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Obesity Linked To Obsessive-Compulsive Behavior Via Brain Circuit

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Main Category: Obesity / Weight Loss / Fitness
Also Included In: Neurology / Neuroscience;  Psychology / Psychiatry
Article Date: 11 Jun 2013 – 3:00 PDT

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An investigation of the brain circuits behind compulsive behavior has surprisingly revealed they may be intimately linked
to circuits that control obesity. The US researchers say the discovery offers new insights into the development and treatment of
both compulsive behavior and eating disorders.

Study leaders and neuro-psychiatrists Michael Lutter and Andrew Pieper of the University of Iowa (UI), and colleagues, write
about their work in this week’s online early edition of the Proceedings of the National Academy of Sciences (PNAS)
.

They describe how they bred mice missing a gene known to cause obesity, and suspected of being involved in compulsive behavior, and mated them with mice bred to have compulsive
grooming and were surprised to see offspring that were neither obese nor compulsive groomers.

They say this shows the brain circuits that control obsessive-compulsive behavior are meshed with circuits that control food intake
and body weight: a finding that will have implications for treating the compulsive behavior in many psychiatric
diseases like obsessive-compulsive disorder (OCD), Tourette syndrome, and eating disorders.

Obese Mice and Compulsive Groomers

The researchers worked with two types of mice engineered for studying human disorders: one bred to study compulsive behavior
(Pieper’s field of interest), and the other bred to study an inherited form of obesity (Lutter’s specialism).

The compulsive behavior mice are missing a brain protein called SAPAP3, the lack of which causes them to groom themselves
excessively. The behavior can be effectively controlled with fluoxetine, a drug commonly used to treat OCD in people.

The inherited obesity mice lack a brain protein called MC4R. Mutations in the MC4R gene are the biggest single-gene cause of
over-eating and morbid obesity in people.

Lutter, an assistant professor of psychiatry at the UI Carver College of Medicine, is interested in MC4R signaling pathways and
how they affect the development of obesity.

“I’m also interested in how these same molecules affect mood and anxiety and reward, because it’s known that there is a
connection between depression and anxiety and development of obesity,” he explains in a statement.

What Happened When the Two Strains Interbred

Lutter and Pieper, who is an associate professor of psychiatry and neurology at Carver, were aware of an old study that suggested
MC4R might play a role not only in food intake and obesity, but also in compulsive behavior, so they decided to test the idea, as
Lutter explains:

“We knew in one mouse you could stimulate excessive grooming through this MC4R pathway and in another mouse a different
pathway (SAPAP3) caused compulsive grooming.”

“So, we decided to breed the two mice together to see if it would have an effect on compulsive grooming,” he adds.

The breeding experiment bore out their hypothesis: knocking out the MC4R protein in OCD mice lacking SAPAP3 normalized their
grooming behavior. And they also found chemically blocking the protein had the same effect, which was mirrored by normal
patterns in brain cell communication linked to compulsive behavior.

Unexpected Finding: Deleting Both SAPAP3 and MC4R Led to Normal Weight Mice

But they were surprised by another totally unexpected finding. Deleting SAPAP3, lack of which causes compulsive grooming,
restored normal weight in mice without MC4R, lack of which would normally make them obese.

“We had this other, completely shocking finding — we completely rescued body weight and food intake in the double null mouse,”
Lutter exclaims.

Thus it appeared that they were influencing two, until now unknown to be related, brain regions simultaneously: one involved in
grooming and behavior, the other with food intake and body mass.

Explanation May Lie In Evolution

Lutter suggests that while a connection between obesity and obsessive-compulsive behavior might not be obvious at first, there
could be an evolutionary explanation. Survival depends on eating clean, safe food, so when this is abundant, the drive increases,
and when it is scarce, it decreases.

“Obsessive behavior, or fear of contamination, may be an evolutionary protection against eating rotten food,” he
explains.

Oils and fats are calorie- and nutrient-rich but also spoil more quickly than foods that are less dense in nutrients and calories like
onions, apples and potatoes.

(Refrigeration, which reduces risk of contamination, has not been around long enough to have made an impact on the evolution of
these brain circuits.)

Lutter wonders if the circuits they have found help determine whether or not to eat calorie-dense foods.

Perhaps a disturbance in the circuits may on the one hand result in obesity because people are less anxious and obsessive and
consume energy-dense foods, and on the other hand they are excessively anxious and obsessive and limit their food selection or
intake, leading to disorders like anorexia nervosa, Tourette syndrome, or OCD.

Pieper says they now want to find out if the two pathways talk to each other. Whatever the answer, it is likely to increase
understanding toward new drugs for treating some of these disorders.

Funds from The Hartwell Foundation, the Brain and Behavior Foundation, the National Institutes of Health and a NARSAD
Young Investigator Award helped finance the study.

In another study published in January 2013, researchers at MIT describe how they used optogenetic brain stimulation to block compulsive behavior
in mice lacking SAPAP3.

Written by Catharine Paddock PhD

Copyright: Medical News Today

Not to be reproduced without permission of Medical News Today

  • Additional
  • References
  • Citations

“Double deletion of melanocortin 4 receptors and SAPAP3 corrects compulsive behavior and obesity in mice”;

Pin Xu, Brad A. Grueter, Jeremiah K. Britt, Latisha McDaniel, Paula J. Huntington, Rachel Hodge, Stephanie Tran, Brittany L.

Mason, Charlotte Lee, Linh Vong, Bradford B. Lowell, Robert C. Malenka, Michael Lutter, and Andrew A. Pieper; PNAS,

published online ahead of print 10 June 2013; DOI: 10.1073/pnas.1308195110; Link to Abstract.

Additional source: Iowa Now from The University of Iowa.

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Obsessive-Compulsive And Obesity Genes Could Be Related

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The study, led by neuropsychiatrists Michael Lutter and Andrew Pieper from the University of Iowa, examined the effects of breeding two genetically altered mice. One of the mice lacked a gene called SAPAP3, which caused it to groom itself to the point that it had lesions in its skin, while the other mouse lacked a gene called MC4R, causing it to be obese. Deficiencies in MC4R are the most common single-gene cause of morbid obesity and over-eating in people. The gene is also suspected to play a part in compulsive behavior.

Based on previous studies, the team knew that obesity gene MC4R was related to compulsiveness in some sort of way. Their original intent was to see the effects breeding would have on compulsiveness.

“We knew in one mouse you could stimulate excessive grooming through this MC4R pathway, and in another mouse a different pathway (SAPAP3) caused compulsive grooming,” Lutter said. “So, we decided to breed the two mice together to see if it would have an effect on compulsive grooming.”

Their hypothesis was correct. The mice born to the two genetically altered mice had neither MC4R nor SAPAP3, and their grooming behavior was normal. This meant that the compulsiveness associated with a lack of SAPAP3 was balanced out by the lack of MC4R, which can cause compulsiveness when present — their brain cell communication patterns linked to compulsive behavior were normalized.

But going further than normalized grooming, the researchers also found that the mice didn’t grow to become obese. Although the mice had no MC4R, which could have caused them to become obese, the lack of SAPAP3 took away their compulsive behavior.

“We had this other, completely shocking finding — we completely rescued body weight and food intake in the double null mouse,” Lutter said. “So, not only were we affecting the brain regions involved in grooming and behavior, but we also affected the brain regions involved in food intake and body weight.”

Compulsive behavior has been associated with many forms of psychiatric disease, most notably obsessive-compulsive disorder (OCD), but also Tourette syndrome, and eating disorders.

When speaking about his specialty, MC4R, Lutter said, “I’m also interested in how these same molecules affect mood and anxiety and reward, because it’s known that there is a connection between anxiety and development of obesity.”

According to a 2006 National Institute of Mental Health-funded study, one out of four cases of obesity is associated with a mood or anxiety disorder. However, the causal relationship between the two remains undetermined. The study found that the increasing rates of obesity in the U.S. are in-line with the increasing rates of depression, bipolar disorder, panic disorder, and many other disorders. It also found that social and cultural factors seem to influence the presence of obesity, with the strongest connection among college-educated non-Hispanic whites ages 29 and younger.

However, Lutter believes that the connection between compulsive behavior and obesity lies in the evolutionary need to eat safe, clean food.

“Food safety has been an issue through the entire course of human evolution — refrigeration is a relatively recent invention,” he said. “Obsessive behavior, or fear of contamination, may be an evolutionary protection against eating rotten food.”

Sources: Lutter M, Pieper A, Xu P, et al. Double deletion of melanocortin 4 receptors and SAPAP3 corrects compulsive behavior and obesity in mice. PNAS. 2013.

Simon GE, Korff M, Saunders K, et al. Association Between Obesity and Psychiatric Disorders in the U.S. Adult Population. Archives of General Psychiatry. 2006

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10 signs you may have obsessive-compulsive disorder

Hooked on hand sanitizer? Closet organized to a T? Quirks like this can usually be chalked up to personality or preference, but in some cases they may point to a more serious issue: obsessive-compulsive disorder (OCD), a condition marked by obsessive thoughts and compulsions that affects about 1 percent of U.S. adults.

How can you tell if OCD tendencies are symptoms that require professional help? There’s no easy test, as it’s usually a matter of degree, said Jeff Szymanski, executive director of the International OCD Foundation, a Boston-based advocacy organization. Still, there are certain patterns that may indicate the full-blown disorder. Here are 10 of the most common.

Hand-washing

Compulsive hand-washing or hand sanitizer use is so prevalent in OCD that “washers” has become a widely accepted category of OCD patient. The urge commonly stems from a fear of germs (the most common obsession seen in OCD), but it also can be rooted in fears of making others sick or of being impure or immoral.

When to seek help: If you think about germs even after washing your hands, worry that you’re not scrubbing well enough, or have irrational fears about disease (such as getting HIV from a shopping cart), it could be a sign that your hand-washing is compulsive, Szymanski said. Elaborate hand-washing routines—needing to wash five times and get soap under each nail, for example—are another warning sign.

Health.com: Do You Have an Anxiety Disorder?

Overzealous cleaning

People with OCD who fall into the “washers” category also tend to clean compulsively. As with hand-washing, housecleaning is often a way of easing germaphobia or feelings of impurity. Although cleaning can help chase these obsessive thoughts away, the relief does not last, and the urge to clean is often even stronger the next time.

When to seek help: If you spend hours a day cleaning, it’s almost certainly related to OCD, but it’s harder to know if cleaning for an hour a day could be a sign of OCD. “It’s really the consequence of stopping,” said Dr. Michael Jenike, a psychiatrist at Massachusetts General Hospital, in Boston. “If you don’t [clean], you get terribly anxious and fearful.”

Checking behavior

So-called checking behaviors—returning three, four, or even 20 times to make sure the oven is off or the front door is locked—are the most common compulsions associated with OCD, affecting nearly 30 percent of people with the disorder. Like other compulsive behaviors, checking can be driven by a variety of obsessions, ranging from a fear of getting hurt to deep-seated feelings of irresponsibility.

When to seek help: It’s normal to double-check something once in a while. But if checking interferes with your daily life (by making you late for work, say), or becomes a ritual that you can’t do without, it could be a sign of OCD. Jenike has patients who are compelled to check the oven exactly three times, for instance.

Health.com: 12 Ways We Sabotage Our Mental Health

Counting

Some people with OCD perform tasks according to a certain numeric pattern or count to themselves as they do everyday things (such as climbing stairs or cleaning). These behaviors may be driven by superstitions. For instance, a belief that the number seven is good may lead someone to feel that they’ll hurt themselves or someone else if they don’t take seven steps at a time.

When to seek help: “It’s all about context—does the behavior make sense in your life?” Szymanski says. Counting can be a good distraction as you walk to your car or climb the stairs to your office. “If it doesn’t bother you or anybody else, you are fine,” Jenike said. “People come to me if they can’t get numbers out of their head.”

Organization

People with OCD can take organizing to the level of perfectionism. “It has to feel just right, look just right, be symmetrical, be the right number [of items],” Szymanski says. This fussiness is often driven by obsessions about order and symmetry.

When to seek help: “I’m neat and organized and like things a certain way, but it is out of preference,” said Szymanski, author of The Perfectionist’s Handbook. OCD enters in when want to becomes have to: People like Szymanski enjoy a tidy desk and find it helpful, whereas people with OCD may not necessarily want to organize their desk but feel they must, in order to relieve their anxiety.

Health.com: Natural Remedies for Anxiety

Fears of violence

Everybody has fleeting thoughts about the possibility of being affected by violence or other misfortunes. The more we try to avoid thoughts like this, the more they pop into our heads, research shows—and this appears to be especially true for people with OCD. They “could be trying harder to suppress these thoughts,” Szymanski said, “or they may react more intensely to them because they deem them as unacceptable.”

When to seek help: It’s important to recognize that we all have occasional dark thoughts, Szymanski said. But it could be a sign of OCD if thoughts of getting mugged make you avoid the park, for example, or if concern for your mother’s safety spurs you to call her several times a day.

Unwanted sexual thoughts

Just like violent thoughts, recurring unwanted thoughts about inappropriate or taboo sexual behavior frequently occur in OCD. Patients may imagine for an instant that they are going to grope their coworker or molest a child, or wonder if they are gay instead of straight (or vice versa).

When to seek help: “Most people can say, ‘Oh, I don’t really want to do that or it doesn’t represent who I am as a person,'” Szymanski said. “But someone with OCD thinks, ‘These thoughts are terrible, no one else has them, what do they mean about me.'” Changing your behavior as a result of these thoughts—avoiding gay friends or a coworker you’ve thought about sexually, for instance—is another red flag.

Health.com: 10 Subtle Signs of Bipolar Disorder

Dwelling on relationships

People with OCD are known to obsessively dissect their relationships with friends, coworkers, romantic partners, and family members. For example, they may dwell at length on whether an offhand comment at work alienated a coworker, or whether a small misunderstanding ruined a romantic relationship. This mind-set may reflect an exaggerated sense of responsibility and difficulty accepting uncertainty.

When to seek help: “Breaking up with a girlfriend or boyfriend can make anyone ‘obsess,’ whether or not they have OCD,” Jenike said. But it may be a sign of OCD if thoughts like this get stuck in your head and snowball into excessive self-doubt or fears of being a bad person.

Seeking reassurance

One way people with OCD try to soothe their anxiety is by asking for the opinion of their friends and family. If they’re concerned they embarrassed themselves at a party, for instance, they may repeatedly ask a friend to replay the incident. Asking friends to weigh in (“Does my house seem dirty to you?”) can also be a strategy for avoiding compulsive behaviors.

When to seek help: Everyone uses their friends as a sounding board, but if you catch yourself repeating the same question over and over—or if your friend points this out—it could signal OCD. What’s more, the reassurance you get from loved ones could be enabling your obsessiveness.

Health.com: 12 Signs of Depression in Men

Hating your looks

Body dysmorphic disorder (BDD) is a condition related to OCD in which people fixate on a part of their body they consider abnormal or unattractive—often their nose, skin, or hair. (Unlike eating disorders, BDD doesn’t involve a focus on weight or diet changes.) The obsessive thoughts associated with BDD are very similar to those seen in OCD. Many people with BDD also have OCD and worry about the cleanliness of their body in addition to how it looks.

When to seek help: It’s normal to dislike some aspects of your features. But people with BDD may spend hours a day checking the mirror. “You overvalue how important it is to you and others and may avoid being around people,” Szymanski said.

This article originally appeared on Health.com

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Brain Circuits Link Obsessive-Compulsive Behavior and Obesity

The University of Iowa-led researchers bred mice missing a gene known to cause obesity, and suspected to also be involved in compulsive behavior, with a genetic mouse model of compulsive grooming. The unexpected result was offspring that were neither compulsive groomers nor obese.

The study, published the week of June 10 in the online early edition of the Proceedings of the National Academy of Sciences (PNAS), suggests that the brain circuits that control obsessive-compulsive behavior are intertwined with circuits that control food intake and body weight. The findings have implications for treating compulsive behavior, which is associated with many forms of psychiatric disease, including obsessive-compulsive disorder (OCD), Tourette syndrome, and eating disorders.

UI neuro-psychiatrists Michael Lutter, M.D., Ph.D. and Andrew Pieper, M.D., Ph.D., led the study. The team also included researchers from Stanford University School of Medicine, University of Texas Southwestern Medical Center, Beth Israel Deaconess Medical Center, and Harvard Medical School.

Lutter, an assistant professor of psychiatry, and Pieper, an associate professor of psychiatry and neurology at the UI Carver College of Medicine, both recently arrived at the UI and use mouse models in their laboratories to study human disorders and conditions.

Pieper is interested in compulsive behavior. His mouse model of compulsivity lacks a brain protein called SAPAP3. These mice groom themselves excessively to the point of lesioning their skin, and their compulsive behavior can be effectively treated by fluoxetine, a drug that is commonly used to treat OCD in people.

Lutter works with a mouse that genetically mimics an inherited form of human obesity. This mouse lacks a brain protein known a MC4R. Mutations in the MC4R gene are the most common single-gene cause of morbid obesity and over-eating in people.

“I study MC4R signaling pathways and their involvement in the development of obesity,” Lutter explains. “I’m also interested in how these same molecules affect mood and anxiety and reward, because it’s known that there is a connection between depression and anxiety and development of obesity.”

An old study hinted that in addition to its role in food intake and obesity, MC4R might also play a role in compulsive behavior, which got Lutter and Pieper thinking of ways to test the possible interaction.

“We knew in one mouse you could stimulate excessive grooming through this MC4R pathway and in another mouse a different pathway (SAPAP3) caused compulsive grooming,” Lutter says. “So, we decided to breed the two mice together to see if it would have an effect on compulsive grooming.”

The experiment proved their original hypothesis — knocking out the MC4R protein in the OCD mouse normalized grooming behavior in the animals. In addition, chemically blocking MC4R in the OCD mice also eliminated compulsive grooming. The rescued behavior is mirrored by normalization of a particular pattern of brain cell communication linked to compulsive behavior.

However, the breeding experiment revealed another totally unexpected result. Loss of the SAPAP3 protein from the mice that were obese due to lack of MC4R produced mice of normal weight.

“We had this other, completely shocking finding — we completely rescued body weight and food intake in the double null mouse,” Lutter says. “So, not only were we affecting the brain regions involved in grooming and behavior, but we also affected the brain regions involved in food intake and body weight.”

Although obesity and obsessive-compulsive behavior may seem unrelated, Lutter suggests that the connection may be rooted in the evolutionary need to eat safe, clean food in times of a food abundance, and to lessen this drive when food is scarce.

“Food safety has been an issue through the entire course of human evolution – refrigeration is a relatively recent invention,” he says. “Obsessive behavior, or fear of contamination, may be an evolutionary protection against eating rotten food.”

Oils and fats have lots of calories and nutrients but they also spoil much more easily than less nutrient- and calorie-dense foods like potatoes, onions, or apples.

“I think this circuit that we have uncovered is probably involved in determining whether or not people should eat calorically dense foods,” he says.

Lutter suggests that slight perturbations in this system might lead, on one hand, to disorders that link anxiety and obsessive behavior to limited food selection or intake, such as anorexia nervosa, Tourette syndrome, or OCD, and on the other hand, to obesity, where people over-consume high-fat foods and may have decreased obsessive behavior and anxiety.

“The next step will be to determine how these two pathways communicate with one another, in hopes of identifying new ways to develop drugs to treat either of these disorders,” says Pieper.

The research was funded by grants from The Hartwell Foundation, the Brain and Behavior Foundation, and the National Institutes of Health (DK081185-01, DK081182-01, MH084058-01A1, RO1DK075632, P30DK046200, P30DK057521, F3DK078478). Lutter also was funded by a NARSAD Young Investigator Award.

Anxiety disorder colors makeup artist’s creations

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Chester Higgins Jr. | The New York Times

David Klasfeld, founder of Obsessive Compulsive Cosmetics, in his New York shop

By 

Laren Stover

NEW YORK TIMES NEWS SERVICE

Sunday June 9, 2013 5:15 AM

NEW YORK — “Venus’ flytraps are sort of my spirit animal,” David Klasfeld said, referring to the
lusty pink-and-green plant tattoos curling around his bicep.

“There’s a line from
Little Shop of Horrors: ‘They say the meek shall inherit,’ and for some reason people are
always telling me how humble I am. But I do know what I’m doing, and if anything I’m trying to be
aggressive.”

Klasfeld — who is as slight and sinewy as the sleepwalker Cesare (tattooed on his shoulder) from
the 1920 film
The Cabinet of Dr. Caligari — is a makeup artist and the CEO, creative director and
founder of Obsessive Compulsive Cosmetics.

It is best-known for Lip Tar, a cult favorite among cutting-edge makeup enthusiasts. The company
is named after Klasfeld’s obsessive-compulsive disorder, diagnosed when he was 14.

“I had 42 shampoos and conditioners because I could never use the same ones twice in a week, so
I could go six weeks without using the same combination,” said Klasfeld, now 35. “I didn’t name the
company arbitrarily.”

The line also has the distinction of being completely vegan and “cruelty-free.” People for the
Ethical Treatment of Animals honored the line with a trailblazer award, which is framed on the wall
of Klasfeld’s store and headquarters.

He was sitting there recently in a cramped back space, while a team of five worked on computers
and mixed nocturnal shades of scarlet in paper cups. He frequently invites this crew to his
apartment to watch movies for inspiration.
Blade Runner and
Prometheus were significant influences for a Sci-Fi Lullabies collection, released this
spring, he said.

Growing up in Fort Lee, N.J., Klasfeld became consumed by cosmetics at a young age.

“One of my earliest memories was being at a friend’s sixth birthday party, and she got a Barbie
head — the kind you could paint the makeup on — and as soon as she unwrapped it, I grabbed it and
locked myself in the bathroom with it because I wanted it so badly,” he said.

In high school, he quietly pored over
Allure magazine in the back of the cafeteria and became the head of the theater makeup
department.

He went on to major in film at the State University of New York at Purchase, taking a job as a
color consultant at the Body Shop, a pioneer in the cruelty-free cosmetics market. In 2004,
Klasfeld struck out on his own, mixing two vegan lip balms in his kitchen — naming one Tarred and
one Feathered — and selling them online and at makeup stores.

The company now has almost 300 products, including concealers and nail lacquers, which are sold
at 240 North American Sephora stores.

Humane animal treatment may be the brand’s mission statement, but counting rituals play a role
in the brand’s strategy. “

What’s been amazing about the company is turning what’s viewed as a negative into a positive,”
said Klasfeld of obsessive-compulsive disorder. “Coordinating and matched sets are definitely
things that are born out of an OCD mind.”

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Surgery for obsessive compulsive disorder sufferers is safe and effective

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Around half of patients with extreme OCD respond well to psychosurgery treatment

Around half of people with an extreme form of obsessive compulsive disorder responded well to a type of psychosurgery that proved to be safe and effective, according to research published online in the Journal of Neurology, Neurosurgery, Psychiatry.

Researchers from Canada have now recommended physicians should consider this approach in helping people with OCD who have not responded to any other type of treatment.

Obsessive compulsive disorder (OCD) is a psychiatric disease which leads to anxiety-provoking thoughts (obsessions) causing repeated, time-consuming behaviors (compulsions) that might or might not provide temporary relief. Around 1 to 2% of the population is thought to have OCD that is severe enough to disrupt their life.

Standard treatments for the disorder are antidepressant medication and/or psychotherapeutic help such as cognitive behavioural therapy, but other studies have shown that such treatment does not help relieve symptoms for between 20-30% of patients.

Psychosurgery for OCD is sometimes carried out, but is rare and few studies have examined the benefits of this surgery.

Researchers from the Department of Neurological Sciences at Universit Laval, Quebec, therefore, decided they would study the efficacy and possible complications of one type of such surgery bilateral anterior capsulotomy in patients with severe OCD who had not responded to any other treatments over a long time period.

Nineteen patients were studied who had a severe form of OCD that had not responded to drugs or psychotherapeutic treatment. All of these patients underwent psychosurgery in the form of bilateral capsulotomy between 1997 and 2009.

They were evaluated before the surgery and then periodically afterwards for two years as well as being contacted again at an average of seven years after their operation to check on their progress.

Using a tool called the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the researchers measured the patients’ symptom severity. A patient with an improvement rate of over 35% in the Y-BOCS score was considered a responder, while a patient with a 25% improvement was considered a partial responder.

Their results showed that 36.8% of the patients responded fully to the procedure and 10.5% were considered partial responders, meaning that almost half of the patients (47.3%) responded to the surgery.

At the end of the study, three out of the 19 patients had recovered from their OCD, three were in remission (meaning their symptoms were reduced to a minimum level) and no deaths were reported. Only two patients had permanent surgical complications.

They concluded: “We are aware of the many ethical and sociopolitical considerations related to psychosurgery, but we think that such surgery is appropriate under thoughtful regulation, particularly when the disorder is chronic, intractable to non-invasive treatment modalities and when surgery is the last therapeutic option.”

[Bilateralstereotactic anterior capsulotomy for obsessive-compulsive disorder: long-term follow-up. Online First doi 10.1136/jnnp-2012-303826]


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