Posts tagged depression
Articles and news from the latest research reports.
Depressed Stroke Survivors May Face Triple the Risk of Death
People who are depressed after a stroke may have a tripled risk of dying early and four times the risk of death from stroke than people who have not experienced a stroke or depression, according to a study released today that will be presented at the American Academy of Neurology’s 65th Annual Meeting in San Diego, March 16 to 23, 2013. “Up to one in three people who have a stroke develop depression,” said study author Amytis Towfighi, MD, with the Keck School of Medicine of the University of Southern California and Rancho Los Amigos National Rehabilitation Center in Los Angeles, and a member of the American Academy of Neurology. “This is something family members can help watch for that could potentially save their loved one.”
Towfighi noted that similar associations have been found regarding depression and heart attack, but less is known about the association between stroke, depression and death.
The research included 10,550 people between the ages of 25 and 74 followed for 21 years. Of those, 73 had a stroke but did not develop depression, 48 had stroke and depression, 8,138 did not have a stroke or depression and 2,291 did not have a stroke but had depression.
After considering factors such as age, gender, race, education, income level and marital status, the risk of dying from any cause was three times higher in individuals who had stroke and depression compared to those who had not had a stroke and were not depressed. The risk of dying from stroke was four times higher among those who had a stroke and were depressed compared to people who had not had a stroke and were not depressed.
“Our research highlights the importance of screening for and treating depression in people who have experienced a stroke,” said Towfighi. “Given how common depression is after stroke, and the potential consequences of having depression, looking for signs and symptoms and addressing them may be key.”
Declining Access to Electroconvulsive Therapy: A Clinical Choice or an Economic One?
Horrific images from One Flew Over the Cuckoo’s Nest notwithstanding, modern electroconvulsive therapy (ECT) remains one of the safest and most effective antidepressant treatments, particularly for patients who do not tolerate antidepressant medications or depression symptoms that have failed to respond to antidepressant medications.
Since its introduction in the 1930s, ECT has evolved into a more refined, but more expensive and extensively regulated clinical procedure. Each treatment involves the assembly of a multidisciplinary clinical team and the use of a highly specialized device to deliver brief pulses of low dose electric currents to the brain. ECT is performed while the patient is under general anesthesia and, depending upon each individual’s response, is usually administered 2-3 times a week for 6-12 sessions.
A new study in Biological Psychiatry suggests that reductions in ECT treatment have an economic basis. From 1993 - 2009, there was a progressive decline in the number of hospitals offering ECT treatment, resulting in an approximately 43% drop in the number of psychiatric inpatients receiving ECT.
Using diagnostic and discharge codes from survey data compiled annually from US hospitals, researchers calculated the annual number of inpatient stays involving ECT and the annual number of hospitals performing the procedure.
Lead author Dr. Brady Case, from Bradley Hospital and Brown University, said, “Our findings document a clear decline in the capacity of US general hospitals - which provide the majority of inpatient mental health care in this country - to deliver an important treatment for some of their most seriously ill patients. Most Americans admitted to general hospitals for severe recurrent major depression are now being treated in facilities which do not conduct ECT.”
This is the consequence of an approximately 15 year trend in which psychiatric units appear to be discontinuing use of the procedure. The percentage of hospitals with psychiatric units which conduct ECT dropped from about 55% in 1993 to 35% in 2009, which has led to large reductions in the number of inpatients receiving ECT.
Analyses of treatment for inpatients with severe, recurrent depression indicate the changes have equally affected inpatients with indications like psychotic depression and with relative medical contraindications, suggesting declines have been clinically indiscriminate. By contrast, non-clinical patient factors like residence in a poor neighborhood and lack of private insurance have remained important predictors of whether patients’ treating hospitals conduct ECT, raising the concern of systemic barriers to ECT for the disadvantaged.
Where hospitals have continued to conduct the procedure, use has remained stable, indicating divergence in the care of patients treated in the large academic facilities most likely to conduct ECT and those treated elsewhere.
"Psychiatry has taken a step backward. The suffering and disability associated with antidepressant-resistant depression constitute a profound burden on the patient, their family, and society. ECT remains the gold standard treatment for treatment-resistant depression," commented Dr. John Krystal, Editor of Biological Psychiatry. "We must insure that patients with the greatest need for definitive treatment have access to this type of care. ECT may be one of the oldest treatments for depression, but its role in treatment has been given new life in light of a generation of research that has outlined molecular signatures of ECT’s antidepressant efficacy."
(Source: alphagalileo.org)
Dopamine regulates the motivation to act
The widespread belief that dopamine regulates pleasure could go down in history with the latest research results on the role of this neurotransmitter. Researchers have proved that it regulates motivation, causing individuals to initiate and persevere to obtain something either positive or negative.
The neuroscience journal Neuron publishes an article by researchers at the Universitat Jaume I of Castellón that reviews the prevailing theory on dopamine and poses a major paradigm shift with applications in diseases related to lack of motivation and mental fatigue and depression, Parkinson’s, multiple sclerosis, fibromyalgia, etc. and diseases where there is excessive motivation and persistence as in the case of addictions.
"It was believed that dopamine regulated pleasure and reward and that we release it when we obtain something that satisfies us, but in fact the latest scientific evidence shows that this neurotransmitter acts before that, it actually encourages us to act. In other words, dopamine is released in order to achieve something good or to avoid something evil", explains Mercè Correa.
Studies had shown that dopamine is released by pleasurable sensations but also by stress, pain or loss. These research results however had been skewed to only highlight the positive influence, according to Correa. The new article is a review of the paradigm based on the data from several investigations, including those conducted over the past two decades by the Castellón group in collaboration with the John Salamone of the University of Connecticut (USA), on the role of dopamine in the motivated behaviour in animals.
The level of dopamine depends on individuals, so some people are more persistent than others to achieve a goal. “Dopamine leads to maintain the level of activity to achieve what is intended. This in principle is positive, however, it will always depend on the stimuli that are sought: whether the goal is to be a good student or to abuse of drugs” says Correa. High levels of dopamine could also explain the behaviour of the so-called sensation seekers as they are more motivated to act.
Application for depression and addiction
To know the neurobiological parameters that make people be motivated by something is important to many areas such as work, education or health. Dopamine is now seen as a core neurotransmitter to address symptoms such as the lack of energy that occurs in diseases such as depression. “Depressed people do not feel like doing anything and that’s because of low dopamine levels,” explains Correa. Lack of energy and motivation is also related to other syndromes with mental fatigue such as Parkinson’s, multiple sclerosis or fibromyalgia, among others.
In the opposite case, dopamine may be involved in addictive behaviour problems, leading to an attitude of compulsive perseverance. In this sense, Correa indicates that dopamine antagonists which have been applied so far in addiction problems probably have not worked because of inadequate treatments based on a misunderstanding of the function of dopamine.
Late-Life Depression Associated with Prevalent Mild Cognitive Impairment, Increased Risk of Dementia
Depression in a group of Medicare recipients ages 65 years and older appears to be associated with prevalent mild cognitive impairment and an increased risk of dementia, according to a report published Online First by Archives of Neurology, a JAMA Network publication.
Depressive symptoms occur in 3 percent to 63 percent of patients with mild cognitive impairment (MCI) and some studies have shown an increased dementia risk in individuals with a history of depression. The mechanisms behind the association between depression and cognitive decline have not been made clear and different mechanisms have been proposed, according to the study background.
Edo Richard, M.D., Ph.D., of the University of Amsterdam, the Netherlands, and colleagues evaluated the association of late-life depression with MCI and dementia in a group of 2,160 community-dwelling Medicare recipients.
“We found that depression was related to a higher risk of prevalent MCI and dementia, incident dementia, and progression from prevalent MCI to dementia, but not to incident MCI,” the authors note.
Baseline depression was associated with prevalent MCI (odds ratio [OR], 1.4) and dementia (OR, 2.2), while baseline depression was associated with an increased risk of incident dementia (hazard ratio [HR], 1.7) but not with incident MCI (HR, 0.9). Patients with MCI and coexisting depression at baseline also had a higher risk of progression to dementia (HR, 2.0), especially vascular dementia (HR, 4.3), but not Alzheimer disease (HR, 1.9), according to the study results.
“Our finding that depression was associated cross sectionally with both MCI and dementia and longitudinally only with dementia suggests that depression develops with the transition from normal cognition to dementia,” the authors conclude.
(Source: media.jamanetwork.com)
Brain & Behavior Research Foundation Announces 10 Major Research Achievements of 2012
In 2012, the Brain & Behavior Research Foundation funded more than 200 new promising ideas through its NARSAD Grants to identify the causes, improve treatments and develop prevention strategies for mental illness. Many research projects also came to fruition in 2012, and the Foundation highlights ten significant findings.
Stress-Resilience/Susceptibility Traced to Neurons in Reward Circuit
A specific pattern of neuronal firing in a brain reward circuit instantly rendered mice vulnerable to depression-like behavior induced by acute severe stress, a study supported by the National Institutes of Health has found. When researchers used a high-tech method to mimic the pattern, previously resilient mice instantly succumbed to a depression-like syndrome of social withdrawal and reduced pleasure-seeking – they avoided other animals and lost their sweet tooth. When the firing pattern was inhibited in vulnerable mice, they instantly became resilient.
“For the first time, we have shown that split-second control of specific brain circuitry can switch depression-related behavior on and off with flashes of an LED light,” explained Ming-Hu Han, Ph.D., of the Mount Sinai School of Medicine, New York City, a grantee of NIH’s National Institute of Mental Health (NIMH). “These results add to mounting clues about the mechanism of fast-acting antidepressant responses.” Han, Eric Nestler, M.D., Ph.D., of Mount Sinai, and colleagues, report on their study online, Dec. 12, 2012, in the journal Nature.
In a companion article, NIMH grantees Kay Tye, Ph.D., of the Massachusetts Institute of Technology, Cambridge, Mass., and Karl Deisseroth, M.D., Ph.D., of Stanford University, Stanford, Calif., used the same cutting-edge technique to control mouse brain activity in real time. Their study reveals that the same reward circuit neuronal activity pattern had the opposite effect when the depression-like behavior was induced by daily presentations of chronic, unpredictable mild physical stressors, instead of by shorter-term exposure to severe social stress.
Prior to the new studies, Han’s team suspected that a telltale pattern – rapid firing of neurons that secrete the chemical messenger dopamine in a key circuit hub – makes an animal vulnerable to the depression-like effects of acute severe stress, and that slower firing supports resilience. But they lacked direct, real-time evidence.
To pinpoint cause-and-effect, they turned to a research technology pioneered by Deisseroth, called optogenetics. It melds fiber optics and genetic engineering to precisely control the activity of a specific brain circuit in a living, behaving animal. Genetically modified viruses are used to inject light-reactive proteins, borrowed from primitive organisms like algae, to make the circuitry similarly light-responsive.
Researchers at Stanford University have successfully induced and relieved depression-like deficiencies in both pleasure and motivation in mice by controlling just a single area of the brain known as the ventral tegmental area. It is the first time that well-defined types of neurons within a specific brain region have been directly tied to the control of myriad symptoms of major depressive illness.
In the paper published in Nature on Dec. 12, Stanford bioengineer Karl Deisseroth, MD, PhD, and a team including postdoctoral scholars Kay Tye, PhD, and Melissa Warden, PhD, and research assistant Julie Mirzabekov have used a technique known as optogenetics to pinpoint a specific brain location that produces multiple depression-like symptoms. The region in question is the ventral tegmental area, or VTA, a source of dopamine and a central player in the brain’s internal motivation and reward systems.
“We have for the first time directly tied dopamine neurons in the VTA to controlling and relieving these very different and diverse symptoms,” said Deisseroth, the study’s senior author and a professor of bioengineering and of psychiatry and behavioral sciences. “While depression is a complex disease with still many unknowns, this knowledge may help launch new kinds of investigation into the pathways of depression in the brain, and develop concepts to help people suffering from depression.”
Deisseroth’s team was able to both induce and relieve multiple depression-like symptoms in laboratory mice by genetically modifying the dopamine neurons in the VTA to be sensitive to light. Using fiber optic cables inserted in rodents’ brains, they could then instantaneously produce and inhibit the depression-like symptoms by turning the light on and off. This research technique, developed by Deisseroth at Stanford in 2005, is known as optogenetics.
(Image Credit: iStockphoto.com)
Experimental Agent Briefly Eases Depression Rapidly in Test
A drug that works through the same brain mechanism as the fast-acting antidepressant ketamine briefly improved treatment-resistant patients’ depression symptoms in minutes, with minimal untoward side effects, in a clinical trial conducted by the National Institutes of Health. The experimental agent, called AZD6765, acts through the brain’s glutamate chemical messenger system.
Existing antidepressants available through prescription, which work through the brain’s serotonin system, take a few weeks to work, imperiling severely depressed patients, who can be at high risk for suicide. Ketamine also works in hours, but its usefulness is limited by its potential for dissociative side-effects, including hallucinations. It is being studied mostly for clues to how it works.
“Our findings serve as a proof of concept that we can tap into an important component of the glutamate pathway to develop a new generation of safe, rapid-acting practical treatments for depression,” said Carlos Zarate, M.D., of the NIH’s National Institute of Mental Health, which conducted the research.
Zarate, and colleagues, reported on their results online Dec. 1, 2012 in the journal Biological Psychiatry.
AZD6765, like ketamine, works by blocking glutamate binding to a protein on the surface of neurons, called the NMDA receptor. It is a less powerful blocker of the NMDA receptor, which may be a reason why it is better tolerated than ketamine.
About 32 percent of 22 treatment-resistant depressed patients infused with ASD6765 showed a clinically meaningful antidepressant response at 80 minutes after infusion that lasted for about half an hour – with residual antidepressant effects lasting two days for some. By contrast, 52 percent of patients receiving ketamine show a comparable response, with effects still detectable at seven days. So a single infusion of ketamine produces more robust and sustained improvement, but most patients continue to experience some symptoms with both drugs.
However, depression rating scores were significantly better among patients who received AZD6765 than in those who received placebos. The researchers deemed this noteworthy, since, on average, these patients had failed to improve in seven past antidepressant trials, and nearly half failed to respond to electroconvulsive therapy (ECT).
The patients reported only minor side effects, such as dizziness and nausea, which were not significantly different from those experienced with the placebo.
Zarate and colleagues say their results warrant further trials with AZD6765, testing whether repeated infusions a few times per week or higher doses might produce longer-lasting results.
(Source: nimh.nih.gov)
Discovery of pathway leading to depression reveals new drug targets
Scientists have identified the key molecular pathway leading to depression, revealing potential new targets for drug discovery, according to research led by King’s College London’s Institute of Psychiatry. The study, published in Neuropsychopharmacology, reveals for the first time that the ‘Hedgehog pathway’ regulates how stress hormones, usually elevated during depression, reduce the number of brain cells.
Depression affects approximately 1 in 5 people in the UK at some point in their lives. The severity of symptoms can range from feelings of sadness and hopelessness to, in the most severe cases, self-harm or suicide. Treatment for depression involves either medication or talking treatment, or usually a combination of the two.
Recent studies have demonstrated that depression is associated with a reduction in a brain process called ‘neurogenesis’- the ability of the brain to produce new brain cells. However, the pathway responsible for this process has, until now, remained unknown.
In this study, Dr Christoph Anacker from the Centre for the Cellular Basis of Behaviour (CCBB) at King’s Institute of Psychiatry and his team studied human stem cells, which are the source of new cells in the human brain, to investigate the effect of stress hormones on brain cell development. The study was funded by the National Institute for Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and King’s College London and the Medical Research Council UK.
Stress hormones, such as cortisol, are generally elevated in stress and depression. The team studied stem cells in a laboratory and found that high concentrations of cortisol damaged these stem cells and reduced the number of newborn brain cells. They discovered that a specific signalling mechanism in the cell, the ‘Hedgehog pathway’, is responsible for this process. Then, using an animal model, the team confirmed that exposure to stress inhibited this pathway in the brain.
Finally, in order to test the findings, the researchers used a compound called purmorphamine, which is known to stimulate the Hedgehog pathway. They found that by using this drug, they were able to reverse the damaging effects of stress hormones, and normalise the production of new brain cells.
Scientists identify depression and anxiety biomarker in youths
Scientists have discovered a cognitive biomarker – a biological indicator of a disease – for young adolescents who are at high risk of developing depression and anxiety. Their findings were published in the journal PLOS ONE.
The test for the unique cognitive biomarker, which can be done on a computer, could be used as an inexpensive tool to screen adolescents for common emotional mental illnesses. As the cognitive biomarker may appear prior to the symptoms of depression and anxiety, early intervention (which has proven to be one of the most effective ways of combatting mental illness) could then be initiated.
For the study, 15-18 year old participants underwent genetic testing and environmental assessment, an exercise which would currently be too expensive and take too long to use as a widespread method of screening. The adolescents were then given a computer test to gauge how they process emotional information. The test had the participants evaluate whether words were positive, negative or neutral (examples included ‘joyful’ for positive, ‘failure’ for negative, and ‘range’ for neutral).
Those adolescents with a variation of one gene (the short form of the serotonin transporter) as well as exposure to intermittent family arguments for longer than six months and violence between parents before the age of six were shown to have marked difficulty in evaluating the emotion within the words, indicating an inability to process emotional information. Previous research associated a maladjusted perception and response to emotions, as seen here, with a significantly increased risk of depression and anxiety.
Professor Ian Goodyer, Principal Investigator on the study from the University of Cambridge, said: “Whether we succumb to anxiety and depression depends in part on our tendencies to think well or poorly of ourselves at troubled times. How it comes about that some people see the ‘glass half full’ and think positively whereas other see the ‘glass half empty’ and think negatively about themselves at times of stress is not known.
The evidence is that both our genes and our early childhood experiences contribute to such personal thinking styles. Before there are any clinical symptoms of depression or anxiety, this test reveals a deficient ability to efficiently and effectively perceive emotion processes in some teenagers – a biomarker for low resilience which may lead to mental illnesses.”