BROADEN Study on DBS for Depression by St. Jude to be expanded

The FDA has allowed St. Jude to expand its BROADEN study to up to 20 study centers across the US with a total of 125 patients, the company has announced that they later request approval to further expand the study to a total of 231 patients. You nan read the press release of the company here.

Doctors push for brain surgery to treat depression

An interesting development from down under:

"Deep brain stimulation has been used to treat patients with Parkinson's disease for decades, but more recently it has been trialled on patients with severe depression and some brain surgeons want the procedure to be made more widely available."

Read it here.

Synaptic potentiation onto habenula neurons in the learned helplessness model of depression

This paper demonstrates that presynaptic action on neurons of the lateral habenula contribute to the learned helplessness model of depression in rodents, read it here.

Deep brain stimulation: Experts raise alarms about aggressive marketing

An article in the Harvard Health Blog discussing the Health Affairs paper and its write up in the New York Times. Read it here.

Wariness on Surgery of the Mind

A very balanced and thoughtful article written by Benedict Carey in the NYTimes on a paper which appeared in the February issue of Health Affairs. This paper makes some ethical arguments regarding the use of the Humanitarian Device Exemption for DBS in Obsessive-Compulsive Disorder.

Brain implants have long-lasting effect on depression

Allison Abbott writes in naturenews on long-term outcomes of cg25 DBS for Major Depression, read it here.

Cross-species affective functions of the medial forebrain bundle—Implications for the treatment of affective pain and depression in humans

A paper which appeared in Neuroscience & Biobehavioral Reviews reports data showing that all currently researched DBS targets for depression - which all lead to comparable response rates in patient populations with comparable treatment refractoriness - actually stimulate in close proximity to the medial forebrain bundle (MFB) pointing to the possibility that this structure might be involved in mediating antidepressant effects. Full reference below.

Volker A. Coenen, Thomas E. Schlaepfer, Burkhard Maedler, Jaak Panksepp. Cross-species affective functions of the medial forebrain bundle—Implications for the treatment of affective pain and depression in humans. Neuroscience & Biobehavioral Reviews, 2010; DOI: 10.1016/j.neubiorev.2010.12.009

Brain Pacemakers: A Long-Lasting Solution in the Fight Against Depression?

A report on a putative new DBS target - the medial forebrain bundle - for depression, read it here. It refers to a recent paper in Neuroscience & Biobehavioral Reviews titled Cross-species affective functions of the medial forebrain bundle—Implications for the treatment of affective pain and depression in humans.

Deep brain stimulation surgery 'first' for depression

This is a press release on a program which was broadcasted by the BBC January 24, 2011. They (the journalists) claim that this is the 'first' use of DBS for depression (I hope that the investigators don't). Read the release and watch the video here.

Vagus Nerve Stimulation (VNS) and Treatment of Depression: To the Brainstem and Beyond

PMID: 21103178

AUTHORS: John P O'Reardon, Pilar Cristancho, Andrew D Peshek

REFERENCE: Psychiatry (Edgmont) 2006 May 3(5):54-63

Neuromodulation appears to be emerging gradually as a new therapeutic
field in psychiatric treatment. It encompasses neuropsychiatric medical
devices, such as vagus nerve stimulation (VNS), transcranial magnetic
stimulation (TMS), deep brain stimulation (DBS), and electroconvulsive
therapy (ECT). As a therapeutic approach to affective disorders,
neuromodulation shifts the focus from the monoamine synapse to neural
circuitry of the brain, which is dysregulated in depression. This neural
circuitry has been elaborated on over the course of 15 years of
neuroimaging research in mood disorders and is now believed to encompass
disturbances in a frontolimbic network. These include reduced
metabolism and blood flow in the prefrontal cortex and anterior
cingulate and pathologically increased activity in the subgenual
cingulate and amygdala.VNS is an implanted device that has established
efficacy in pharmaco-resistant epilepsy. It was approved by the FDA for
the treatment of severe, recurrent unipolar and bipolar depression in
July of 2005. VNS adopts a bottom-up approach to modulating the neural
circuitry of depression by stimulating vagal afferent fibers in the neck
, which carry impulses to the brain stem to target there the locus
ceruleus and dorsal raphe nucleus. Now that VNS has moved beyond the
experimental phase and into the clinic, psychiatrists are faced with
deciding who is an appropriate patient for this surgical implant and how
to integrate VNS into existing treatment in order to optimize both
efficacy and safety.This review of VNS will assess the efficacy and
safety data that led to the FDA approval. We will also review for the
busy clinician how VNS is likely to translate into clinical practice as
a treatment option for patients in need who are suffering from severe
depression.

Optogenetics: Controlling the Brain with Light

A wonderfully written, easy to understand paper on Optogenetics, written by the expert, Karl Deisseroth Access the article here.

Electrical engineering fixes brain's circuit board

An article in the NewScientist reviewing results from studies of DBS for Depression.

Editorial: Deep brain electrodes are real hope for mental illness

Deep Brain Stimulation Mechanisms in Depression

An interesting analysis by way of the AL FIN Blog:

DBS involves continually delivering high-frequency pulses of weak current to a particular region via stimulators that are surgically inserted into the brain. Although invasive, it works so well for Parkinson's disease and other movement disorders that it is now mainstream, with tens of thousands of patients implanted.

In the last decade, researchers have tested DBS on a variety of other conditions. It has proved effective at reducing some symptoms of bipolar disorder and Tourette's syndrome (see table). It was recently approved by the US Food and Drug Administration to treat obsessive compulsive disorder. _NS

The effect of deep brain stimulation (DBS) on a depressed brain is turning out to be more complex than at first thought. DBS is not merely affecting the part of the brain near the electrode. DBS appears to be affecting entire circuits of brain interaction -- performing a type of fine-tuning or calibration of the circuitry.

The researchers implanted the stimulators into the subgenual area, which is involved in emotion, in six severely depressed patients for whom all other treatments had failed, including several types of antidepressant drugs and electroconvulsive therapy. Four reported vast improvements (Neuron, vol 45, p 651).

The region was selected because brain imaging studies had shown it to be hyperactive in many people with depression. Most researchers thought that DBS worked by silencing activity in that area. This would explain why so many patients responded as soon as their stimulators were switched on: many said the operating room looked brighter than when they had gone in, for example, a sign of a changed outlook on life. It was as if "something painful had suddenly stopped", Mayberg said at a recent lecture on her work at the Massachusetts Institute of Technology.

That wasn't the whole story, however. PET scans revealed that while DBS damped down activity in the subgenual area as expected, other regions appeared affected too, particularly parts of the nearby prefrontal cortex, which is involved in decision-making and evaluating emotions. "We got lucky," says Mayberg. "It worked, but probably not for the reason we thought."

...His [Thomas Schlaepfer] team used DBS on the nucleus accumbens, an area involved in assessing pleasurable stimuli that is known to behave abnormally in depression (Biological Psychiatry, DOI: 10.1016/j.biopsych.2009.09.013).

PET scans of seven of the patients revealed that the implant didn't seem to affect activity in the nucleus accumbens itself, but instead suppressed the subgenual area - also called Brodmann's area 25 - just as with Mayberg's team (see diagram). It also had reverberations in parts of the prefrontal cortex.

"There are clear connections between area 25 and the nucleus accumbens," Schlaepfer says. He suspects that the three areas are part of a brain network that his and Mayberg's teams both tapped into.

The experiments also raise the question of why DBS doesn't work in everyone. While all of Schlaepfer's patients felt their lives had improved a year after having the stimulator implanted - be it returning to work, taking up a hobby or making new friends - some fared much better than others.

...That's where Mayberg's most recent results, which she presented at the MIT lecture, come in. To see if there were any pre-existing differences in the brains of DBS responders and non-responders, which might predict who should go to the trouble of getting a DBS implant, Mayberg's team turned to functional MRI, which allows you to see which regions light up at the same time - indicating that they are "connected".

In depressed patients who went on to respond to DBS, a part of their prefrontal cortex tended to light up in conjunction with the subgenual area. This did not happen in non-responders. In these patients, the amygdala, which is involved in fear and other emotions, tended to be connected to the subgenual area - not the case in responders. _NS

One of the aims of psycho-neurologists at the Al Fin Institutes of Psycho-Neurology, is to place the diagnoses of mental disorders on a sound scientific foundation. The demonstration of physical changes in brain circuits as a result of successful treatment would go a long way toward making the treatment of mental disorders more respectable within medicine and society.

St. Jude Medical Awarded U.S. Patent For Neurostimulation Therapy For Depression

St. Jude Medical, Inc. (NYSE:STJ) announced it has been awarded a patent from the U.S. Patent and Trademark Office conducive to treating depression using neurostimulation psychotherapy in an arena of the intellectual known as Brodmann Area 25.

Brodmann Close 25 is a organization within the subcollosal gyrus region of the brain. It is the focus of the St. Jude Medical BROADEN(TM) (BROdmann Neighbourhood 25 DEep brain Neuromodulation) muse about, which is evaluating whether deep sense stimulation (DBS) cure can workers people who suffer from major depressive disorder, a dire form of impression. This study is being conducted under a U.S. Scoff and Dose Administration (FDA) Investigational Device Exemption (IDE), which was announced in February 2008.

“This patent is a cornerstone in developing our passage to lost brain stimulation fitted depression, which is the leading belief of disability in the U.S. come up to b become illnesses,” said Chris Chavez, president of St. Jude Medical’s ANS Division. “The BROADEN study provides hope respecting a sober new psychotherapy to the millions of patients still seeking treatment for their critical concavity.”

On April 4, St. Jude Medical enrolled the first unfailing, a woman from Chicago, in the BROADEN study. The patient will be implanted with the Libra(R) Deep Thought Stimulation Methodology, an investigational device, at Alexian Brothers Behavioral Condition Sanatorium in Chicago.

“There is a tremendous need for inquire into in the area of major depressive disorder, distinctively among those who have weak other treatment options,” said Anthony D’Agostino, M.D., medical director of Alexian Brothers Behavioral Health Hospital and the prima donna investigator at the writing-room site. “We hope that our participation in the study inclination combine to the centre of research previously conducted for patients hardship from dent and, if possible, shed some clarification on what type of patient is most likely to benefit.”

Co-investigators at Alexian Brothers Behavioral Health Infirmary are psychiatrists Greg Teas, M.D., Slash Lerman, M.D. and neurosurgeon Konstantin Slavin, M.D.

The BROADEN inspect is a controlled, multi-install, blinded, clinical enquiry of deeply brain stimulation in the U.S. It will build upon the pioneering depression work conducted at the University of Toronto by a research team led by neurologist Helen S. Mayberg, M.D. (now with Emory University School of Medicine) and neurosurgeon Andres Lozano, M.D.

The Libra Deep Brain Stimulation System, which is being evaluated in this sanctum sanctorum, is designed to deliver mild pulses of common from a device implanted next-door the collarbone and connected to small electrical leads placed at specific targets in the brain.

In the U.S., more than 21 million adults suffer from some kind of depressive disorder, according to the National Alliance of Mental Health. Since barely approximately 80 percent can be effectively treated with currently available therapies, approaching 4 million matured Americans spend with despair that does not respond to medications, psychotherapy or electroconvulsive therapy. The World Health Organization estimates that depression affects thither 121 million people worldwide.

For more news apropos this study, call toll-free 866-787-4332 or visit http://www.BROADENstudy.com.

St. Jude Medical

Treating Depression by Stimulating the Pleasure Center

Philadelphia, PA, 26 January 2010 - Even with the best of available treatments, over a third of patients with depression may not achieve a satisfactory antidepressant response. Deep brain stimulation (DBS), a form of targeted electrical stimulation in the brain via implanted electrodes, is now undergoing careful testing to determine whether it could play a role in the treatment of patients who have not sufficiently improved during more traditional forms of treatment.

A major challenge of this work is determining the best region of the brain to stimulate. Some researchers stimulate the subgenual prefrontal cortex, a brain region implicated in depressed mood states, while others stimulate a region called the “anterior limb of the internal capsule”, a nerve pathway that passes through the basal ganglia, a lower brain region. Physicians publishing a new report in Biological Psychiatry now describe findings related to the stimulation of the nucleus accumbens, a brain region the size of a hazelnut associated with reward and motivation that is implicated in processing pleasurable stimuli, sometimes referred to as the “pleasure center” of the brain. The inability to experience pleasure is a key symptom of depression and previous studies have shown that functioning of the nucleus accumbens is impaired in depressed individuals.

Bewernick and colleagues administered DBS treatment in ten patients with severe long-term depression who had not responded to multiple other antidepressant treatments, including psychotherapy, drug treatments and electroconvulsive treatment. After one year of DBS, all patients showed some improvement, and half of them experienced significant improvement in their symptoms of depression, astonishing considering they had not responded to any prior antidepressant treatment. In addition, the patients showed reduced ratings of anxiety and had only minor side effects. Importantly, none of their overall brain functioning was impaired by the DBS treatment.

“The nucleus accumbens is a brain region that animals will seek to stimulate even if they do not appear depressed and this is one reason that it is sometimes referred to as a reward center. It is interesting to note that the patients in this study did not simply feel stimulated or euphoric; instead, there appeared to be reductions in depressed mood that paralleled an increase in the capacity for pleasure,” commented Dr. John Krystal, Editor of Biological Psychiatry. “This finding will stimulate further study on the role of the nucleus accumbens in depression and its treatment.”

The authors caution that because they studied only a small number of people, further research is necessary before DBS could be considered a clinically useful treatment for treatment-resistant depression. There are also important ethical considerations, since DBS treatment first requires potentially risky brain surgery. However, these preliminary findings are promising that DBS may provide relief to individuals with severe treatment-resistant depression.

# # #

Notes to Editors:
The article is “Nucleus Accumbens Deep Brain Stimulation Decreases Ratings of Depression and Anxiety in Treatment-Resistant Depression” by Bettina H. Bewernick, René Hurlemann, Andreas Matusch, Sarah Kayser, Christiane Grubert, Barbara Hadrysiewicz, Nikolai Axmacher, Matthias Lemke, Deirdre Cooper-Mahkorn, Michael X. Cohen, Holger Brockmann, Doris Lenartz, Volker Sturm, and Thomas E. Schlaepfer. At the University Hospital in Bonn, Germany, authors Bewernick, Hurlemann, Matusch, Kayser, Grubert, Hadrysiewicz, Axmacher, Cooper-Mahkorn, and Schlaepfer are affiliated with the Department of Psychiatry and Psychotherapy, with Axmacher also with the Department of Epileptology, while Brockmann is with the Department of Nuclear Medicine. Schlaepfer is also with the Departments of Psychiatry and Mental Health, Johns Hopkins University, Baltimore, Maryland. Lenartz and Sturm are affiliated with the Department of Functional Neurosurgery, University Hospital, Cologne, Germany. Cohen is from the Department of Psychology, University of California, Davis, California. Lemke is with the Department of Psychiatry, Hospital Alsterdorf, Hamburg, Germany.

The article appears in Biological Psychiatry, Volume 67, Issue 2 (January 15, 2010), published by Elsevier.

The authors’ disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D. is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available at

http://journals.elsevierhealth.com/webfiles/images/journals/bps/Biological_Psychiatry_Editorial_Disclosures_08_01_09.pdf.

Full text of the article mentioned above is available upon request. Contact Maureen Hunter at m.hunter@elsevier.com to obtain a copy or to schedule an interview.

About Biological Psychiatry

This international rapid-publication journal is the official journal of the Society of Biological Psychiatry. It covers a broad range of topics in psychiatric neuroscience and therapeutics. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and treatment of major neuropsychiatric disorders. Full-length and Brief Reports of novel results, Commentaries, Case Studies of unusual significance, and Correspondence and Comments judged to be of high impact to the field are published, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Concise Reviews and Editorials that focus on topics of current research and interest are also published rapidly.

Biological Psychiatry is ranked 4th out of the 101 Psychiatry titles and 14th out of 219 Neurosciences titles on the 2008 ISI Journal Citations Reports® published by Thomson Scientific.

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Nucleus Accumbens Deep Brain Stimulation Decreases Ratings of Depression and Anxiety in Treatment-Resistant Depression

Biological Psychiatry
Volume 67, Issue 2, 15 January 2010, Pages 110-116

Stimulating Research on the Treatment of Depression: Electroconvulsive Therapy, Transcranial Magnetic Stimulation, and Deep Brain Stimulation
doi:10.1016/j.biopsych.2009.09.013 | How to Cite or Link Using DOI
Copyright © 2010 Society of Biological Psychiatry Published by Elsevier Inc.
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Archival Report

Nucleus Accumbens Deep Brain Stimulation Decreases Ratings of Depression and Anxiety in Treatment-Resistant Depression
Bettina H. Bewernick^a, René Hurlemann^a, Andreas Matusch^a, Sarah Kayser^a, Christiane Grubert^a, Barbara Hadrysiewicz^a, Nikolai Axmacher^{a, d}, Matthias Lemke^g, Deirdre Cooper-Mahkorn^a, Michael X. Cohen^e, Holger Brockmann^f, Doris Lenartz^c, Volker Sturm^c and Thomas E. Schlaepfer^{a, b,}

a Department of Psychiatry and Psychotherapy, University Hospital, Bonn, Germany
b Departments of Psychiatry and Mental Health, The Johns Hopkins University, Baltimore, Maryland
c Department of Functional Neurosurgery, University Hospital, Cologne, Germany
d Department of Epileptology, University Hospital, Bonn, Germany
e Department of Psychology, University of California, Davis, California
f Department of Nuclear Medicine, University Hospital, Bonn, Germany
g Department of Psychiatry, Hospital Alsterdorf, Hamburg, Germany

Received 9 July 2009; revised 3 September 2009; accepted 11 September 2009. Available online 14 November 2009.

Background
While most patients with depression respond to combinations of pharmacotherapy, psychotherapy, and electroconvulsive therapy (ECT), there are patients requiring other treatments. Deep brain stimulation (DBS) allows modulation of brain regions that are dysfunctional in depression. Since anhedonia is a feature of depression and there is evidence of dysfunction of the reward system, DBS to the nucleus accumbens (NAcc) might be promising.
Methods
Ten patients suffering from very resistant forms of depression (treatment-resistant depression [TRD]), not responding to pharmacotherapy, psychotherapy, or ECT, were implanted with bilateral DBS electrodes in the NAcc. The mean (±SD) length of the current episode was 10.8 (±7.5) years; the number of past treatment courses was 20.8 (±8.4); and the mean Hamilton Depression Rating Scale (HDRS) was 32.5 (±5.3).
Results
Twelve months following initiation of DBS treatment, five patients reached 50% reduction of the HDRS (responders, HDRS = 15.4 [±2.8]). The number of hedonic activities increased significantly. Interestingly, ratings of anxiety (Hamilton Anxiety Scale) were reduced in the whole group but more pronounced in the responders. The [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography data revealed that NAcc-DBS decreased metabolism in the subgenual cingulate and in prefrontal regions including orbital prefrontal cortex. A volume of interest analysis comparing responders and nonresponders identified metabolic decreases in the amygdala.
Conclusions
We demonstrate antidepressant and antianhedonic effects of DBS to NAcc in patients suffering from TRD. In contrast to other DBS depression studies, there was also an antianxiety effect. These effects are correlated with localized metabolic changes.

Key Words: Deep brain stimulation; functional neuroimaging; major depression; neuromodulation; nucleus accumbens; treatment resistance

Deep Brain Stimulation: Beyond Movement Disorders

The 2010 Progress Report on Brain Research

By Brenda Patoine

Excellent review on DBS for psychiatric indications. Read it here.

US Study Of Deep Brain Stimulation For Obsessive-Compulsive Disorder?

Butler Hospital in Providence, R.I., is leading a clinical study evaluating the effectiveness and safety of deep brain stimulation (DBS) for severe obsessive-compulsive disorder (OCD). Benjamin D. Greenberg, MD, PhD, associate professor of psychiatry at Butler Hospital and the Alpert Medical School of Brown University, is the lead investigator. He noted, "In the most severe cases, OCD causes profound impairment in work and social life, as well as tremendous suffering. Our work, plus that of colleagues in Europe, shows that DBS is a promising treatment for patients with OCD who remain very ill and debilitated despite the best available standard treatments, which are cognitive behavioral therapy and medications."

In DBS, thin wires are implanted in brain circuits that are involved in OCD. The wires are connected under the skin to a battery-powered stimulating device, which is implanted in the patient's chest. These are the same kinds of devices that have become an FDA-approved standard of care for people with Parkinson's disease and other movement disorders. Pilot studies at Butler's OCD Research Clinic, Massachusetts General Hospital, and the other centers that are part of this trial have found that stimulation in this area reduced OCD symptoms.

According to the World Health Organization, OCD is one of the most disabling medical conditions. DBS offers people who have not been helped by specific behavior therapy for OCD and medications another potential treatment option.

The U.S. Food and Drug Administration has approved DBS for humanitarian use for patients with OCD. The study is working closely with other scientists and physicians who were just awarded funding by the National Institute of Mental Health to establish the Silvio O. Conte Center to carry out research to understand more about DBS in OCD. Suzanne Haber, PhD, heads this center at the University of Rochester Medical Center, and Dr. Greenberg at Butler Hospital and Brown University is its co-director.

Dr. Greenberg says that there is also a companion study of brain functioning in OCD that does not involve surgery.

Source: Butler Hospital

Using Deep Brain Stimulation on the Mind: Handle with Care

A great article by Mahlon R. DeLong on DBS in the DANA Foundation Magazine.

The abstract:

Deep brain stimulation has worked for many patients with Parkinson’s disease and other movement disorders that have not responded to other treatments. However, its use as a therapy for psychiatric disorders, while promising, is not yet proven. Mahlon DeLong, a pioneer in the use of deep brain stimulation, explains the technique and why its use for depression, obsessive-compulsive disorder and other psychiatric problems requires extra caution.

Deep Brain Stimulation for Severe Alcoholism

The Neurocritic Blog writes somewhat critically about data recently published on the use of DBS for the treatment of Alcoholism He cites a recent paper on ethical issues of dbs in psychiatry. Very interesting, read it here.