Mind Safari

ScienceDaily (Mar. 6, 2010) — Conventional antidepressant treatments generally require three to four weeks to become effective, thus the discovery of treatments with a more rapid onset is a major goal of biological psychiatry. The first drug found to produce rapid improvement in mood was the NMDA glutamate receptor antagonist, ketamine.

In a new issue of Biological Psychiatry, published by Elsevier, researchers from the National Institutes of Health report that another medication, scopolamine, also appears to produce replicable rapid improvement in mood. Scopolamine temporarily blocks the muscarinic cholinergic receptor, thought to be overactive in people suffering from depression.

Drs. Wayne Drevets and Maura Furey recruited outpatients with major depressive disorder who were randomly assigned to receive placebo and then scopolamine treatment, or vice versa, in a double-blinded design so that neither the researchers nor the patients knew which treatment they were receiving.

“Scopolamine was found to reduce symptoms of depression within three days of the first administration. In fact, participants reported that they experienced relief from their symptoms by the morning after the first administration of drug,” explained Dr. Furey. “Moreover, one-half of participants experienced full symptom remission by the end of the treatment period. Finally, participants remained well during a subsequent placebo period, indicating that the antidepressant effects persist for at least two weeks in the absence of further treatment.”

The efficacy of scopolamine is very interesting because the potent blockade of muscarinic receptors was a property of tricyclic antidepressant medications, the oldest type of antidepressants. With these medications, the muscarinic receptor blockade was mostly viewed as the cause of unwanted side effects, such as constipation, sedation, and memory impairments. Newer antidepressants, such as serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors, were explicitly designed to avoid blocking muscarinic receptors. Yet, the current data raise the possibility that this strategy may have increased safety and tolerability of these medications at the expense of providing effective and timely relief for depression symptoms.

Dr. John Krystal, Editor of Biological Psychiatry, commented that these findings “have the potential to raise expectations for new antidepressant treatments. Three-to-six weeks is a long time to wait for depression symptoms to be alleviated. Depressed people describe their emotional state using terms like ‘agony’ and others compare their condition to ‘living in hell’. Further, depression is a life-threatening condition for some, preventing them from performing basic self-care functions or causing them to exhibit self-destructive behavior.”

Although these findings open the door to a conceptually different approach to the treatment of depression, it remains to be seen whether rapid acting antidepressant effects will be viable clinically. One could imagine that they might mitigate hospitalization in some patients and enhance the overall effectiveness of the treatment of depression. However, this possibility remains to be demonstrated empirically in studies that show that a rapid-acting antidepressant treatment can be smoothly transitioned to definitive long-term treatment for depression.

Toyota is king of hybrids, with the iconic Prius and a long list of Toyota and Lexus models available with gas-electric drivetrains. General Motors thinks it has an ace up its sleeve with Extended-Range Electric Vehicles, like the Chevy Volt, that drive up to 40 miles on battery power and then start a gas engine.

But only Nissan, so far, has been willing to go all-in on electric cars. The company plans to offer the first mass-produced purely electric vehicle built by a major automaker (unless you count the six-figure boutique sports car made by Tesla) next year. The Nissan Leaf is a five-seat, small to midsize hatchback without any gasoline engine at all, just a battery pack and an electric motor.

Trying to sell an electric car to V8-loving America is a gamble. But the automotive press has finally had the chance to drive a prototype, and early reports say that Nissan may have built something remarkable.

The Los Angeles Times reports, “In the Leaf — an all-electric, five-passenger car that will start hitting American streets in late 2010 — you step on the accelerator and the car spools out velocity in one continuous, syrupy stream. It’s nothing short of elegant.” Under the control of the Times’ Dan Neil, a Leaf loaded down with the weight of four adults “shot across [a] stadium parking lot like it had been pinged with a BB gun.” The Times estimates that the Lead offers zero-to-40 mph acceleration “in the mid-5-second range, which would suit a decently sporty little car.”

And it’s butter-smooth acceleration. The Times explains, “Every year, automotive engineers find new ways to smooth more rough edges off the conventional automobile.” Computer-controlled automatic transmissions boasting as many as eight speeds, Continuously Variable Transmissions with no gears at all, and “suites of computer programming that modulate engine torque at the precise moments of gear change” have made the experience of driving most modern cars very smooth. But they can’t match the simple physics of an electric engine. The Leaf offers nearly 100 percent of its available torque at all times, creating a driving experience the Times calls “Sweet, glycerin smooth, techy, frisky and even a little bit beautiful.”

Autoblog had a little time behind the wheel as well. They report, “While the Leaf powertrain doesn’t accelerate like a Tesla Roadster, it’s got more than enough get-up-and-go for a standard family car, even with four adults on board. Considering the Leaf will cost something like a third or a fourth as much as a standard Roadster, we think the car will cause a fair share of EV grins once it’s unleashed into the wild.” They add, “After getting up to speed, we found the regenerative brakes felt great. While Nissan is still fine-tuning the system for production, they grip solidly whether you’re going fast or slow, gently applying pressure or hitting them hard.”

Nissan hasn’t announced final pricing on the Leaf, but analysts believe the car may cost under $25,000 when it arrives late next year.

It may also be the first of several electric vehicles from Nissan. The Wall Street Journal reports that Nissan CEO Carlos Ghosn recently “said in an interview the companies will launch four electric vehicles globally, with three of them coming to the U.S., including the Nissan Leaf compact, a light commercial vehicle suitable for use by companies such as FedEx, and eventually an electric car to be marketed under the Infiniti luxury brand.”

by John A. Speyrer

ScienceDaily (Jan. 11, 2010) — A team of neurosurgeons at Heidelberg University Hospital and psychiatrists at the Central Institute of Mental Health, Mannheim have for the first time successfully treated a patient suffering from severe depression by stimulating the habenula, a tiny nerve structure in the brain. The 64-year-old woman, who had suffered from depression since age 18, could not be helped by medication or electroconvulsive therapy. Since the procedure, she is for the first time in years free of symptoms.

Scientific studies have shown that the habenula is hyperactive in depression, the idea was to downregulate this structure by deep brain stimulation. The surgical procedure is based on a hypothesis of how the habenula is involved in depression that was first formulated by Dr. Alexander Sartorius, psychiatrist at the Central Institute for Mental Health (CIMH; Director: Professor Andreas Meyer-Lindenberg; former Director CIMH Professor Fritz Henn, Brookhaven National Laboratory, New York). The stereotactic procedure at the Neurosurgery Department of Heidelberg University Hospital (Medical Director: Professor Andreas Unterberg) was performed by Dr. Karl Kiening, head of stereotactic neurosurgery. The concept of habenula stimulation and the case study were published in the leading scientific journal Biological Psychiatry.

A new treatment option for therapy-resistent depression

Depression is a common psychiatric illness; some one third of patients do not respond to medication or psychotherapy. Electroconvulsive therapy, used for such severe or treatment resistant cases, is also not always effective. This was also the case for the Heidelberg/Mannheim patient, who never reached sustained remission after electroconvulsive therapy.

In deep brain stimulation, electrodes are inserted into the brain and are connected with wires under the skin to an electronic impulse generator implanted in the chest. The electrodes emit current that continuously stimulates specific areas of the brain. This therapy, also described as “brain pacemaker,” is already used successfully for patients suffering from Parkinson’s disease or other movement disorders.

Depressive patients have already been treated with electrostimulation with some success. However, two other areas of the brain were stimulated, located in the forebrain or midbrain regions. The habenula (Latin for the diminutive of reins) is located further downstream next to the brain stem. “We decided to stimulate the habenula because it is involved is the control of three major neurotransmitter systems, which are known to be disturbed in depression,’” explained psychiatrist Dr. Alexander Sartorius from the Central Institute of Mental Health.

The neurosurgical implantation of two electrodes demands utmost precision in planning and performance. The target area is about half as large as the others that are typically targeted for movement disorders, and in addition, is located in the middle of the brain, i.e. in the wall of what is known as the ‘third ventricle’. Implanting the electrodes in the two habenulae therefore requires the utmost precision that can currently be achieved with stereotactic instruments. “The neurosurgery department at Heidelberg University Hospital is optimally equipped for demanding procedures such as this with among other things, the new intraoperative highfield MRI,” says Dr. Kiening.

Multicenter study on habenula stimulation in preparation

The success of the procedure was confirmed when the electrode was accidentally switched off: the patient had a bicycle accident which required surgery for which an ECG had to be made as preparation. The brain pacemaker was switched off and was not reactivated for a few days, and the depression promptly returned. A few weeks after reactivation, the patient completely recovered again.

The neurosurgeons in Heidelberg and the psychiatrists in Mannheim now want to build on this positive experience and are planning a clinical study in which the habenula stimulation is to be implemented for severely depressive patients at five psychiatric-neurosurgery centers in Germany. “We aim to show that habenula stimulation has a better success rate than other target areas attempted for depression and that it is also safe to use,” says Dr. Sartorius, Coordinating Investigator of the proposed study.

Depression statistics:

-  Approximately 18.8 million American adults, or about 9.5 percent of the U.S. population age 18 and older in a given year, have a depressive disorder.

-  Nearly twice as many women (12.0 percent) as men (6.6 percent) are affected by a depressive disorder each year. These figures translate to 12.4 million women and 6.4 million men in the U.S.

-  Women between the ages of 25-44 are most often affected by depression with a major cause of depression in women being the inability to express or handle Anger.

-  Depression affects all people regardless of age, geographic location, demographic or social position.

-  Depressive disorders are appearing earlier in life with the average age of onset 50 years ago being 29 whereas recent statistics indicate it at just 14.5yrs in today’s society.

-  Depressive disorders often co-occur with anxiety disorders and substance abuse.

-  A recent study sponsored by the World Health Organization and the World Bank found unipolar major depression to be the leading cause of disability in the United States.

House-flipper Chris Prelitz greenovates a 1600 sq. ft. house in Laguna Woods California.