Archive for the ‘Neuropsychopharmacology’ Category

Nearly 150 years ago, Charles Darwin recognized that facial expressions not only communicate the emotions we feel but intensify them, by sending cues back to the brain. In the ensuing decades, researchers proved again and again that we can influence the way we feel by the visage we project. Smiling can help us feel happier. Frowning can make us feel angrier.

But it was only in the past few years that a dermatologist from Chevy Chase, Md., noticed that some of the patients whose brows he temporarily paralyzed with Botox, to remove wrinkles, began to feel relief from depression. That physician, Eric Finzi, took his idea to psychiatrist, Norman Rosenthal, who teaches at Georgetown Medical School and had spent many years studying how light and odors, transmitted to the brain through the nerves that connect it with the eyes and nose, affect our moods.

Now there have been three small studies that show that Botox injections can help with depression. In the latest, published in the current issue of the Journal of Psychiatric Research, Finzi and Rosenthal showed that 17 of 33 patients experienced better than 50 percent reductions in their depression symptoms after a single Botox injection, and 27 percent of the group saw their depression go into remission. The study confirms a similar one reported in 2012 by German researchers Tillmann Kroger and Axel Wollmer, who spoke of their findings at a meeting of the American Psychiatric Association in New York this past weekend.

“There are several nerves, about 12 of them, that go straight into the brain through the skull,” Rosenthal told me Tuesday. “…We’re used to thinking of them in terms of their outbound messages or signals. We’re not used to thinking of them in terms of their inbound messages.”

The idea holds promise as a supplement or alternative to anti-depressants and psychotherapy for treating depression, according to Rosenthal. Minuscule amounts of Botox — which is made from the lethal botulinum toxin — are injected into the facial muscles and don’t even enter the bloodstream. The procedure has shown no side-effects.

If the whole idea seems almost too outlandish to believe — as it did for me — Rosenthal was quick to point out that he was laughed at 30 years ago, when he proposed the idea of “seasonal affective disorder” and the notion that exposing people to bright light in the depths of winter could help with that kind of depression. “Now, it’s ubiquitous,” he said. “Then, they thought it was ridiculous.”

The treatment isn’t perfect. Botox is expensive, at about $400 per dose, wears off in about three months and isn’t covered by insurance. And as the studies showed, it doesn’t work for everyone.

But the botulinum toxin already is used to treat a wide variety of medical conditions. Perhaps depression is next.

http://www.washingtonpost.com/news/to-your-health/wp/2014/05/07/using-botox-to-treat-depression-seriously/

Doctors in the US have induced feelings of intense determination in two men by stimulating a part of their brains with gentle electric currents.

The men were having a routine procedure to locate regions in their brains that caused epileptic seizures when they felt their heart rates rise, a sense of foreboding, and an overwhelming desire to persevere against a looming hardship.

The remarkable findings could help researchers develop treatments for depression and other disorders where people are debilitated by a lack of motivation.

One patient said the feeling was like driving a car into a raging storm. When his brain was stimulated, he sensed a shaking in his chest and a surge in his pulse. In six trials, he felt the same sensations time and again.

Comparing the feelings to a frantic drive towards a storm, the patient said: “You’re only halfway there and you have no other way to turn around and go back, you have to keep going forward.”

When asked by doctors to elaborate on whether the feeling was good or bad, he said: “It was more of a positive thing, like push harder, push harder, push harder to try and get through this.”

A second patient had similar feelings when his brain was stimulated in the same region, called the anterior midcingulate cortex (aMCC). He felt worried that something terrible was about to happen, but knew he had to fight and not give up, according to a case study in the journal Neuron.

Both men were having an exploratory procedure to find the focal point in their brains that caused them to suffer epileptic fits. In the procedure, doctors sink fine electrodes deep into different parts of the brain and stimulate them with tiny electrical currents until the patient senses the “aura” that precedes a seizure. Often, seizures can be treated by removing tissue from this part of the brain.

“In the very first patient this was something very unexpected, and we didn’t report it,” said Josef Parvizi at Stanford University in California. But then I was doing functional mapping on the second patient and he suddenly experienced a very similar thing.”

“Its extraordinary that two individuals with very different past experiences respond in a similar way to one or two seconds of very low intensity electricity delivered to the same area of their brain. These patients are normal individuals, they have their IQ, they have their jobs. We are not reporting these findings in sick brains,” Parvizi said.

The men were stimulated with between two and eight milliamps of electrical current, but in tests the doctors administered sham stimulation too. In the sham tests, they told the patients they were about to stimulate the brain, but had switched off the electical supply. In these cases, the men reported no changes to their feelings. The sensation was only induced in a small area of the brain, and vanished when doctors implanted electrodes just five millimetres away.

Parvizi said a crucial follow-up experiment will be to test whether stimulation of the brain region really makes people more determined, or simply creates the sensation of perseverance. If future studies replicate the findings, stimulation of the brain region – perhaps without the need for brain-penetrating electrodes – could be used to help people with severe depression.

The anterior midcingulate cortex seems to be important in helping us select responses and make decisions in light of the feedback we get. Brent Vogt, a neurobiologist at Boston University, said patients with chronic pain and obsessive-compulsive disorder have already been treated by destroying part of the aMCC. “Why not stimulate it? If this would enhance relieving depression, for example, let’s go,” he said.

http://www.theguardian.com/science/2013/dec/05/determination-electrical-brain-stimulation

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.

benzotropine

A drug that treats Parkinson’s disease might also work against multiple sclerosis, or MS.

In MS patients, an aberrant immune onslaught degrades the fatty myelin sheaths that coat nerve fibers, causing blurred vision, weakness, loss of coordination and other symptoms.

Luke Lairson of the Scripps Research Institute in La Jolla, Calif., and colleagues tested a host of compounds to see which might boost regeneration of oligodendrocytes, the brain cells that make myelin and which are often lacking in MS. Using the cells’ forerunners, nascent brain cells called oligodendrocyte precursor cells, from rats and mice, the researchers found that benztropine proved adept at steering these cells to become myelin-making oligodendrocytes.

The researchers then induced in mice a disease that mimics MS and gave some of the animals benztropine, others a standard MS drug (fingolimod or interferon beta) and some no drug at all. Whether given before or after disease onset, benztropine reduced symptom severity and prevented relapses better than other MS drugs. Mice getting no drug fared the poorest, according to results appearing October 9 in Nature.

A cell count of brain tissue revealed that mice getting benztropine had substantially more mature oligodendrocytes than mice getting no drug. Further analyses suggested the animals’ symptom improvement with benztropine resulted from a rebuilding of the myelin sheaths, not from suppressing the animals’ immune systems. The researchers think the drug, if approved for use in MS, might work in concert with immune-suppressing drugs.

https://www.sciencenews.org/article/old-drug-may-have-new-trick

cocaine

Researchers at Weill Cornell Medical College have successfully tested their novel anti-cocaine vaccine in primates, bringing them closer to launching human clinical trials. Their study, published online by the journal Neuropsychopharmacology, used a radiological technique to demonstrate that the anti-cocaine vaccine prevented the drug from reaching the brain and producing a dopamine-induced high.

“The vaccine eats up the cocaine in the blood like a little Pac-man before it can reach the brain,” says the study’s lead investigator, Dr. Ronald G. Crystal, chairman of the Department of Genetic Medicine at Weill Cornell Medical College. “We believe this strategy is a win-win for those individuals, among the estimated 1.4 million cocaine users in the United States, who are committed to breaking their addiction to the drug,” he says. “Even if a person who receives the anti-cocaine vaccine falls off the wagon, cocaine will have no effect.”

Dr. Crystal says he expects to begin human testing of the anti-cocaine vaccine within a year.

Cocaine, a tiny molecule drug, works to produce feelings of pleasure because it blocks the recycling of dopamine — the so-called “pleasure” neurotransmitter — in two areas of the brain, the putamen in the forebrain and the caudate nucleus in the brain’s center. When dopamine accumulates at the nerve endings, “you get this massive flooding of dopamine and that is the feel good part of the cocaine high,” says Dr. Crystal.

The novel vaccine Dr. Crystal and his colleagues developed combines bits of the common cold virus with a particle that mimics the structure of cocaine. When the vaccine is injected into an animal, its body “sees” the cold virus and mounts an immune response against both the virus and the cocaine impersonator that is hooked to it. “The immune system learns to see cocaine as an intruder,” says Dr. Crystal. “Once immune cells are educated to regard cocaine as the enemy, it produces antibodies, from that moment on, against cocaine the moment the drug enters the body.”

In their first study in animals, the researchers injected billions of their viral concoction into laboratory mice, and found a strong immune response was generated against the vaccine. Also, when the scientists extracted the antibodies produced by the mice and put them in test tubes, it gobbled up cocaine. They also saw that mice that received both the vaccine and cocaine were much less hyperactive than untreated mice given cocaine.

In this study, the researchers sought to precisely define how effective the anti-cocaine vaccine is in non-human primates, who are closer in biology to humans than mice. They developed a tool to measure how much cocaine attached to the dopamine transporter, which picks up dopamine in the synapse between neurons and brings it out to be recycled. If cocaine is in the brain, it binds on to the transporter, effectively blocking the transporter from ferrying dopamine out of the synapse, keeping the neurotransmitter active to produce a drug high.

In the study, the researchers attached a short-lived isotope tracer to the dopamine transporter. The activity of the tracer could be seen using positron emission tomography (PET). The tool measured how much of the tracer attached to the dopamine receptor in the presence or absence of cocaine.

The PET studies showed no difference in the binding of the tracer to the dopamine transporter in vaccinated compared to unvaccinated animals if these two groups were not given cocaine. But when cocaine was given to the primates, there was a significant drop in activity of the tracer in non-vaccinated animals. That meant that without the vaccine, cocaine displaced the tracer in binding to the dopamine receptor.

Previous research had shown in humans that at least 47 percent of the dopamine transporter had to be occupied by cocaine in order to produce a drug high. The researchers found, in vaccinated primates, that cocaine occupancy of the dopamine receptor was reduced to levels of less than 20 percent.

“This is a direct demonstration in a large animal, using nuclear medicine technology, that we can reduce the amount of cocaine that reaches the brain sufficiently so that it is below the threshold by which you get the high,” says Dr. Crystal.

When the vaccine is studied in humans, the non-toxic dopamine transporter tracer can be used to help study its effectiveness as well, he adds.

The researchers do not know how often the vaccine needs to be administered in humans to maintain its anti-cocaine effect. One vaccine lasted 13 weeks in mice and seven weeks in non-human primates.

“An anti-cocaine vaccination will require booster shots in humans, but we don’t know yet how often these booster shots will be needed,” says Dr. Crystal. “I believe that for those people who desperately want to break their addiction, a series of vaccinations will help.”

Co-authors of the study include Dr. Anat Maoz, Dr. Martin J. Hicks, Dr. Shankar Vallabhajosula, Michael Synan, Dr. Paresh J. Kothari, Dr. Jonathan P. Dyke, Dr. Douglas J. Ballon, Dr. Stephen M. Kaminsky, Dr. Bishnu P. De and Dr. Jonathan B. Rosenberg from Weill Cornell Medical College; Dr. Diana Martinez from Columbia University; and Dr. George F. Koob and Dr. Kim D. Janda from The Scripps Research Institute.

The study was funded by grants from the National Institute on Drug Abuse (NIDA).

Thanks to Kebmodee and Dr. Rajadhyaksha for bringing this to the attention of the It’s Interesting community.