Archive for the ‘Addiction’ Category

sn-epigenetic

Cigarettes leave you with more than a smoky scent on your clothes and fingernails. A new study has found strong evidence that tobacco use can chemically modify and affect the activity of genes known to increase the risk of developing cancer. The finding may give researchers a new tool to assess cancer risk among people who smoke.

DNA isn’t destiny. Chemical compounds that affect the functioning of genes can bind to our genetic material, turning certain genes on or off. These so-called epigenetic modifications can influence a variety of traits, such as obesity and sexual preference. Scientists have even identified specific epigenetic patterns on the genes of people who smoke. None of the modified genes has a direct link to cancer, however, making it unclear whether these chemical alterations increase the risk of developing the disease.

In the new study, published in Human Molecular Genetics, researchers analyzed epigenetic signatures in blood cells from 374 individuals enrolled in the European Prospective Investigation into Cancer and Nutrition. EPIC, as it’s known, is a massive study aimed at linking diet, lifestyle, and environmental factors to the incidence of cancer and other chronic diseases. Half of the group consisted of people who went on to develop colon or breast cancer 5 to 7 years after first joining the study, whereas the other half remained healthy.

The team, led by James Flanagan, a human geneticist at Imperial College London, discovered a distinct “epigenetic footprint” in study subjects who were smokers. Compared with people who had never smoked, these individuals had fewer chemical tags known as methyl groups—a common type of epigenetic change—on 20 different regions of their DNA. When the researchers extended the analysis to a separate group of patients and mice that had been exposed to tobacco smoke, they narrowed down the epigenetic modifications to several sites located in four genes that have been weakly linked to cancer before. All of these changes should increase the activity of these genes, Flanagan says. It’s unclear why increasing the activity of the genes would cause cancer, he says, but individuals who don’t have cancer tend not to have these modifications.

The study is the first to establish a close link between epigenetic modifications on a cancer gene and the risk of developing the disease, says Robert Philibert, a behavioral geneticist at the University of Iowa in Iowa City. “To the best of my knowledge, no previous genome-wide epigenetics study has taken such efforts from initial discovery to replication to experimental validation,” adds Lutz Breitling, an epidemiologist at the German Cancer Research Center in Heidelberg, Germany.

The work may lead to new ways to asses cancer risks from smoking. “Previous research into smoking has often asked people to fill out questionnaires, … which have their obvious drawbacks and inaccuracies,” Flanagan says. The new study, he says, may make it possible for doctors to quantify a person’s cancer risk simply through an epigenetic analysis of their DNA.

http://news.sciencemag.org/sciencenow/2012/12/smoking-smothers-your-genes.html

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

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How far should doctors go in attempting to cure addiction? In China, some physicians are taking the most extreme measures. By destroying parts of the brain’s “pleasure centers” in heroin addicts and alcoholics, these neurosurgeons hope to stop drug cravings. But damaging the brain region involved in addictive desires risks permanently ending the entire spectrum of natural longings and emotions, including the ability to feel joy.

In 2004, the Ministry of Health in China banned this procedure due to lack of data on long term outcomes and growing outrage in Western media over ethical issues about whether the patients were fully aware of the risks.

However, some doctors were allowed to continue to perform it for research purposes—and recently, a Western medical journal even published a new study of the results. In 2007, The Wall Street Journal detailed the practice of a physician who claimed he performed 1000 such procedures to treat mental illnesses such as depression, schizophrenia and epilepsy, after the ban in 2004; the surgery for addiction has also since been done on at least that many people.

The November publication has generated a passionate debate in the scientific community over whether such research should be published or kept outside the pages of reputable scientific journals, where it may find undeserved legitimacy and only encourage further questionable science to flourish.

The latest study is the third published since 2003 in Stereotactic and Functional Neurosurgery, which isn’t the only journal chronicling results from the procedure, which is known as ablation of the nucleus accumbens. In October, the journal World Neurosurgery also published results from the same researchers, who are based at Tangdu Hospital in Xi’an.

The authors, led by Guodong Gao, claim that the surgery is “a feasible method for alleviating psychological dependence on opiate drugs.” At the same time, they report that more than half of the 60 patients had lasting side effects, including memory problems and loss of motivation. Within five years, 53% had relapsed and were addicted again to opiates, leaving 47% drug free.

(MORE: Addicted: Why We Get Hooked)

Conventional treatment only results in significant recovery in about 30-40% of cases, so the procedure apparently improves on that, but experts do not believe that such a small increase in benefit is worth the tremendous risk the surgery poses.  Even the most successful brain surgeries carry risk of infection, disability and death since opening the skull and cutting brain tissue for any reason is both dangerous and unpredictable. And the Chinese researchers report that 21% of the patients they studied experienced memory deficits after the surgery and 18% had “weakened motivation,” including at least one report of lack of sexual desire. The authors claim, however, that “all of these patients reported that their [adverse results] were tolerable.” In addition, 53% of patients had a change in personality, but the authors describe the majority of these changes as “mildness oriented,” presumably meaning that they became more compliant. Around 7%, however, became more impulsive.

The surgery is actually performed while patients are awake in order to minimize the chances of destroying regions necessary for sensation, consciousness or movement.  Surgeons use heat to kill cells in small sections of both sides of the brain’s nucleus accumbens.  That region is saturated with neurons containing dopamine and endogenous opioids, which are involved in pleasure and desire related both to drugs and to ordinary experiences like eating, love and sex.

(MORE: A Drug to End Drug Addiction)

In the U.S. and the U.K., reports the Wall Street Journal, around two dozen stereotactic ablations are performed each year, but only in the most intractable cases of depression and obsessive-compulsive disorder and after extensive review by institutional review boards and intensive discussions with the patient, who must acknowledge the risks. Often, a different brain region is targeted, not the nucleus accumbens. Given the unpredictable and potentially harmful consequences of the procedure, experts are united in their condemnation of using the technique to treat addictions. “To lesion this region that is thought to be involved in all types of motivation and pleasure risks crippling a human being,” says Dr. Charles O’Brien, head of the Center for Studies of Addiction at the University of Pennsylvania.

David Linden, professor of neuroscience at Johns Hopkins and author of a recent book about the brain’s pleasure systems calls the surgery “horribly misguided.”  He says “This treatment will almost certainly render the subjects unable to feel pleasure from a wide range of experiences, not just drugs of abuse.”

But some neurosurgeons see it differently. Dr. John Adler, professor emeritus of neurosurgery at Stanford University, collaborated with the Chinese researchers on the publication and is listed as a co-author.  While he does not advocate the surgery and did not perform it, he believes it can provide valuable information about how the nucleus accumbens works, and how best to attempt to manipulate it. “I do think it’s worth learning from,” he says. ” As far as I’m concerned, ablation of the nucleus accumbens makes no sense for anyone.  There’s a very high complication rate. [But] reporting it doesn’t mean endorsing it. While we should have legitimate ethical concerns about anything like this, it is a bigger travesty to put our heads in the sand and not be willing to publish it,” he says.

(MORE: Anesthesia Study Opens Window Into Consciousness)

Dr. Casey Halpern, a neurosurgery resident at the University of Pennsylvania makes a similar case. He notes that German surgeons have performed experimental surgery involving placing electrodes in the same region to treat the extreme lack of pleasure and motivation associated with otherwise intractable depression.  “That had a 60% success rate, much better than [drugs like Prozac],” he says. Along with colleagues from the University of Magdeburg in Germany, Halpern has just published a paper in the Proceedings of the New York Academy of Sciences calling for careful experimental use of DBS in the nucleus accumbens to treat addictions, which have failed repeatedly to respond to other approaches. The paper cites the Chinese surgery data and notes that addiction itself carries a high mortality risk.

DBS, however, is quite different from ablation.  Although it involves the risk of any brain surgery, the stimulation itself can be turned off if there are negative side effects, while surgical destruction of brain tissue is irreversible. That permanence—along with several other major concerns — has ethicists and addiction researchers calling for a stop to the ablation surgeries, and for journals to refuse to publish related studies.

Harriet Washington, author of Medical Apartheid:  The Dark History of Medical Experimentation on Black Americans from Colonial Times to the Present, argues that by publishing the results of unethical studies, scientists are condoning the questionable conditions under which the trials are conducted. “When medical journals publish research that violates the profession’sethical guidelines, this serves not only to sanction such abuses, but to encourage them,” she says. “In doing so, this practice encourages a relaxing of moral standards that threatens all patients and subjects, but especially  the medically vulnerable.”

(MORE: Real-Time Video: First Look at a Brain Losing Consciousness Under Anesthesia)

Shi-Min Fang, a Chinese biochemist who became a freelance journalist and recently won the journal Nature‘s Maddox prize for his exposes of widespread fraud in Chinese research, has revealed some of the subpar scientific practices behind research conducted in China, facing death threats and, as the New York Times reported, a beating with a hammer. He agrees that publishing such research only perpetuates the unethical practices. Asked by TIME to comment on the addiction surgery studies, Fang writes that publishing the research, particularly in western journals, “would encourage further unethical research, particularly in China where rewards for publication in international journals are high.”

While he doesn’t have the expertise to comment specifically on the ablation data, he says “the results of clinical research in China are very often fabricated. I suspect that the approvals by Ethics Committee mentioned in these papers were made up to meet publication requirement. I also doubt if the patients were really informed in detail about the nature of the study.” Fang also notes that two of the co-authors of the paper are advertising on the internet in Chinese, offering the surgery at a cost of 35,000 renminbi, about $5,600.  That’s more than the average annual income in China, which is about $5,000.

Given the available evidence, in fact, it’s hard to find a scientific justification for even studying the technique in people at all. Carl Hart, associate professor of psychology at Columbia University and author of the leading college textbook on psychoactive drugs, says animal studies suggest the approach may ultimately fail as an effective treatment for addiction; a 1984 experiment, for example, showed that destroying the nucleus accumbens in rats does not permanently stop them from taking opioids like heroin and later research found that it similarly doesn’t work for curbing cocaine cravings. Those results alone should discourage further work in humans. “These data are clear,” he says, “If you are going to take this drastic step, you damn well better know all of the animal literature.” [Disclosure:  Hart and I have worked on a book project together].

(MORE: Top 10 Medical Breakthroughs of 2012)

Moreover, in China, where addiction is so demonized that execution has been seen as an appropriate punishment and where the most effective known treatment for heroin addiction— methadone or buprenorphine maintenance— is illegal, it’s highly unlikely that addicted people could give genuinely informed consent for any brain surgery, let alone one that risks losing the ability to feel pleasure. And even if all of the relevant research suggested that ablating the nucleus accumbens prevented animals from seeking drugs, it would be hard to tell from rats or even primates whether the change was due to an overall reduction in motivation and pleasure or to a beneficial reduction in desiring just the drug itself.

There is no question that addiction can be difficult to treat, and in the most severe cases, where patients have suffered decades of relapses and failed all available treatments multiple times, it may make sense to consider treatments that carry significant risks, just as such dangers are accepted in fighting suicidal depression or cancer.  But in the ablation surgery studies, some of the participants were reportedly as young as 19 years old and had only been addicted for three years.  Addiction research strongly suggests that such patients are likely to recover even without treatment, making the risk-benefit ratio clearly unacceptable.

The controversy highlights the tension between the push for innovation and the reality of risk. Rules on informed consent didn’t arise from fears about theoretical abuses:  they were a response to the real scientific horrors of the Holocaust. And ethical considerations become especially important when treating a condition like addiction, which is still seen by many not as an illness but as a moral problem to be solved by punishment.  Scientific innovation is the goal, but at what price?
Read more: http://healthland.time.com/2012/12/13/controversial-surgery-for-addiction-burns-away-brains-pleasure-center/#ixzz2ExzobWQq

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

 

Eight years ago, the Multnomah County Sheriff’s Office launched a campaign called “the Faces of Meth” to address Oregon’s methamphetamine problem. The images showed the jarring effects of meth on addicts’ faces through before-and-after pictures from their arrest records.

Rehabs.com recently followed suit with this infographic. Warning: these images are disturbing.

 

meth before after rehab.com

Rehabs.com

 

 

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Read more: http://www.businessinsider.com/new-faces-of-meth-ads-are-utterly-harrowing-2012-12#ixzz2E7zSezR1

drinking_drosophila

Rejection stinks. It literally hurts. But worse, it has an immediate and negative impact on our brains, producing withdrawal symptoms as if we’re quitting a serious addiction cold turkey. It’s no wonder, then, that we are tempted to turn to drugs to makeourselves feel better. But we’re not the only species that drowns our sorrows when we’re lonely – as a new study in Science reveals, rejected Drosophila do, too. Scientists have found not only will these sexually frustrated flies choose to consume more alcohol than their happily mated peers, sex and alcohol consumption activate the same neurological pathway in their brains.

Drosophila melanogaster males sure know how to woo a lady. When placed in the same container as a potential mate, a male fly will play her a delicate love song by vibrating one wing, caress her rear end, and gently nuzzle her most private of parts with his proboiscis to convince her that he is one heck of a lover. But even the most romantic fly can’t convince an already mated female Drosophila to give up the goods, so scientists were able to use the girls’ steely resolve to see how rejection affects fly drinking behavior.

“Alcohol is one of the most widely used and abused drugs in the world,” explains lead author Galit Shohat-Ophir. “The fruit fly Drosophila melanogaster is an ideal model organism to study how the social environment modulates behavior.” Previous studies have found that Drosophila melanogaster exhibit complex addiction-like behaviors. So in the controlled setting of Ulrike Heberlein’s lab at the University of California San Francisco, researchers paired male fruit flies with three types of females: 1) unmated females, which were willing and happy to mate; 2) mated females, which actively rejected the men; and 3) decapitated females, which didn’t actively reject the guys but, well, weren’t exactly willing partners either. After the flies were satisfied or frustrated, they were offered regular food and food spiked with ethanol, and the researchers measured which type they preferred to see if there was any connection between sex and drinking.

The flies that were rejected drank significantly more than their satisfied peers, but so did the ones paired with incapacitated girls, suggesting that it wasn’t the social aspect of rejection but sexual deprivation that drives male flies to increase their ethanol consumption (see the video at the end!). This alcoholic behavior was very directly related to the guy fly ever getting laid, for even after days of blue balls, if he was allowed to spend some time with a willing woman, he no longer preferred the spiked food.

What the scientists really wanted to understand, though, was why. What drives a frustrated fly to the flask? So to look at the underlying mechanism of this phenomenon, the scientists examined the flies’ brains. A body of scientific literature has connected one particular neurotransmitter, neuropeptide F (NPF), to ethanol-related behaviors in Drosophila, so it was a logical place to start. A very similar neurotransmitter in our brains, called neuropeptide Y (NPY), is linked to alcoholism.

Increased expression of NPF in mated male brains, as shown through immunochemistry.

The team found that sexual frustration caused an immediate decrease in the expression of NPF, while sex increased expression. Furthermore, when they used genetics to artificially knock down NPF levels in the satisfied flies, they drank as much as their not-so-satisfied friends. Similarly, when the researchers artificially increased NPF levels, flies stayed sober. This is the first time NPF levels have connected sexual activity to drinking. Clearly, NPF levels controlled the flies’ desire to drink, so the team further explored how NPF works in the fly’s brain.

Many animals, including ourselves, possess a neurological reward system which reinforces good behavior. Through this system, we ascribe pleasure or positive feelings to things we do that are necessary for species survival, including sex, eating, and social interaction. Drugs tap into this system, stimulating pleasure which can lead to addiction. Previous studies have shown that flies find intoxication rewarding, so the researchers hypothesized that NPF may play a role in the reward system.

Preference tests showed that artificially increasing NPF levels in the absence of sex or ethanol was rewarding to the flies, confirming the scientists’ hypothesis. This was further supported by the discovery that constantly activating NPF abolished the flies’ tendency to consider ethanol rewarding.

“NPF is a currency of reward” explains Shohat-Ophir. High NPF levels signal good behavior in Drosophila brains, thus reinforcing any activities which led to that state. This is a truly novel discovery, for while NPF and the mammal version, NPY, have been linked to alcohol consumption, no animal model has ever placed NPF/NPY in the reward system.

Understanding the role of NPF in reward-seeking behaviors may lead to better treatments for addicts. “In mammals, including humans, NPY may have a similar role [as NPF],” says Shohat-Ophir. “If so, one could argue that activating the NPY system in the proper brain regions might reverse the detrimental effects of traumatic and stressful experiences, which often lead to drug abuse.” Already, NPY and drugs that affect the function of its receptors are in clinical trials for anxiety, PTSD, mood disorders and obesity. This study suggests that perhaps they should be tested as treatment for alcoholism, too, as well as other reward-based addictions.

Research: Shohat-Ophir, G, KR Kaun & R Azanchi (2012). Sexual Deprivation Increases Ethanol Intake in Drosophila. Science 335: 1351-1355.

Click  http://blogs.scientificamerican.com/science-sushi/2012/03/15/flies-drink-upon-rejection/

to view a sequence of  three videos that show a male fly courting and successfully mating with a female fly, another male fly being rejected by a female, and a male choosing to consume an alcohol-infused solution over a non-alcohol solution. Video © Science/AAAS

 

According to recent research sponsored by SecurEnvoy, an internet security firm, more people feel anxious and tense when they are out of reach of their phone — and the younger they are, the more likely the stress.

Known as “nomophobia,” or “no mobile-phone phobia,” a recent online survey of 1,000 people in the UK found that almost two thirds (66%) of respondents were afflicted, a rise of 11% when compared to a similar study four years ago.

“Some people get panic attacks when they are not with their phones,” said Michael Carr-Gregg, an adolescent psychologist working in Melbourne.

“Others become very anxious and make all endeavors to locate the mobile phone. I have clients who abstain from school or their part-time jobs to look for their phones when they cannot find them in the morning.”

CNN Photos: De-Vice: Our mobile addiction

According to the survey, the younger you are, the more prone you are to nomophobia. The youngest age group (18 -24) tops the nomophobic list at 77%, which is 11% more than that of the next group — those aged 25-34.

“This is the most tribal generation of young people,” said Carr-Gregg. “Adolescents want to be with their friends on a 24-hour basis.”

Women are also more likely to be unnerved by cell phone separation, with 70% of respondents reporting the malady compared to 61% of men. Andy Kemshall, the CTO and co founder of secure Envoy, believes that may be because men are more likely to have two phones and are less likely to misplace both — 47% of men carry two phones, compared to only 33% of women.

Major drivers of nomophobia include boredom, loneliness, and insecurity, said Carr-Gregg, while some young nomophobes cannot bear solitude. “Many of my clients go to bed with their mobile phones while sleeping just like how one will have the teddy bear in the old days,” he said.

“While teddy doesn’t communicate, the phone does,” said Carr-Gregg, adding insomnia to the list of potential problems.

“This reduced the amount of time to reflect,” he said. “Some kids cannot entertain themselves. The phone has become our digital security blanket.”

As smartphone penetration spreads across the globe, so does nomophobia. On a visit to Singapore in February this year, Carr-Gregg spoke to students from a peer support group at the United World College and identified similar problems.

“There is no doubt that nomophobia is international,” he said. “[But] without phones, there will not be nomophobia.”

Meanwhile, Indian researchers have also evaluated mobile phone dependence among students at M.G.M. Medical College and the associated hospital of central India. India, after China, is the second largest mobile phone market in the world. The Telecom Regulatory Authority of India (TRAI) reported that there were 884.37 million mobile connections in India as of November, while China had 963.68 million.

The cross-sectional study, published by the Indian Journal of Community Medicine three years ago, recruited 200 medical students and scholars. About one in five students were nomophobic, results showed. The study claimed that the mobile phone has become “a necessity because of the countless perks that a mobile phone provides like personal diary, email dispatcher, calculator, video game player, camera and music player.”

“There is an increase in the nomophobic population in India because the number of mobile phone users has increased,” said Dr. Sanjay Dixit, one the researchers and the head of the Indian Journal of Community Medicine. “We are currently doing another research on mobile phone dependency, it’s not published yet, but analysis shows that about 45% of the Indian population, not just medical students, is nomophobic.”

With the augmented ownership and usage of smartphones among adolescents, Dixit says the young population is more at risk, partly because they can access the Internet through phones more easily, increasing the time spent on phones.

“We found out that people who use mobile phones for more than three hours a day have a higher chance of getting nomophobia,” he said, warning this can pose potential dangers.

Accidents lurk while nomophobes fix their attention on phones. According to Dixit, up to 25% nomophobes reported accidents while messaging or talking on the phone, which includes minor road accidents, falling while going upstairs or downstairs and stumbling while walking. More than 20% also reported pain in the thumbs due to excessive texting.

“One could look at this as a form of addiction to the phone,” said Eric Yu Hai Chen, a psychiatrist and professor at The University of Hong Kong. “The fear is part of the addiction. The use of hand phone has some features that predispose this activity to addiction, similar to video games, naming, easy access.”

To tackle anxiety and accidents induced by phones, Dixit suggests switching off the phone, especially while driving. “People can also carry a charger all the time,” he said. “Our study shows that the no-battery-situation upsets nomophobes the most.

“People can also prepay phone cards for emergency calls and credit balance in phones to ensure a constant and functioning network,” he said. Other solutions include supplying friends with an alternate contact number and storing important phone numbers somewhere else as backups.

“Enforcing a period when handset is turned off can help loosen its hold over everyday life,” said Dixit. Sometimes, the problem can even be the cure.

“One of my clients actually makes use mobile phone apps to deal with anxiety,” said Carr-Gregg. “It’s called iCounselor Anxiety.”

The launch of the app presents users with a scale to rate their anxiety levels from 1 to 10, where 10 is “panicked.” After choosing the level, ten recommendations of calming activities will be suggested, followed by instructions to change the user’s thoughts, so to change subsequent feelings.

“It is almost like having a psychologist in your phone,” said Carr-Gregg.

Prevalent it may be, nomophobia, however, is not yet a qualified phobia.

“Nomophobia is not included in the DSM [Diagnostic and Statistical Manual of Mental Disorders] yet,” said Dixit. “But it is an up coming problem. For the first time on this continent [India], we are trying to make it more scientific,” he added, referring to his undergoing research on nomophobic India.

http://www.cnn.com/2012/03/06/tech/mobile/nomophobia-mobile-addiction/index.html?hpt=hp_c4