Posts tagged depression

April 4, 2012

Brain pacemakers have a long-term effect in patients with the most severe depression. This has now been proven by scientists from the Bonn University Medical Center. Eleven patients took part in the study over a period of two to five years. A lasting reduction in symptoms of more than 50 percent was seen in nearly half of the subjects. The results are now being presented in the current edition of the journal Neuropsychopharmacology.

People with severe depression are constantly despondent, lacking in drive, withdrawn and no longer feel joy. Most suffer from anxiety and the desire to take their own life. Approximately one out of every five people in Germany suffers from depression in the course of his/her life – sometimes resulting in suicide. People with depression are frequently treated with psychotherapy and medication. “However, many patients are not helped by any therapy,” says Prof. Dr. Thomas E. Schläpfer from the Bonn University Medical Center for Psychiatry and Psychotherapy. “Many spend more than ten years in bed – not because they are tired, but because they have no drive at all and they are unable to get up.”

One possible alternative is “deep brain stimulation,” in which electrodes are implanted in the patient’s brain. The target point is the nucleus accumbens - an area of the brain known as the gratification center. There, a weak electrical current stimulates the nerve cells. Brain pacemakers of this type are often used today by neurosurgeons and neurologists to treat ongoing muscle tremors in Parkinson’s disease.

A 2009 study proved an antidepressive effect

In 2009, the Bonn scientists were able to establish that brain pacemakers also demonstrate an effect in the most severely depressed patients. Ten subjects who underwent implantation of electrodes in the nucleus accumbens all experienced relief of symptoms. Half of the subjects had a particularly noticeable response to the stimulation by the electrodes.

"In the current study, we investigated whether these effects last over the long term or whether the effects of the deep brain stimulation gradually weaken in patients," says Prof. Schläpfer. There are always relapses in the case of psychotherapy or drug treatment. Many patients had already undergone up to 60 treatments with psychotherapy, medications and electroconvulsive therapy, to no avail. "By contrast, in the case of deep brain stimulation, the clinical improvement continues steadily for many years." The scientists observed a total of eleven patients over a period of two to five years. "Those who initially responded to the deep brain stimulation are still responding to it even today," says the Bonn psychiatrist, summarizing the results. During the study, one patient committed suicide. "That is very unfortunate," says Prof. Schläpfer. "However, this cannot always be prevented in the case of patients with very severe depression."

he current study shows that the positive effects last for years

Even after a short amount of time, the study participants demonstrated an improvement in symptoms. “The intensity of the anxiety symptoms decreased and the subjects’ drive improved,” reports the psychiatrist. “After many years of illness, some were even able to work again.” With the current publication, the scientists have now demonstrated that the positive effects do not decrease over a longer period of time. “An improvement in symptoms was recorded for all subjects; for nearly half of the subjects, the extent of the symptoms was more than 50 percent below that of the baseline, even years after the start of treatment,” says Prof. Schläpfer. “There were no serious adverse effects of the therapy recorded.”

The long-term effect is now confirmed with the current study. How precisely the electrical stimulation is able to alter the function of the nucleus accumbens is not yet known. “Research is still needed in this area,” says Prof. Schläpfer. “Using imaging techniques, it was proven that the electrodes actually activate the nucleus accumbens.” The deep brain stimulation method may signify hope for people who suffer from the most severe forms of depressive diseases. “However, it will still take quite a bit of time before this therapeutic method becomes a part of standard clinical practice,” says the Bonn scientist.

Provided by University of Bonn 

Source: medicalxpress.com

ScienceDaily (Apr. 3, 2012) — Depressed individuals with a tendency to ruminate on negative thoughts, i.e. to repeatedly think about particular negative thoughts or memories, show different patterns of brain network activation compared to healthy individuals, report scientists of a new study in Biological Psychiatry.

The risk for depression is increased in individuals with a tendency towards negative ruminations, but patterns of autobiographic memory also may be predictive of depression.

When asked to recall specific events, some individuals have a tendency to recall broader categories of events instead of specific events. This is termed overgeneral memory and, like those who tend to ruminate, these individuals also have a higher risk of developing depression.

These self-referential activities engage a network of brain regions called the default mode network, or DMN. Prior studies using imaging techniques have already shown that the DMN activates abnormally in individuals with depression, but the relationship between DMN activity and depressive ruminations was not clear.

In this new report, Dr. Shuqiao Yao of Central South University in Hunan, China and colleagues evaluated DMN functional connectivity in untreated young adults experiencing their first episode of major depression and healthy volunteers. Each participant underwent a brain scan and completed tests to measure their levels of rumination and overgeneral memory.

As expected, the depressed patients exhibited higher levels of rumination and overgeneral memory than did the control subjects. They also observed increased functional connectivity in the anterior medial cortex regions and decreased functional connectivity in the posterior medial cortex regions in depressed patients compared with control subjects.

Among the depressed subjects, an interesting pattern of dissociation emerged. The increased connectivity in anterior regions was positively associated with rumination, while the decreased connectivity in posterior regions was negatively associated with overgeneral memory.

Dr. Yao commented on the importance of these findings: “In the future, resting-state network activity in the brain will provide useful models for investigating network features of cognitive dysfunction in psychopathology.”

"As we dig deeper in brain imaging studies, we are becoming increasingly interested in the activity of brain circuits rather than single brain regions," said Dr. John Krystal, Editor of Biological Psychiatry. “Although it is a more complicated process, studying brain circuits may provide greater insight into symptoms, such as depressive ruminations. The current study nicely illustrates how altered activity at different sites within a brain network may be related to different features of depression.”

Source: Science Daily

April 2, 2012

New research published in the April issue of The Journal of Nuclear Medicine reveals that systemic inflammation causes an increase in depressive symptoms and metabolic changes in the parts of the brain responsible for mood and motivation. With this finding, researchers can begin to test potential treatments for depression for patients that experience symptoms that are related to inflammation in the body or within the brain.

Multiple studies in rodents have shown that inflammation in the body has effects on the brain. This has also been shown in a few human studies—both through measurements of behavioral changes and brain imaging—when subjects were engaged in various computer tasks. The study “Glucose Metabolism in the Insula and Cingulate Is Affected by Systemic Inflammation in Humans,” however, for the first time measured brain activity when subjects were at rest.

"In the study we used F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET), which can accurately measure glucose metabolism in the brain, to determine which brain regions responded to systemic inflammation. Since the subjects were at rest, the changes we observed in the brain can only attributed to systemic inflammation," noted Jonas Hannestad, MD, PhD, lead author of the article.

In the study, nine healthy individuals received a double-blind endotoxin (which elicits systemic inflammation and mild depressive symptoms such as fatigue and reduced social interest) and placebo on different days. After administration, F-18 FDG PET was used to measure the differences in the cerebral metabolic rate of glucose in the insula, cingulate and amygdala regions of the brain. Behavior changes were also primarily assessed on the Montgomery-Asberg Depression Rating Scale (MADRS).

A statistical analysis of the results showed that endotoxin administration was associated with a higher normalized glucose metabolism (NMG) in the insula and lower NMG in the cingulate compared to the placebo; there was no significant difference in the NMG in the amygdala. Seven of nine subjects had an increase in NMG in the insula and a decrease in NMG in the cingulate, and all nine subjects had a decrease in NMG in the right anterior cingulate, suggesting that systemic inflammation induces fundamental physiologic changes in regional brain glucose metabolism. In addition, the MADRS increased for each subject after endotoxin administration, whereas no significant change was noted with the placebo.

Most researchers agree that depression is not a homogeneous disease, but rather that there are multiple mechanisms that can lead to similar symptoms. “If we can show that a subtype of depression is caused in part by inflammation,” said Hannestad, “we can test the ability of treatments that reduce inflammation in only patients in whom we believe inflammation plays a role. In the future, I expect that researchers in this field will be able to develop more precise PET measures that can be used to distinguish between, for instance, a person with ‘inflammatory depression’ and a person with another kind of depression. PET could then be used as diagnostic biomarker to separate subtypes of depression and as a therapeutic biomarker to detect the response to treatment.”

Nearly 17 percent of adults experience depression at some point over their lifetime, with 30.4 percent of cases classified as severe, according to the U.S. National Institute of Mental Health. Fifty-seven percent of adults with depression report receiving treatment in the past 12 months, although 37.8 percent receive minimally adequate treatment.

Provided by Society of Nuclear Medicine

Source: medicalxpress.com

March 21, 2012

What characterizes many people with depression, schizophrenia and some other mental illnesses is anhedonia: an inability to gain pleasure from normally pleasurable experiences.

This image shows VTA dopamine neurons (in red) and VTA GABA fibers (in green). Credit: Stuber Lab, UNC-Chapel Hill.

Exactly why this happens is unclear. But new research led by neuroscientists at the University of North Carolina at Chapel Hill School of Medicine may have literally shined a light on the answer, one that could lead to the discovery of new mental health therapies. A report of the study appears March 22 in the journal Neuron.

The study used a combination of genetic engineering and laser technology to manipulate the wiring of a specific population of brain cells deep in a portion of a midbrain area that’s known to promote behavioral responses to reward.

"For many years it’s been known that dopamine neurons in the ventral midbrain, the ventral tegmental area, or VTA, are involved in reward processing and motivation. For example, they’re activated during exposure to drugs of abuse and to naturally rewarding experiences," said study lead author Garret D. Stuber, PhD, assistant professor in the departments of Psychiatry and Cell and Molecular Physiology, and the UNC Neuroscience Center.

"The major focus in our lab is to determine what other sorts of neural circuits or genetically defined neural populations might be modulating the activity of those neurons, whether it’s increasing or decreasing their activity," Stuber said. "In our study we found that activation of the nearby VTA GABAergic neurons directly inhibit the function of dopamine neurons, which is something that’s never been shown before."

In the past, researchers have tried to get a glimpse into the inner workings of the brain using electrical stimulation or drugs, but those techniques couldn’t quickly and specifically change only one type of cell or one type of connection. But optogenetics, a technique that emerged about six years ago, can. 

In this study, the scientists used a transgenic animal with a foreign gene that has been inserted into its genome to express a bacterial enzyme that can cause DNA recombination only in GABA neurons and not dopamine cells. Using a gene transfer method developed at UNC and with the animal anesthetized, the Stuber team transferred light-sensitive proteins called “opsins” – derived from algae or bacteria that need light to grow – into the VTA, targeting GABA cells. The presence of these foreign opsins in GABA neurons allows researchers to excite or inhibit them by pumping light from a laser into brain tissue.

The animals were then tested in different reward situations, simple tasks in which they were trained to associate a cue with a sugar water reward from a bottle or were given the opportunity to drink the reward by “free licking,” where they could drink as much as they want.

Then, via optical fibers, the researchers shined laser beams onto the genetically manipulated GABA neurons, activating them for 5 seconds during the cue period followed by reward. And on another day, they activated the neurons during reward consumption, when the animals were actively engaged in drinking the sugar water.

"And what we saw when we activated the cells during the cue period, or reward anticipation, it didn’t do anything to the behavioral response at all; they showed no difference compared to non-stimulated animals," Stuber explained.

"And when they were actively engaging with the sucrose, we did see we could disrupt their reward consumption when we activated those cells. They immediately disengaged from drinking, stopped drinking the sucrose solution. And when the stimulus stopped, they would then return back and continue to drink it again."

During the “free licking” sessions, optical stimulation of GABA neurons resulted in disruption of sucrose consumption. The animals stopped drinking.

Using sophisticated electrophysiology and cell chemistry measures, the study team could monitor the activity of the GABA and dopamine neurons. They found a direct link between GABA activation and dopamine suppression.

"So basically, it appears that these GABA neurons located in the VTA are just microns away from dopamine and are negative regulators of dopamine function," Stuber proposes.

"When they become active, their basic job is to suppress dopamine release. A dysfunction in these GABA neurons might potentially underlie different aspects of neuropsychiatric illness, such as depression. Thus, we could think of them as a new physiological target for various aspects of neuropsychiatric diseases."

Provided by University of North Carolina School of Medicine

ScienceDaily (Mar. 7, 2012) — Stimulating the brain with a weak electrical current is a safe and effective treatment for depression and could have other surprise benefits for the body and mind, a major Australian study of transcranial Direct Current Stimulation (tDCS) has found.

Medical researchers from the University of New South Wales (UNSW) and the Black Dog Institute have carried out the largest and most definitive study of tDCS and found up to half of depressed participants experienced substantial improvements after receiving the treatment.

A non-invasive form of brain stimulation, tDCS passes a weak depolarising electrical current into the front of the brain through electrodes on the scalp. Patients remain awake and alert during the procedure.

"We are excited about these results. This is the largest randomised controlled trial of transcranial direct current stimulation ever undertaken and, while the results need to be replicated, they confirm previous reports of significant antidepressant effects," said trial leader, Professor Colleen Loo, from UNSW’s School of Psychiatry.

The trial saw 64 depressed participants who had not benefited from at least two other depression treatments receive active or sham tDCS for 20 minutes every day for up to six weeks.

"Most of the people who went into this trial had tried at least two other antidepressant treatments and got nowhere. So the results are far more significant than they might initially appear — we weren’t dealing with people who were easy to treat," Professor Loo said.

Significantly, results after six weeks were better than at three weeks, suggesting the treatment is best applied over an extended period. Participants who improved during the trial were offered follow up weekly ‘booster’ treatments, with about 85 percent showing no relapse after three months.

"These results demonstrate that multiple tDCS sessions are safe and not associated with any adverse cognitive outcomes over time," Professor Loo said, adding tDCS is simple and cost effective to deliver, requiring a short visit to a clinic.

The study also turned up additional unexpected physical and mental benefits, including improved attention and information processing.

"One participant with a long-standing reading problem said his reading had improved after the trial and others commented that they were able to think more clearly.

"Another participant with chronic neck pain reported that the pain had disappeared during the trial. We think that is because tDCS actually changes the brain’s perception of pain. We believe these cognitive benefits are another positive aspect of the treatment worthy of investigation," Professor Loo said.

The researchers are now looking at an additional trial to include people with bipolar disorder, with early results from overseas suggesting tDCS is just as effective in this group.

Source: Science Daily

March 6, 2012

Getting rid of a protein increases the birth of new nerve cells and shortens the time it takes for antidepressants to take effect, according to an animal study in the March 7 issue of The Journal of Neuroscience. The protein, neurofibromin 1, normally helps prevent uncontrolled cell growth. The findings suggest therapeutic strategies aimed at stimulating new nerve cell birth may help treat depression better than current antidepressants that commonly take several weeks to reach full efficacy.

Throughout life, a section of the hippocampus — the brain’s learning and memory center — produces new nerve cells. This process, called neurogenesis, is made possible by specialized cells called neural progenitor cells (NPCs). While previous studies show adult neurogenesis declines with age and stress, therapies known to alleviate symptoms of depression, such as exercise and antidepressants, increase neurogenesis.

In the new study, a team of scientists directed by Luis Parada, PhD, of the University of Texas Southwestern, examined neurogenesis after deleting the neurofibromin 1 (Nf1) gene from NPCs in adult mice. Removal of Nf1 increased the number and maturation of newborn nerve cells in the adult hippocampus. Nf1 mutant mice showed reductions in depressive- and anxiety-like behaviors following 7 days of antidepressant treatment, whereas mice without the mutation took longer to show improvements.

"Our findings establish an important role for Nf1 in controlling neurogenesis in the hippocampus and demonstrate that activation of adult NPCs is enough to regulate depression- and anxiety-like behaviors," said study co-author Renee McKay, PhD, of the University of Texas Southwestern. "Our work is among the first to demonstrate the feasibility of altering mood via direct manipulation of adult neurogenesis," McKay added.

To determine if deleting Nf1 in adult NPCs leads to long-term behavioral changes in mice, the scientists ran 8-month-old mice through a battery of tests designed to measure anxiety- and depressive-like behaviors. Compared with other mice, the mutant mice showed less signs of anxiety and demonstrated resistance to the effects of chronic mild, unpredictable stress. The finding shows even without antidepressants, the deletion of Nf1 from NPCs in adult mice decreases symptoms of depression and anxiety.

"This study demonstrates that inducing neurogenesis is sufficient to produce antidepressant behavioral actions, and provides novel targets for therapeutic interventions," said Ronald Duman, PhD, a neurogenesis expert from Yale University.

Provided by Society for Neuroscience

Source: medicalxpress.com

ScienceDaily (Feb. 27, 2012) — Most of us know what it means when it’s said that someone is depressed. But commonly, true clinical depression brings with it a number of other symptoms. These can include anxiety, poor attention and concentration, memory issues, and sleep disturbances.

Brain hyperactivity. Maps showing the difference in the strength of brain connections between depressed subjects (left) and controls (right). Depressed subjects show much stronger connections, as evidenced by red colors in their maps. (Credit: Image courtesy of University of California - Los Angeles)

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February 6, 2012