSD, with an emphasis on identifying those who might also have a problem with drug or alcohol use," says Bohnert, who is a post-doctoral fellow at VA Ann Arbor and a research fellow at the University of Michigan. "This study highlights the potential importance of effective treatment for both conditions in helping veterans after they've returned from conflict."

Previous research on veterans has linked PTSD with higher risks of death, but this study is the first to highlight the association between substance-use disorders, PTSD and mortality. The study was published online in the journal Drug and Alcohol Dependence.

While the researchers found a significant link between substance-use disorders and death in veterans with PTSD across all ages, they also found that the association was most pronounced for the youngest group of veterans, including those from conflicts in Iraq and Afghanistan.

The youngest veterans, those 45 and under, showed a particularly strong link between substance-use disorders and both injury and non-injury related death. Injury-related death included homicides, suicides and accidents, while non-injury related deaths included heart disease, cancer and other health problems.

Bohnert says more research is necessary to figure out why younger veterans exhibit a stronger tie between substance-use disorders and death.

Federic C. Blow, Ph.D., the paper's senior author, the director of National Serious Mental Illness Treatment Research & Evaluation Center at the VA, says the research might be helpful for physicians in deciding the best way to treat their patients.

"In theory, a treatment program that addresses both issues — substance use and PTSD — should reduce the risk of death from all causes, and this may be especially true for the nation's youngest veterans," says Blow, who is also the director of the Mental Health Services Outcomes & Translation Section at the U-M Medical School.

The absence of a specific type of neuron in the brain can lead to obesity and diabetes in mice report researchers in The EMBO Journal. The outcome, however, depends on the type of diet that the animals are fed.

A lack of AgRP-neurons, brain cells known to be involved in the control of food intake, leads to obesity if mice are fed a regular carbohydrate diet. However, animals that are deficient in AgRP-neurons but which are raised on a high-fat diet are leaner and healthier. The differences are due to the influence of the AgRP-neurons on the way other tissues in the body break down and store nutrients. Mice lacking AgRP-neurons adapt poorly to a carbohydrate diet and their metabolism seems better suited for feeding on fat.

“Susceptibility to obesity and other metabolic diseases is mostly thought to be due to complex genetic interactions and the radical environmental changes that have occurred during the last century. However, it is not just a question of what you eat and your genetic makeup but also how the body manages to convert, store and use food nutrients,” commented Serge Luquet, lead author of the study and a researcher at the French Centre National de la Recherche Scientifique (CNRS) Unit of Functional and Adaptive Biology, Université Paris Diderot, Sorbonne Paris Cité.

The scientists wanted to show if a primary setting in the brain might directly affect the relative balance that exists in peripheral tissue between storage, conversion and utilization of carbohydrate and lipids. “The idea that we wanted to test in our experiments was whether the action of a specific type of brain cell known as the AgRP-neuron extended beyond its known influence on food intake. We found a new function for these cells, one that affects the communication with and activities of other tissues in the body including the liver, muscle and the pancreas,” added Luquet.

The researchers showed that mice that lacked AgRP-neurons from birth and which were fed on a regular carbohydrate diet had excessive body fat, increased amounts of the sugar-regulating hormone insulin, and normal levels of glucose in the blood. When the same animals were fed a high fat diet they showed a reduced gain in body weight and improved glucose clearance in the blood.

“Our work shows that central circuits in the brain that control food intake also control how nutrients are used in peripheral organs of the body,” remarked Luquet. “This further role for AgRP-neurons might represent a core mechanism linking obesity and obesity-related diseases.”

The prevalence of obesity and other metabolic diseases is increasing rapidly and effective and safe treatments are urgently needed. Obesity adversely affects health, decreases life expectancy, and increases the likelihood of other diseases including heart disease and type II diabetes. “Understanding the mechanisms by which the brain controls how nutrients are metabolized and stored in peripheral organs may prove essential to achieving a clinical breakthrough for these debilitating diseases,” added Luquet.

Journal Reference:

1. Aurélie Joly-Amado, Raphaël G P Denis, Julien Castel, Amélie Lacombe, Céline Cansell, Claude Rouch, Nadim Kassis, Julien Dairou, Patrice D Cani, Renée Ventura-Clapier, Alexandre Prola, Melissa Flamment, Fabienne Foufelle, Christophe Magnan, Serge Luquet. Hypothalamic AgRP-neurons control peripheral substrate utilization and nutrient partitioning. The EMBO Journal, 2012; DOI: 10.1038/emboj.2012.250

Scientists at the Medical College of Wisconsin, in a team led by Carol Everson, Ph.D., professor of neurology, cell biology, neurobiology and anatomy, have discovered abnormalities in bone and bone marrow in rats undergoing chronic lack of sleep. They discovered abnormalities in serum markers of bone metabolism in sleep-deprived rats, which led them to conduct direct measurements of bone parameters; this time in rats experiencing recurrent sleep restriction during a large portion of their young adulthood.

The results show a dramatic imbalance between bone apposition and reabsorption, marked by an arrest in bone formation without reduced absorption. Furthermore, fat in the red marrow is greatly diminished and platelet-generating cells are doubled in number, indicating changes to marrow plasticity. "If the same processes are evoked in humans," said Dr. Everson, "the potential medical implications are far-reaching and may include poor repair of microdamage from activities of daily living, introduction of osteoporotic processes, and changes to progenitor cells that may affect disease predisposition and disease resistance."

The results appear in the September 2012 issue of Experimental Biology and Medicine. Co-authors of the paper are Jeffrey M. Toth, Ph.D., professor of orthopaedic surgery at the Medical College of Wisconsin, and Anne Folley, now a graduate student at George Washington University.

The researchers observed changes in intramembranous ossification and marrow hypercellularity resulting from chronic sleep loss. "Marrow fat was greatly diminished and reflected increased blood cell production and differentiation. Our findings of increased megakaryocyte numbers, for example, suggest that there is an increased demand for cell delivery to the circulation consistent with an inflammatory response, and conceivably the promotion of thrombocytosis," said Dr. Everson.

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said, "With increased life stress due to work-related, financial and other issues a large percentage of us are experiencing difficulties in sleeping. While we know that chronic sleep loss can affect our health little specific information has been available on how it may impact bone formation or loss. Drs. Everson and Toth, together with Anne Folley present exciting results indicating that sleep deprivation in rats arrests new bone formation, decreases fat within the red marrow and increases platelet levels. If true in humans, and I expect that it may be, this work will have great impact on our understanding of the impact of sleep deprivation on osteoporosis and inability to repair bone damage as we age."

Scientists at Charité — Universitätsmedizin Berlin have succeeded in coming closer to determining the risk of relapse in detoxified alcohol-dependent patients. Using an imaging process (magnetic resonance tomography) it was shown that particular regions in the brain demonstrate structural as well as functional abnormalities in relapsed alcohol-dependent patients. Study findings are published in the journal Archives of General Psychiatry.

In the study conducted under the direction of Prof. Andreas Heinz, director of the Charité Department of Psychiatry and Psychotherapy, scientists examined a group of 46 detoxified alcohol-dependent patients, in addition to a large control group. Structural imaging showed anatomical properties of brain substance, and the examination of functional signals in the brain were measured in reaction to alcohol-associated stimuli. After three months, patients were reexamined for eventual relapses; 30 study participants relapsed and 16 continued to be abstinent.

It was proven that relapse patients had increased loss of grey matter in particular regions of the forebrain. This section of the brain is known to be associated primarily with behavioral regulation and emotional control. Furthermore, measurement of functional brain responses in reaction to alcohol-associated stimuli showed that different brain regions were activated in relapsed patients than in patients who remained abstinent. These measurements show that sections of the brain in relapse patients were active that are associated primarily with directing attention to certain stimuli. In contrast, the abstinent patients demonstrated an activation of brain areas that are (among other functions) associated with processing of stimuli inducing aversion (aversive stimuli) or that are particularly important (salient stimuli).

"This characteristic in patients who remained abstinent possibly acts as a warning signal and prevents potential relapse when confronted with alcohol," said Anne Beck, primary author of the study. Future studies could examine these aspects in greater depth and take eventual factors of alcohol dependency into consideration, like for example, genetic mechanisms. Thus people with a particularly high risk of relapse could be identified and systematically supported with therapy.

Contrary to the prevailing theories that music and language are cognitively separate or that music is a byproduct of language, theorists at Rice University's Shepherd School of Music and the University of Maryland, College Park (UMCP) advocate that music underlies the ability to acquire language.

"Spoken language is a special type of music," said Anthony Brandt, co-author of a theory paper published online this month in the journal Frontiers in Cognitive Auditory Neuroscience. "Language is typically viewed as fundamental to human intelligence, and music is often treated as being dependent on or derived from language. But from a developmental perspective, we argue that music comes first and language arises from music."

Brandt, associate professor of composition and theory at the Shepherd School, co-authored the paper with Shepherd School graduate student Molly Gebrian and L. Robert Slevc, UMCP assistant professor of psychology and director of the Language and Music Cognition Lab.

"Infants listen first to sounds of language and only later to its meaning," Brandt said. He noted that newborns' extensive abilities in different aspects of speech perception depend on the discrimination of the sounds of language — "the most musical aspects of speech."

The paper cites various studies that show what the newborn brain is capable of, such as the ability to distinguish the phonemes, or basic distinctive units of speech sound, and such attributes as pitch, rhythm and timbre.

The authors define music as "creative play with sound." They said the term "music" implies an attention to the acoustic features of sound irrespective of any referential function. As adults, people focus primarily on the meaning of speech. But babies begin by hearing language as "an intentional and often repetitive vocal performance," Brandt said. "They listen to it not only for its emotional content but also for its rhythmic and phonemic patterns and consistencies. The meaning of words comes later."

Brandt and his co-authors challenge the prevailing view that music cognition matures more slowly than language cognition and is more difficult. "We show that music and language develop along similar time lines," he said.

Infants initially don't distinguish well between their native language and all the languages of the world, Brandt said. Throughout the first year of life, they gradually hone in on their native language. Similarly, infants initially don't distinguish well between their native musical traditions and those of other cultures; they start to hone in on their own musical culture at the same time that they hone in on their native language, he said.

The paper explores many connections between listening to speech and music. For example, recognizing the sound of different consonants requires rapid processing in the temporal lobe of the brain. Similarly, recognizing the timbre of different instruments requires temporal processing at the same speed — a feature of musical hearing that has often been overlooked, Brandt said.

"You can't distinguish between a piano and a trumpet if you can't process what you're hearing at the same speed that you listen for the difference between 'ba' and 'da,'" he said. "In this and many other ways, listening to music and speech overlap." The authors argue that from a musical perspective, speech is a concert of phonemes and syllables.

"While music and language may be cognitively and neurally distinct in adults, we suggest that language is simply a subset of music from a child's view," Brandt said. "We conclude that music merits a central place in our understanding of human development."

Brandt said more research on this topic might lead to a better understanding of why music therapy is helpful for people with reading and speech disorders. People with dyslexia often have problems with the performance of musical rhythm. "A lot of people with language deficits also have musical deficits," Brandt said.

More research could also shed light on rehabilitation for people who have suffered a stroke. "Music helps them reacquire language, because that may be how they acquired language in the first place," Brandt said.

The research was supported by Rice's Office of the Vice Provost for Interdisciplinary Initiatives, the Ken Kennedy Institute for Information Technology and the Shepherd School of Music.

— Levels of sleep problems in the developing world are approaching those seen in developed nations, linked to an increase in problems like depression and anxiety.