Memantine May Improve Cognition in Bipolar Disorder

A drug that for years has been approved to treat moderate to severe Alzheimer’s disease may have a role in improving the cognitive deficits associated with bipolar disorder.

In a randomized, controlled, parallel-arm clinical trial of adjuvant memantine vs placebo in euthymic patients with bipolar disorder, memantine improved several cognitive domains and also demonstrated increased hippocampus neuronal viability on imaging scans of the brain.

The trial was presented in a rapid communication session here at the 10th International Conference on Bipolar Disorders (ICBD).

“Subjects with bipolar disorder have significant cognitive and functional deficits, even when they are euthymic,” lead author Dan Iosifescu, MD, director, Mood and Anxiety Disorders Program, Icahn School of Medicine at Mount Sinai, New York City, told Medscape Medical News.

“This is something that is not usually recognized, and it is important because it has a direct impact on the individual’s ability to function in real life, even when their symptoms of depression are somewhat controlled,” Dr. Iosifescu said.

Problems with attention, short-term memory, and executive functioning exist, but there is little understanding about what will be helpful to improve or compensate for such deficits, he added.

“For a very long time, these cognitive deficits were interpreted as having some residual symptoms, depression or mania, and that these needed to be better controlled, perhaps with increased doses of mood stabilizers. But as it turns out, this is not the right answer, and a lot of people continue to have cognitive problems,” he said.

by Fran Lowry, Medscape

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Stress-Induced Bipolar Disorder Linked to Genetic Abnormality

People with certain genetic profiles may have an increased risk of developing bipolar disorder after experiencing stressful life events such as death of a loved one, divorce, or job loss, according to new research.

“It seems to be that your genetic makeup in the presence of stress may increase your susceptibility for developing bipolar disorder,” lead author Georgina Hosang, PhD, from the Institute of Psychiatry, King’s College London and Middlesex University, in London, United Kingdom, told Medscape Medical News.

“If this finding is replicated, perhaps we can identify individuals who are more sensitive to their environment and target them in terms of equipping them with skills to better manage stress,” Dr. Hosang said here at the 10th International Conference on Bipolar Disorders (ICBD).

by Fran Lowry, Medscape

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Photo From “Developing Developers” Training


ESCH Developing Developer Class
ESCH Developing Developer Class

ESCH “Developing Developers” – Linda Stalters, SARDAA Founder and Executive Director, took the ESCH classes to learn how SARDAA can grow through fund development.

“My mentors, Ron Swofford and Jay Taylor, have been invaluable in guiding and directing me and helping the SARDAA Board progress and increase our sustainability.”

First Major Study of Suicide Motivations to Advance Prevention

A University of British Columbia study sheds important new light on why people attempt suicide and provides the first scientifically tested measure for evaluating the motivations for suicide.

Published in the official journal of the American Association of Suicidology, the work gives doctors and researchers important new resources to advance suicide prevention, improve treatments, and reduce the likelihood of further attempts.

“Knowing why someone attempted suicide is crucial – it tells us how to best help them recover,” says Prof. David Klonsky, UBC Dept. of Psychology. “This new tool will help us to move beyond the current “one-size-fits-all” approach to suicide prevention, which is essential. Different motivations require different treatments and interventions.”

The study, based on 120 participants who recently attempted suicide, suggests many motivations believed to play important roles in suicide are relatively uncommon. For example, suicide attempts were rarely the result of impulsivity, a cry for help, or an effort to solve a financial or practical problem. Of all motivations for suicide, the two found to be universal in all participants were hopelessness and overwhelming emotional pain.


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Effectiveness of Long-term Use of Antipsychotic Medication to Treat Childhood Schizophrenia is Limited

Few youths with early-onset schizophrenia who are treated with antipsychotic medications for up to a year appear to benefit from their initial treatment choice over the long term, according to results from an NIMH-funded study. The study was published online ahead of print May 4, 2010, in the Journal of the American Academy of Child and Adolescent Psychiatry.


The NIMH Treatment of Early Onset Schizophrenia Study (TEOSS) included 116 youth between 8 and 19 years old, diagnosed with early onset schizophrenia spectrum disorder (EOSS). The TEOSS team randomly assigned the children to eight weeks of either olanzapine (Zyprexa) or risperidone (Risperdal)—both new generation atypical antipsychotics—or to the older conventional antipsychotic molindone (Moban). Response rates after eight weeks of treatment were comparable among the three medications. The results were reported in September 2008.

After the initial 8-week trial, 54 of the 116 participants entered the maintenance treatment phase in which they continued their initial medication and were monitored for up to 44 more weeks of treatment. Only 14 participants completed the additional 44 weeks of treatment.

Results of the Study

Robert Findling, M.D., of Case Western Reserve University in Cleveland, and the TEOSS team reported that the participants’ treatment response tended to plateau during the follow-up, maintenance therapy period, such that most of the children did not improve beyond what they had already achieved during the initial eight weeks of treatment. In addition, most discontinued treatment during the maintenance phase, most commonly due to side effects such as weight gain, anxiety, increases in cholesterol levels, and other metabolic changes, regardless of which treatment they were receiving. None of the three medications appeared to be more effective than the others.


The findings suggest that few youths with EOSS continue treatment on the same antipsychotic medication over the long-term, with lack of effectiveness and adverse effects cited as the most common reasons for discontinuation. Most of those who initially responded to medication were able to at least maintain their initial improvements, but very few participants stayed on the medication through the 12-month study most frequently because of intolerable side effects.

What’s Next

The authors conclude that more effective and safer treatments need to be developed to treat children with EOSS.

–National Institute of Mental Health (NIMH)

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Volunteering Reduces Risk of Hypertension in Older Adults


It turns out that helping others can also help you protect yourself from high blood pressure.

New research from Carnegie Mellon University shows that older adults who volunteer for at least 200 hours per year decrease their risk of hypertension, or high blood pressure, by 40 percent. The study, published by the American Psychological Association’s Psychology and Aging journal, suggests that volunteer work may be an effective non-pharmaceutical option to help prevent the condition. Hypertension affects an estimated 65 million Americans and is a major contributor to cardiovascular disease, the leading cause of death in the U.S.

“Everyday, we are learning more about how negative lifestyle factors like poor diet and lack of exercise increase hypertension risk,” said Rodlescia S. Sneed, a Ph.D. candidate in psychology in CMU’s Dietrich College of Humanities and Social Sciences and lead author of the study. “Here, we wanted to determine if a positive lifestyle factor like volunteer work could actually reduce disease risk. And, the results give older adults an example of something that they can actively do to remain healthy and age successfully.”


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Rare Gene Glitch May Hold Clues for Schizophrenia

A North Star Amid “A Constellation of Multiple Rare Diseases”

Scientists are eyeing a rare genetic glitch for clues to improved treatments for some people with schizophrenia — even though they found the mutation in only one third of 1 percent of patients.

In the study, funded in part by the National Institutes of Health, schizophrenia patients were 14 times more likely than controls to harbor multiple copies of a gene on Chromosome 7. The mutations were in the gene for VIPR2, the receptor for vasoactive intestinal peptide (VIP) — a chemical messenger known to play a role in brain development. An examination of patients’ blood confirmed that they had overactive VIP activity.

Discovery of the same genetic abnormality in even a small group of patients buoys hopes for progress in a field humbled by daunting complexity in recent years. The researchers’ previous studies had suggested that the brain disorder that affects about 1 percent of adults might, in many cases, be rooted in different genetic causes in each affected individual, complicating prospects for cures.

“Genetic testing for duplications of the VIP receptor could enable early detection of a subtype of patients with schizophrenia, and the receptor could also potentially become a target for development of new treatments,” explained Jonathan Sebat, Ph.D., of the University of California, San Diego, who led the research team. “The growing number of such rare duplications and deletions found in schizophrenia suggests that what we have been calling a single disorder may turn out, in part, to be a constellation of multiple rare diseases.”

Sebat, a grantee of the NIH’s National Institute of Mental Health — and colleagues at 14 research centers world-wide – report on their findings Feb. 23, 2011, in the journal Nature.

“Although such copy number variations may explain only a small fraction of cases, these rare mutations can yield important clues to the underlying causes of more common forms,” noted NIMH Director Thomas R. Insel, M.D. “This new finding with VIPR2 suggests a series of important follow up studies, even in people without the mutation.”

Schizophrenia is known to have a strong genetic component –– having a parent or sibling with the disorder increases one’s risk tenfold. Yet, genetic studies have so far explained relatively few cases of the illness. As hopes wane that common genetic variations might account for many cases, evidence is mounting that patients harbor disproportionately large numbers of individually rare copy number variations (CNVs) — some shared in families, but many apparently unique to one individual.

The VIPR2 CNV is among the first to implicate a specific gene and neurobiological pathway in schizophrenia. CNVs previously identified, spanning dozens of genes, were too large to yield such clues. In the new genome-wide scan, Sebat and colleagues found the mutation in 29 of 8290 patients (.35 percent) compared to only 2 of 7431 healthy controls. A few other schizophrenia-linked CNVs seen in previous studies were also detected.

VIP and its receptor are known to play a role in regulating the growth of neurons and in learning and memory. They are also expressed in the immune and cardiovascular systems and in the gut – hence its name.

When VIP binds to the VIPR2 receptor on a neuron, it triggers a key relay chemical within the cell, called cyclic AMP. The researchers found that both VIP and cyclic AMP were overactive in blood cells of patients with the VIPR2 mutations.

“It’s likely that cyclic AMP signaling is disturbed in a larger fraction of patients, so it’s possible that a treatment that targets VIPR2 might have benefits even for people who don’t have mutations in the VIPR2 gene,” said Sebat. “It looks like the volume is turned-up in the whole VIP signaling pathway.”

Since the mutations lead to an overexpression of VIPR2, agents that block the receptor, which already exist, might hold potential for treatment development, he added.

In addition to genetic screening of patients for such personalized medicine, Sebat sees opportunities in the new findings for neuroimaging studies. “We must determine how over-expression of VIPR2 impacts the growth, differentiation and function of neurons – and how that influence behavior. Knowing where the VIPR2 gene is expressed in the human brain can point us to specific regions where VIP activity levels may differ between people who carry this mutation and those who don’t.”

Despite the challenges posed by the complexities of CNVs, Sebat is upbeat about prospects for ultimately making sense of the emerging evidence about schizophrenia genetics.

“We hypothesize that the many different genetic causes of schizophrenia may have something in common,” he said. “There may be larger groups of patients who may not share the same mutation but, may share the same underlying neurobiological defect.”

 –National Institute of Mental Health (NIMH)

Weight Loss Improves Memory and Alters Brain Activity in Overweight Women

Memory improves in older, overweight women after they lose weight by dieting, and their brain activity actually changes in the regions of the brain that are important for memory tasks, a new study finds. The results were presented today at The Endocrine Society’s 95th Annual Meeting in San Francisco.

“Our findings suggest that obesity-associated impairments in memory function are reversible, adding incentive for weight loss,” said lead author Andreas Pettersson, MD, a PhD student at Umea University, Umea, Sweden.

Previous research has shown that obese people have impaired episodic memory, the memory of events that happen throughout one’s life.

Pettersson and co-workers performed their study to determine whether weight loss would improve memory and whether improved memory correlated with changes in relevant brain activity. A special type of brain imaging called functional magnetic resonance imaging (functional MRI) allowed them to see brain activity while the subjects performed a memory test.


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‘Cuddle Hormone’ Could Help Depression Sufferers to Seek Support

Scientists believe that treating those in distress with oxytocin, a hormone linked to emotional bonding in childbirth and breastfeeding, could help to stop them withdrawing from the help of their friends and family.

New research has shown that the hormone can increase people’s trust in others following social rejection.

….Dr Mark Ellenbogen, from Concordia University in Montreal, Canada, who carried out the study, said: “That means that instead of the traditional ‘fight or flight’ response to social conflict, where people get revved up to respond to a challenge or run away from it, oxytocin may promote the ‘tend and befriend’ response, where people reach out to others for support after a stressful event.

“That can, in turn, strengthen social bonds and may be a healthier way to cope.”

People with depression might benefit in particular from being given oxytocin because they naturally tend to withdraw even though seeking help can aid their recovery.

by Sam Marsden, The Telegraph

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The Suicide Detective

For reasons that have eluded people forever, many of us seem bent on our own destruction. Recently more human beings have been dying by suicide annually than by murder and warfare combined. Despite the progress made by science, medicine and mental-health care in the 20th century — the sequencing of our genome, the advent of antidepressants, the reconsidering of asylums and lobotomies — nothing has been able to drive down the suicide rate in the general population.

….I listened to Nock and his researchers discuss a study they were collaborating on with the Army. They were calling soldiers who had recently attempted suicide and asking them to explain what they had done and why. Nock hoped that sifting through the interview transcripts for repeated phrasings or themes might suggest predictive patterns that he could design tests to catch. A clinical psychologist, he had trained each of his researchers how to ask specific questions over the telephone. Adam Jaroszewski, an earnest 29-year-old in tortoiseshell glasses, told me that he had been nervous about calling subjects in the hospital, where they were still recovering, and probing them about why they tried to end their lives: Why that moment? Why that method? Could anything have happened to make them change their minds? Though the soldiers had volunteered to talk, Jaroszewski worried about the inflections of his voice: how could he put them at ease and sound caring and grateful for their participation without ceding his neutral scientific tone? Nock, he said, told him that what helped him find a balance between empathy and objectivity was picturing Columbo, the frumpy, polite, persistently quizzical TV detective played by Peter Falk. “Just try to be really, really curious,” Nock said.

That curiosity has made Nock, 39, one of the most original and influential suicide researchers in the world. In 2011, he received a MacArthur genius award for inventing new ways to investigate the hidden workings of a behavior that seems as impossible to untangle, empirically, as love or dreams.

by Kim Tingley, The New York Times

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