Brain implants have long-lasting effect on depression


Deep-brain stimulation involves implanting electrodes in parts of the brain.

Depressed patients who are resistant to other therapies can be helped long term by deep-brain stimulation. The effects can still be seen six years after implanting stimulating electrodes deep inside the brain, according to a follow-up of patients published online in the American Journal of Psychiatry.

The study was carried out by a team led by psychiatrist Sidney Kennedy and neurosurgeon Andres Lozano at the University Health Network in Toronto, Canada.

They show that, within a year of implantation, depression lifted in 12 of 20 patients — and that the benefits were sustained for up to six years. But two of the patients died by presumed suicide.

The good news is that those who showed an early response to deep-brain stimulation maintained that response, says Kennedy. “However the suspected suicides indicate that we have not been able to prevent the course of illness,” he adds.

According to Thomas Schläpfer, a psychiatrist at the University of Bonn, Germany, the study shows that deep-brain stimulation does actually seem to modify the disease, something that no other treatment has done. “Medication studies in depression always show patients relapsing, even if they respond at first — but responders in this study did not relapse.” In the paper, response is defined as a decrease by 50% or more in scores on the Hamilton rating scale for depression.

Improvement, not cure

Patients seemingly helped by anti-depression medication also sometimes attempt suicide, says Schläpfer. “Improvements in symptoms of depression doesn’t mean a patient is no longer depressed at all.”

The 20 patients in the deep-brain stimulation trial were at particularly high risk of suicide, having failed to respond to four different treatments, including psychotherapy, drug therapy or electroconvulsant therapy. On average, they had been seriously depressed for 20 years. “Between 15 and 30% of such treatment-resistant patients commit suicide,” says Kennedy.

“But most of those who responded to the deep-brain stimulation were well enough to embark on paid employment,” he adds. Responders began to undertake and enjoy social interactions and reported having a better quality of life. “When some patients complained that they had lost the effect, we found that the batteries feeding their electrodes had simply run down,” says Kennedy. “The effect came back shortly after we replaced the batteries.”

Schläpfer has conducted a long-term study of 13 treatment-resistant patients together with neurosurgeon Volker Sturm from the University of Cologne, Germany, which targeted a slightly different site in the brain. It is not yet published, but the results are similar, he says. One patient committed suicide, but six responded and continue to respond.

Both of these studies are pilots and were not placebo-controlled. Double-blind, placebo-controlled trials involving 40 patients are being launched by Health Canada. In half the patients, newly implanted electrodes will remain switched off for the first few months, with neither patient nor psychiatrist knowing whether electrodes are on or off in individual patients.

Two electrode manufacturers, Medtronic, headquartered in Minneapolis, Minnesota, and St Jude Medical of Little Canada, Minnesota, are planning to begin similar trials in the United States.

source: medicine medicine

Antipsychotic drugs could shrink patients’ brains

Experts say findings should not dramatically change current prescription practices.

Coloured magnetic resonance imaging (MRI) scan of the brain from the side, combined with a coloured neck and skull X-ray.
The implications of the finding that antipsychotic drugs may reduce the size of patients’ brains are not clear.SOVEREIGN, ISM / SCIENCE PHOTO LIBRARY

Evidence that prescription drugs shrink patients’ brains would, one might think, suggest only one course of action: stop prescribing them. But the matter turns out to be much more complicated, according to research published today in Archives of General Psychiatry on the effects of antipsychotic drugs in people with schizophrenia1.

In the past 15 years, research has indicated that people with schizophrenia have smaller cerebral volumes than the general population, and that this reduction is particularly large in ‘grey-matter’ structures, which contain the cell bodies of neurons. For instance, one meta-analysis points to 5–7% reductions in the size of the amygdala, hippocampus and parahippocampus2, which are all involved in memory storage and retrieval.

But scientists have debated whether the decrease is caused by the disease alone, or whether powerful antipsychotic drugs also have a role. According to the latest findings, the more antipsychotics patients receive, the more likely they are to have a decreased amount of grey matter.

The research was led by Beng Choon Ho, a psychiatrist and neuroscientist at the University of Iowa in Iowa City. His team used magnetic resonance imaging (MRI) to scan the brains of 211 patients, administering on average 3 scans per patient over a 7.2-year period1. They found that treatment length and the type and dose of antipsychotic drugs taken were both relatively good predictors of total brain volume change. Use of antipsychotics explained 6.6% of the change in total brain volume and 1.7% of the change in total grey-matter volume.

The study developed from a previous work in which Ho’s team analysed the contribution of a genetic variation to grey-matter volume reduction3. In the latest work, the researchers looked again at those results and added data from more patients. This time, they examined the contribution from the dose of antipsychotics prescribed. They found that the greatest reduction came in those who had been recently diagnosed — and so would have just started taking the medications. “We did not expect to see this,” says Ho.

Ho says that the effect is “small but significant”. He adds, “We have been looking at the data for five years. We’ve been very careful to get it right because of the potential implications.”

Missing control

The scale of the study is impressive, says Andreas Meyer-Lindenberg, a neuroscientist at the University of Heidelberg in Mannheim, Germany. “It’s by far the largest sample studied longitudinally. And there was a great follow-up and retention rate,” he says. Stefan Borgwardt, a neuropsychiatrist at the University of Basel, Switzerland, says that the study “will definitely have a great impact, not only on the field of schizophrenia research but also on clinical practice”.

Animal studies support the link. David Lewis, a neuroscientist and psychiatrist at the University of Pittsburgh, Pennsylvania, found that healthy non-human primates, given doses of antipsychotics similar to those given to humans, showed brain volume reductions of around 10%, mostly attributable to loss of the glial cells that support and protect neurons4,5.

But Lewis, who has written an editorial to accompany Ho’s study6, warns that his own, Ho’s and other studies are “convergent but still circumstantial”. It is impossible to distinguish the effect of the disease from that of the drug, he says, because “both are changing over time”.

Ho acknowledges that his study is marred by the lack of a placebo control group — for ethical reasons, patients cannot be deprived of the medications they need — and the lack of ‘within individual’ studies in which the same patient either uses or does not uses the drugs. “It’s not the ideal study design, but as good as we could ever get with something like this,” says Ho.

Meyer-Lindenberg warns against over-interpreting MRI data, which can be affected by confounding factors including lifestyle, smoking and socioeconomic differences. “Although it does address them as far as possible statistically, this study cannot exclude them,” he says. Meyer-Lindberg himself published a study last year showing that antipsychotics cause quickly reversible changes in brain volume that do not reflect permanent loss of neurons

Bigger and better?

The idea that decreased brain volumes are necessarily bad is also controversial. Borgwardt says that small cerebral volumes are generally thought to lead to worse brain function, and some studies show that the greater the decrease, the worse the illness outcome. Antipsychotics have long been known to have side effects — notably uncontrolled tremors (parkinsonism) and restless leg syndrome (akathisia) — that might be explained by reduction in brain volume.

But decreasing brain volume could also be responsible for the beneficial effects of the drugs. Lewis points out that the reduction is greatest in patients who stay on the drugs the longest — meaning, presumably, that they are getting the best benefit and suffering relatively few side effects.

In the brains of adolescents, volume loss has been shown to reflect maturation through the elimination of superfluous synapses, says Meyer-Lindenberg.

Borgwardt has begun to scan the brains of people at high risk of developing schizophrenia and track the cerebral volume of those who go on to be treated8, a strategy that, on a larger scale, could help to clarify the controversy. An alternative route could be to study people with depression and bipolar disorder, says Lewis. Comparing changes in the brain volume of such patients who use antipsychotics with those that do not would help to tease out the relative contribution of the drugs.

In the meantime, Ho’s study and others should strengthen doctors’ commitments to use antipsychotic drugs sparingly, say all the researchers contacted by Nature. “We stated as clearly as possible that we are not advocating that people stop taking medications. A large body of evidence shows the drugs relieve symptoms and prevent relapse,” says Ho. “But this will reinforce what I have always tried to do with my patients — work with them in finding the lowest effective dose.”

source: nature medicine

Botulinum toxin injections for low-back pain and sciatica

Adequate relief from low-back pain (LBP) is not always possible. Emerging evidence suggests a role for botulinum neurotoxin (BoNT) injections in treating pain disorders. Proponents of BoNT suggest its properties can decrease muscle spasms, ischemia and inflammatory markers, thereby reducing pain.
OBJECTIVES: To determine the effects of botulinum toxin injections in adults with LBP.
SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library 2009, issue 3) and MEDLINE, EMBASE, and CINAHL to August 2009; screened references from included studies; consulted with content experts and Allergan. We included published and unpublished randomised controlled trials without language restrictions
SELECTION CRITERIA: We included randomised trials that evaluated BoNT serotypes versus other treatments in patients with non-specific LBP of any duration.
DATA COLLECTION AND ANALYSIS: Two review authors selected the studies, assessed the risk of bias using the Cochrane Back Review Group criteria, and extracted the data using standardized forms. We performed a qualitative analysis due to lack of data.
MAIN RESULTS: We excluded evidence from nineteen studies due to non-randomisation, incomplete or unpublished data. We included three randomised trials (N =123 patients). Only one study included patients with chronic non-specific LBP; the other two examined unique subpopulations. Only one of the three trials had a low risk of bias and demonstrated that BoNT injections reduced pain at three and eight weeks and improved function at eight weeks better than saline injections. The second trial showed that BoNT injections were better than injections of corticosteroid plus lidocaine or placebo in patients with sciatica attributed to piriformis syndrome. The third trial concluded that BoNT injections were better than traditional acupuncture in patients with third lumbar transverse process syndrome. Both studies with high risk of bias had several key limitations. Heterogeneity of the studies prevented meta-analysis. There is low quality evidence that BoNT injections improved pain, function, or both better than saline injections and very low quality evidence that they were better than acupuncture or steroid injections.
AUTHORS’ CONCLUSIONS: We identified three studies that investigated the merits of BoNT for LBP, but only one had a low risk of bias and evaluated patients with non-specific LBP (N = 31). Further research is very likely to have an important impact on the estimate of effect and our confidence in it. Future trials should standardize patient populations, treatment protocols and comparison groups, enlist more participants and include long-term outcomes, cost-benefit analysis and clinical relevance of findings.

source: cochrane library

Brain Scan Can Tell if You’ll Quit Smoking

Researchers have found a way to predict how successful a smoker will be at quitting by using an MRI scan to look for activity in a region of the brain associated with behavior change.

The scans were performed on 28 heavy smokers who had joined an anti-smoking program, according to the study published Monday in the peer-reviewed journal Health Psychology.

Participants were asked to watch a series of commercials about quitting smoking while a magnetic resonance imaging machine scanned their brains for activity.

After each ad, subjects in the study “rated how it affected their intention to quit, whether it increased their confidence about quitting, and how much they related to the message,” researchers explained.

Those who showed activity in the medial prefrontal cortex during the ads were “significantly linked to reductions in smoking behavior” in the month that followed, regardless of how the people said they were affected by the ad.

“What is exciting is that by knowing what is going on in someone’s brain during the ads, we can do twice as well at predicting their future behavior, compared to if we only knew their self-reported estimate of how successful they would be or their intention to quit,” said lead author Emily Falk.

“It seems that our brain activity may provide information that introspection does not,” added Falk, director of the Communication Neuroscience Laboratory at the University of Michigan.

She said researchers would next try to determine which kind of messages were most effective by matching brain activity to the ads.

The study was funded by the National Institutes of Health and the National Science Foundation, and took place at University of California, Los Angeles.

source: the international journal of psychology

Back Pain May Be Inherited

Study Suggests Role for Genes in Painful Disc Disorders
woman holding lower back

Feb. 4, 2011 — If you suffer from persistent low back pain, your genes may bear some of the blame.

Just like eye color and baldness, the likelihood of developing low back pain from disc disease may be inherited, a new study shows.

When researchers analyzed health and family history data for 2 million Utah residents, they identified 1,264 with a diagnosis of lower spine disease associated with herniated or degenerating discs. Disc disease is one of  the most common causes of persistent low back pain.

People with an immediate family member, such as a parent, sibling, or child, with disc-related low back pain were more than four times more likely to have low-back pain themselves.

More modest increases in risk were associated with having a second- or even a third-degree relative with a diagnosis of herniated or degenerative disc disease.

This finding was particularly relevant because these more distant relatives were less likely than first-degree relatives to share the same environmental risk factors for low-back pain.

“While not 100% conclusive, this is very strong evidence that there is a genetic component to disc degeneration and disc herniation,” study researcher  Alpesh A. Patel, MD, of Salt Lake City’s University of Utah School of Medicine, tells WebMD.

Back Pain All in the Family

Just about everyone experiences sporadic back pain at some point in their lives, but most people get better with little treatment after a few days or weeks.

Patel says it is common for complaints of persistent back pain to run in families, but the reasons for this have not been clear.

“Patients with back pain often tell me that their dad or granddad had it too, but it may be that they were in the same line of work or played the same high-impact sports,” he says.

Patel and colleagues were able to track low-back-related disease within families thanks to a unique registry known as the Utah Population Database, which contains both health and genealogic information for 2.4 million residents of the state.

One puzzling aspect of disc-related low back disease is that some people with herniated or degenerating discs suffer excruciating pain and other people experience no pain at all.

Pain Perception May Be Driven by Genes

In the University of Utah study, there appeared to be a genetic component to whether disc disease caused symptoms.

“We really can’t say from this study if people who are genetically predisposed have more disc problems or if they just experience more pain,” Patel says.

A growing body of research suggests that susceptibility to pain is inherited, although no actual pain genes have been identified, he adds.

Back surgeon Daryll C. Dykes, MD, PhD, tells WebMD that he is not surprised by the findings from the Utah study.

Dykes is a spokesman for the American Academy of Orthopaedic Surgeons and a surgeon with the Twin Cities Spine Center in Minneapolis.

“We have had strong suspicions that genes are a factor in low back pain, but we haven’t had good scientific studies to back that up,” he says.

He says people with a family history of low back pain can lower their risk by maintaining a healthy weight, performing cardiovascular and core strengthening exercises, and not smoking.

source: webMD

Race, Sex, and Clinical Outcomes in Early HIV Infection

In the U.S., nonwhite women from the South had the worst outcomes of any group analyzed.

Previous studies have shown that, in established HIV infection, women have lower viral loads and higher CD4-cell counts than men, and nonwhites have lower viral loads than whites. Do these differences by race and sex influence clinical presentations and outcomes during early HIV infection?

To find out, researchers evaluated longitudinal data from 2277 individuals who were diagnosed with acute or recent HIV infection between 1997 and 2007. Women made up only 5% of the cohort, and 55% of them were nonwhite. In contrast, only 23% of the men were nonwhite. Most participants were from the western or midwestern U.S., but 45% of the nonwhite women were from southern states. No information was available on hepatitis coinfection, insurance coverage, income, education, or mental health. Mean follow-up time was approximately 4 years.

As expected, women had lower baseline viral loads and higher baseline CD4-cell counts than men. However, these differences disappeared within 2 years among individuals who had not yet initiated antiretroviral therapy (ART). The proportion of patients who started ART during the study period was similar between men and women (69% and 64%), as was the proportion who achieved virologic suppression within 6 months of ART initiation (81% and 77%). However, rates of ART initiation differed significantly by race and geographic location: Nonwhite men and women were less likely to start ART than white men, who were, in turn, less likely to start ART than white women. Patients from the South were less likely to start ART than those from other regions.

Women were more likely than men to report HIV-associated non–AIDS-related conditions (persistent generalized lymphadenopathy, diarrhea, peripheral neuropathy) and certain AIDS-defining illnesses (recurrent bacterial pneumonia). Of all the groups analyzed, nonwhite women in the South had the highest rate of HIV/AIDS-related events (81%).

Comment: The data presented in this paper open the door for further investigation into the influence of biology on the course of HIV infection. However, removing sociodemographic barriers to optimal care will likely have a much greater impact on outcomes than understanding biological determinants of progression and response to treatment.

Sonia Nagy Chimienti, MD

Published in Journal Watch HIV/AIDS Clinical Care February 7, 2011