Vítima de envelhecimento precoce chega à adolescência com tratamento pioneiro

A britânica Hayley Okines sofre da forma mais severa da síndrome de progeria, condição genética rara que leva a um dramático envelhecimento prematuro. Graças a um tratamento pioneiro nos Estados Unidos, Hayley conseguiu comemorar este ano seu aniversário de 13 anos.

A britânica Hayley Okines sofre da forma mais severa da síndrome de progeria, uma condição genética rara

A adolescente foi diagnosticada com a síndrome de Hutchinson-Gilford quando tinha apenas um ano de idade e, de acordo com os médicos, dificilmente chegaria à adolescência.

A progeria é causada pela mutação de um gene que leva ao acúmulo de uma proteína chamada "progerina". A proteína desencadeia um processo de envelhecimento celular excessivamente rápido.

Os pacientes com a doença passam por um processo de envelhecimento oito vezes mais rápido do que o registrado normalmente.

Síndrome só foi diagnosticada quando Hayles tinha 1 ano.

Para ser submetida ao tratamento, Hayley tem que viajar aos Estados Unidos a cada 16 semanas e, segundo ela, às vezes, a medicação a faz sentir um pouco mal. Antes de ser usado no caso de Hayley, o tratamento só havia sido testado em ratos.

Segundo o site criado por seus pais para divulgar mais informação sobre a doença, atualmente há no mundo apenas 53 crianças com a doença. Eles contam ainda que nenhum problema foi registrado durante a gravidez de Hayley.

SÍNDROME DE PROGERIA

A síndrome é extremamente rara, ocorrendo em um de cada oito milhões de nascimentos.

Enrugamento da pele, embranquecimento e queda dos cabelos, olhos proeminentes e veias cranianas salientes são algumas das características físicas da doença.

Os portadores de progeria também costumam sofrer de osteoporose, insuficiências endócrinas e cardíacas.

Segundo uma fundação que pesquisa a progeria, a maioria dos portadores morre por doenças do coração.

A idade média alcançada pelas crianças é 13 anos, com expectativa de vida dos pacientes variando entre 8 e 21 anos.

Embora tenha uma base genética a doença não é geralmente transmitida na família. Trata-se de uma mutação aleatória dos genes e as chances de uma família em que há um paciente com a síndrome, de ter outro bebê portador da doença é a mesma para qualquer outro casal ao redor do mundo.

Vacina consegue bloquear prazer da cocaína em ratos

Sistema imunológico dos animais 'aprendeu' a combater a droga. Em laboratório, efeito do medicamento durou 13 semanas.

Uma nova vacina testada nos EUA provou ser eficaz para combater o prazer causado pela cocaína. Em pesquisa financiada pelo Instituto Nacional sobre Abuso de Drogas (Nida) dos EUA, cientistas combinaram pedaços de um vírus causador do resfriado e partículas que imitam cocaína, criando um composto que induz o sistema imunológico a combater o princípio da droga antes que ele chegue ao cérebro.

No estudo – divulgado nesta terça-feira (4) na revista científica “Molecular Therapy” – os pesquisadores usaram ratos como cobaias. Nesses animais, o efeito da vacina durou 13 semanas.

“Nossos dados mostram que podemos proteger ratos dos efeitos da cocaína, e achamos que o mesmo procedimento pode ser promissor para tratar a dependência [de cocaína] em humanos”, diz o líder da pesquisa, Ronald G. Crystal, da faculdade de Medicina Weill Cornell, nos EUA.

Segundo o médico, hoje não há vacinas contra nenhum tipo de dependência química nos EUA. Ele ressalta que existem outras tentativas de criar uma vacina contra a cocaína, mas esta é a primeira vez que se consegue algo que não exija caras e múltiplas aplicações, fazendo com que seja simples o caminho para o próximo passo: testar o medicamento em humanos.

A esperança dos pesquisadores é de que a vacina seja eficaz para quem já é viciado em cocaína e esteja tentando parar de usá-la. “A vacina pode ajudá-los a parar esse hábito. Se eles usarem cocaína, uma resposta imunológica vai destruir a droga antes que ela alcance o centro de prazer do cérebro”, diz o pesquisador.

Parallels Between Cancers, Infection Suppression: Same Proteins Involved, but Cancer Takes Hold When Response Gets out of Control

ScienceDaily (Jan. 4, 2011) — Tiny parasitoid wasps can play an important role in controlling the populations of other insect species by laying their eggs inside the larvae of these species. A newly hatched wasp gradually eats the host alive and takes over its body.

The immune system response in Drosophila to a wasp infection (above) is highly restrained, resulting in a thin layer of blood cells encapsulating the egg. However, blood cancer occurs (below) when there is an out-of-control response to a chronic inflammation, with a much thicker layer of red blood cells. 

The host insect is far from defenseless, however. In Drosophila (fruit flies), larvae activate humoral immunity in the fat body and mount a robust cellular response that encapsulates and chokes off the wasp egg.

New research by Dr. Shubha Govind, professor of biology at The City College of New York, and colleagues reveals parallels between how this mechanism fights the wasp infection and the way blood cancer develops. "There are fundamental similarities in the processes," she explains. "The response to wasp infection is similar to acute inflammation while the cancer is akin to chronic inflammation in mammals, where regulation of the response to an infection also goes out of control."

Professor Govind reports that the immune system that counters wasp egg infection is highly restrained. The system works like a thermostat, with certain proteins detecting the infection and triggering the immune reactions. Once the egg has been destroyed the immune reactions come to a halt.

However, when the regulating mechanism goes haywire, cancer can develop. Through sumoylation, the correct balance between positive and negative factors is achieved, Professor Govind and colleagues report.

"There is strong evidence that the fundamental mechanism of regulation uncovered in flies also works in humans," she notes. "Because of the molecular similarities between flies and mammals, it may be possible to use flies to test drugs for potential anti-inflammatory effects in human disease." While such drugs would not cure cancer, they could control inflammation and, perhaps, delay cancer progression.

Other potential applications are in pest control for agriculture. Instead of using insecticides, parasitoids with the ability to suppress the hosts' immune systems could be used to kill insect pests. Also, insecticides could be developed that, at very low concentrations, would weaken the immune systems of host insects and enable parasitoid eggs to succeed, Professor Govind adds.

The findings were published last month in PLoS Pathogens, a peer-reviewed, open-access journal published by the Public Library of Science. Contributing scientists were: Indira Paddibhatla, Mark J. Lee, Marta E. Kalamarz and Roberto Ferrarese. The work was funded by the National Institutes of General Medicine, U.S. Department of Agriculture and PSC-CUNY.

Peptide Delivers One-Two Punch to Breast Cancer in Pre-Clinical Study

ScienceDaily (Jan. 4, 2011) — Researchers at Wake Forest University Baptist Medical Center (WFUBMC) have discovered what may become a new weapon in the fight against breast cancer. For the first time, a peptide found in blood and tissue has been shown to inhibit the growth of human breast tumors in mice, according to a study recently published in the journal Cancer Research.

Patricia E. Gallagher, Ph.D., and E. Ann Tallant, Ph.D., scientists in the Hypertension and Vascular Research Center at WFUBMC, demonstrated that the peptide angiotensin-(1-7) attacked breast cancer in two ways: by inhibiting the growth of the breast cancer cells themselves and by inhibiting the growth of cancer-associated fibroblasts (CAFs), cells found in the tumor microenvironment -- the tissue surrounding the tumor. CAFs play a vital role in tumor initiation, growth and metastases by providing structural support for the tumor cells and by producing growth factors that help the tumor cells grow.

In this study, mice were injected with human breast cancer cells to form the two most common types of breast tumors -- estrogen-receptor and HER2 sensitive. In women with breast cancer, an estimated 50 to 60 percent have estrogen-receptor sensitive tumors and 20 to 30 percent have HER2 sensitive tumors.

Once the tumors grew, the mice were injected with either angiotensin-(1-7) or saline for 18 days. In the mice treated with angiotensin-(1-7), there was a 40 percent reduction in tumor size as compared to the saline-injected mice, whose tumors grew three times their size at the initiation of treatment. Breast tumor fibrosis also was reduced by 64 to 75 percent in the mice treated with the peptide as compared to the saline-injected mice. Fibrosis is the thickening of the breast tissue around and within the tumor that acts as a scaffold to support the spread of cancer cells.

"This is the first study to show that angiotensin-(1-7) not only inhibits the growth of tumors, but also inhibits breast tumor fibrosis," Gallagher said. "Think of it as a seed and the soil around it -- the seed being the tumor and the soil being the fibrosis. You can attack the seed, or you can attack the soil, or do both, and our drug does both."

The tumor microenvironment is especially important when the cancer has metastasized, Tallant said, because drugs that are effective for treating the primary tumor often are not effective in treating a tumor growing in a different part of the body. "Our findings also suggest that angiotensin-(1-7) may enhance the effect of chemotherapeutic agents when administered in combination with other drugs by altering the microenvironment in which the tumor grows," she said.

"Because the safety of angiotensin-(1-7) was established here at Wake Forest Baptist in a recently completed trial in patients with different types of solid tumors, we hope to go to clinical trials for breast cancer relatively soon," Gallagher said.

Gallagher's and Tallant's initial research conducted at the Comprehensive Cancer Center at Wake Forest Baptist showed that angiotensin-(1-7) inhibited the growth of vascular smooth muscle cells, the cells that surround blood vessels and regulate blood pressure. Previous studies showed that patients treated with drugs to reduce blood pressure and increase angiotensin-(1-7), also had a smaller chance of developing cancer.Based on this information, Gallagher and Tallant studied the effect of the peptide on lung cancer and discovered that angiotensin-(1-7) inhibited the growth of lung tumors in mice, as well as reduced the supply of blood vessels to the growing tumor. Their latest study, as reported in Cancer Research, now shows additional effects of angiotensin-(1-7).

Both scientists and Wake Forest University Baptist Medical Center hold a patent on the use of angiotensin-(1-7) for the treatment of cancer.

Protein Wields Phosphate Group to Inhibit Cancer Metastasis; Tagging an Enzyme With Chemical Also Is Crucial to Bone Cell Formation

ScienceDaily (Jan. 4, 2011) — By sticking a chemical group to it at a specific site, a protein arrests an enzyme that may worsen and spread cancer, an international research team led by scientists at The University of Texas MD Anderson Cancer Center reports in the January issue of Nature Cell Biology.

In addition to highlighting a novel anti-cancer pathway, the team found that the same deactivation of the enzyme called EZH2 is necessary for the formation of bone-forming cells from the stem cells that make them and other tissues.

"EZH2 is overexpressed in aggressive solid tumors and tied to cancer progression and metastasis," said the paper's senior author, Mien-Chie Hung, Ph.D., professor and chair of MD Anderson's Department of Molecular and Cellular Oncology. "We have found that another protein, CDK1, deactivates EZH2."

The team's basic research findings provide a rationale for developing an EZH2 inhibitor or a drug that mimics the protein that deactivates it as new cancer drugs. "You have to understand the molecular details of cancer formation and progression to develop new therapies that improve treatment and prevention," Hung said.

In a series of experiments, the team demonstrated how CDK1 interferes with EZH2, reducing cell migration and invasion in breast cancer cell lines.

EZH2 silences gene expression by attaching a methyl group, which consists of one carbon and three hydrogen atoms, to a histone protein that is intertwined with DNA and other proteins to compose chromosomes. Genes suppressed by this methylation include tumor suppressors that would otherwise prevent cancer growth and spread.

The team showed that CDK1 short-circuits EZH2-mediated methylation by attaching a different chemical group consisting of one phosphate and three oxygen atoms to EZH2, a process called phosphorylation. And that phosphorylation has to occur at a specific amino acid on EZH2 to have this effect.

It's a matter of phosphorylation trumping methylation, Hung said. The phosphorylated version of EZH2 cannot methylate the target histone protein, so repressed genes are awakened.

Cancer cells with EZH2 that had a mutant version of the location where the phosphate group connects, preventing phosphorylation, had double the cell migration and invasion of cancer cells with the regular, unmutated version of EZH2.

Same process vital to bone formation

EZH2 plays an important normal role in a variety of biological processes. "EZH2 is crucial to embryonic development because it turns genes off and on to guide the differentiation of embryonic stem cells into tissues and organs," Hung said. Embryonic stem cells can turn into any type of cell.

In a separate set of experiments, the researchers demonstrated that phosphorylation of EZH2 is necessary to the production of bone cells (osteoblasts).

Mesenchymal stem cells can differentiate into bone, cartilage or fat cells. The team showed only those cells with EZH2 phosphorylated by CDK1 differentiated into bone cells. Genes crucial to bone formation were silenced by methlyation but awakened when CDK1 altered EZH2.

A genomewide screen to identify genes targeted by EZH2 in mesenchymal stem cells was conducted before and after the cells differentiated into bone cells. Before, more than 4,000 genes were found to bind to EZH2. After differentiation to bone cells, 30 or fewer genes bound to the protein.

"This and other recently reported studies open up drug development possibilities by either inhibiting the methyltransferase activity of EZH2 or regulating phosphorylation to indirectly regulate EZH2's activity," Hung said.

"This study also suggests a possible way to induce mesenchymal stem cell differentiation into bone cells, which may have long-term implications for regenerative medicine for bone disease," Hung said.

This project was a result of the MD Anderson/China Medical University Hospital Sister institution collaboration.

Research was supported by grants from the National Cancer Institute, Kadoorie Charitable Foundations, National Breast Cancer Foundation, Inc., and the MD Anderson/China Medical University and Hospital Sister Foundation Funds and Cancer Center of Research Excellence from Taiwan.

Co-authors with Hung and first author Yongkun Wei, Ph.D., are Jingyu Lang, Ph.D., Bin Shi, Ph.D., Cheng-Chieh Yang, D.D.S., Ph.D., and Jer-Yen Yang Ph.D., all of MD Anderson's Department of Molecular and Cellular Biology; Ya-Huey Chen, Ph.D., Long-Yuan Li, Ph.D., and Chun-Yi Lin, all of Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University and Hospital, Taichung, Taiwan; Su-Peng Yeh, M.D., Division of Hematology and Oncology, China Medical University and Hospital, and Chien-Chen Lai, Ph.D., Graduate Institute of Chinese Medical Science, China Medical Universiy and Hospital and the Institute of Molecular Biology, National Chung Hsing University, Taiwan. Hung also is affiliated with China Medical University and Hospital and with The University of Texas Graduate School of Biomedical Sciences at Houston.

Kids Frequently Exposed to Medical Imaging Procedures That Use Radiation, Study Finds

ScienceDaily (Jan. 4, 2011) — The rapid growth in use of medical diagnostic imaging, such as CT scans, has led to widespread concern about radiation exposure in adults and the potential for future cancer risk in patients undergoing these tests.

A new study led by University of Michigan researchers now shows that kids also frequently receive these types of imaging procedures during their routine clinical care, and highlights the importance of initiatives to ensure that those tests being performed are necessary and use the lowest possible doses of radiation.

"Our findings indicate that more awareness about the frequent use of these tests may be needed among care providers, hospitals and parents," says Adam L. Dorfman, M.D., clinical assistant professor of pediatrics and communicable diseases and of radiology at the U-M Medical School. "Imaging tests are a critical component of good medical care, but the high number of tests raises questions about whether we are being judicious in our use of the technology."

The results of this study were published online in the Archives of Pediatrics and Adolescent Medicine.

Despite widespread discussions about the health hazards of environmental exposures in children, radiation exposure from the frequent use of imaging procedures has received less attention, possibly due to limited contemporary data in younger patients. As such, this study identified 355,088 children under the age of 18 in five large U.S. health care markets to track how often these imaging procedures are used. The study found that over 400,000 imaging procedures were performed in just 3 years, with 42.5% of the children receiving at least one of these procedures and many undergoing multiple tests. The types of tests the investigators considered included everything from routine x-rays that use very low doses of radiation to more advanced tests, like CT scans, that require doses that are greater. Based on these data, the average child in this study population would be expected to receive approximately 7 imaging procedures utilizing radiation by age 18.

By necessity, the study focused on the numbers and types of procedures that were performed, and did not calculate specific doses of radiation that were received by each child. Data to perform such calculations are limited in children and are part of ongoing work by the team.

"What we've tried to do is raise awareness of the issue and start a national dialogue by identifying the overall scope of the problem," Dorfman says." One limitation of this type of analysis is that the clinical appropriateness of the tests could not be determined, he adds.

"The next step is to better understand when these tests really add value to the care of a child and when they do not," Dorfman says.

Among the tests that the investigators considered, CT scans are the most important from the standpoint of radiation exposure. Nearly 8% of the children in this study received a CT scan in the 3-year study period, with 3.5% of the children receiving more than one. Understanding patterns of utilization of these tests in children is important because children and infants are more susceptible than adults to the risks of radiation exposure, such as future cancers.

"Developing tissues in children are more sensitive to radiation and their longer expected life spans also allows additional time for the emergence of detrimental effects," says co-author, Reza Fazel, M.D., M.Sc., a cardiologist at the Emory School of Medicine. Fazel cautions that for any individual child undergoing a single test the risk is typically low.

"Of course, there is immense life-saving value in medical imaging, so our study doesn't suggest at all that these tests shouldn't be used in children," adds co-author Kimberly E. Applegate, M.D., vice chair for Quality and Safety in the Department of Radiology at Emory University. "We have to be smarter about how we use tests. For example, children don't always need the same radiation dose during a CT scan to get the same quality of image and information."

Investigators note that each imaging procedure should be guided by the principle of ALARA, or As Low As Reasonably Achievable, which advocates for minimizing radiation doses while still obtaining sufficient clinical information. Applegate, a member of the international Image Gently Campaign, is working with a coalition of health care organizations to raise awareness of the need to adjust radiation doses when imaging children. The Image Gently campaign promotes optimal scanning strategies to lower radiation exposure in children.

Andrew J. Einstein, M.D., Ph.D., a cardiologist at Columbia University and another coauthor, says this study should not deter parents from imaging procedures that may provide clear benefit for their children. "It should encourage discussions about the value of each imaging test that is ordered, recognizing that radiation exposure, even in small amounts, may not be risk free."

Additional authors include Harlan M. Krumholz, M.D, S.M., Yale University School of Medicine; Yongfei Wang, M.S.,Yale University School of Medicine; Emmanuel Christodoulou, Ph.D., University of Michigan Medical School; Jersey Chen, M.D., M.P.H., Yale University School of Medicine; Ramon Sanchez, M.D., University of Michigan Medical School; Brahmajee K. Nallamothu, M.D., M.P.H., University of Michigan Medical School

Funding: Dr. Einstein was supported by K12 institutional career development award KL2 RR024157 from the National Institutes of Health, by the Louis V. Gerstner Jr Scholars program, and by the Lewis Katz Cardiovascular Research Prize for a Young Investigator. Dr. Chen was supported in part by American Heart Association Clinical Research Program Award 10CRP2640075 and Agency for Healthcare Research and Quality Career Development Award 1K08HS018781-01.

Disclosure: Dr. Einstein has served as a consultant for the International Atomic Energy Agency and for GE Healthcare, has received support for other research from Spectrum Dynamics and a Nuclear Cardiology Foundation grant funded by Covidien, and has received travel funding from GE Healthcare, INVIA, Philips Medical Systems, and Toshiba America Medical Systems. Dr. Applegate has a textbook contract for Evidence-Based Imaging in Pediatrics with Springer. Dr. Krumholz is the chairman of a scientific advisory board for UnitedHealthcare.

Additional Resources: The Image Gently Campaign is an initiative of the Alliance for Radiation Safety in Pediatric Imaging. The campaign goal is to change practice by increasing awareness of the opportunities to lower radiation dose in the imaging of children. More information at:www.imagegently.org

Clostridium Bacteria Infecting Increasing Numbers of Hospitalized Children

ScienceDaily (Jan. 4, 2011) — Hospitalized children in the United States are more frequently becoming infected with the bacteria Clostridium difficile, according to a report posted online that will appear in the May print issue of Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.

C. difficile can colonize the gastrointestinal tract and lead to infection, according to background information in the article. While some infected patients have no symptoms, others develop diarrhea, toxic megacolon (extreme inflammation and distention of the large intestine), perforated bowels or other potentially fatal complications. "In recent years, the incidence of C. difficile infection, number of hospitalizations, associated deaths and severity in adults have been increasing," the authors write.

To evaluate the trends of C. difficileinfection in children, Cade M. Nylund, M.D., of Uniformed Services University of the Health Sciences, Bethesda, Md., and colleagues analyzed records of hospitalized children in a national database of patients discharged from the hospital in 1997, 2000, 2003 and 2006. The database included about 10.5 million patients, of whom 21,274 (0.2 percent) had C. difficile infection.

The number of cases increased about 15 percent each year, from 3,565 in 1997 to 7,779 in 2006. Children with C. difficileinfection had an increased risk of death or colectomy (surgery to remove all of part of the colon), longer hospital stays and higher hospitalization charges.

Some children appeared more likely to become infected, including those who were white, lived in the West or in urban areas, had private insurance or had other co-occurring diseases, such as inflammatory bowel disease. The risk of infection was lower among black or Hispanic children, those who lived in the South, those admitted to rural hospitals, those with Medicaid/Medicare insurance and those who had self-pay or no-pay insurance status.

Unlike recent trends in adults, however, the authors did not observe an increase in severity over time among children infected with C. difficile.

The increased risk of C. difficile infection may be due to a widespread dissemination of a more virulent strain of the bacteria, the authors note. "There may also be increasing awareness among health care providers, leading to increased testing in symptomatic patients," they write.

"The population-based data in our study provide additional evidence that C. difficile infection cases have a significant effect on the pediatric population," the authors conclude. "Our study supports previous reports that C. difficile infection is increasing among hospitalized children and provides a background for understanding changing trends and risk factors of C. difficile infection in children. Increasing awareness of these risk factors and of an upward trend in hospitalized children with C. difficile infection is the first step in controlling this important infection.

Brain Imaging Studies Examine How Anti-Smoking Medications May Curb Cravings

ScienceDaily (Jan. 4, 2011) — The smoking cessation medications bupropion and varenicline may both be associated with changes in the way the brain reacts to smoking cues, making it easier for patients to resist cravings, according to two reports posted online that will appear in the May print issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

"Environmental cues associated with nicotine reinforcement induce cigarette craving, which propagates smoking habits in smokers and relapse in abstinent individuals," the authors write as background information in one of the articles. "Human brain imaging studies using functional magnetic resonance imaging (fMRI) and positron emission tomography scanning have provided insight into brain regions associated with cue-induced cigarette craving. Nicotine-dependent smokers exhibit activation in brain regions related to attention (prefrontal cortex), emotion (amygdala), reward (ventral tegmental area) and motivation (striatum) while viewing cigarette-related cues."

Bupropion, originally marketed as an antidepressant, was found to enhance smoking cessation in patients with depression and is now one of the most common therapies for smoking cessation in the world. It is known to reduce cravings in response to smoking cues, but its mechanism for doing so is not well understood. In one study, Christopher S. Culbertson, Ph.D., of University of California, Los Angeles, and colleagues assessed changes in brain activation in response to smoking cues among 30 smokers who were randomly assigned to take either bupropion or placebo for eight weeks.

Participants underwent fMRI scans within one week of joining the study and again at the end of the eight-week treatment period. During the scans, they were shown 45-second videos that contained either smoking cues-actors and actresses smoking in a variety of settings-or neutral cues, with similar settings but no smoking behaviors. Participants also used a response box with five buttons on it to report how strongly they craved cigarettes immediately after watching each video.

Patients who were treated with bupropion reported less craving in response to smoking cues than did patients who received placebo. Those taking bupropion also showed reduced activation in areas of the brain known to be associated with cravings, including limbic and prefrontal regions. Among all the participants, regardless of treatment, reports of cravings aligned with fMRI images-that is, those who showed reduced activation in craving-related areas also reported feeling fewer cravings.

"These results demonstrate that treatment with bupropion is associated with an improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions," the authors conclude.

In another article, Teresa Franklin, Ph.D., of University of Pennsylvania, Philadelphia, and colleagues studied brain responses to varenicline, a first-line smoking cessation medication. Varenicline reduces withdrawal symptoms and the reinforcement received from nicotine while smoking. The researchers studied whether it would also aid in reducing brain and craving responses when smokers are exposed to smoking cues. They used a neuroimaging technique called perfusion fMRI, which allows the measurement of longitudinal changes induced by a medication during smoking cue exposure and also in the brain in the resting condition.

Twenty-two smokers received either varenicline or placebo in a three-week randomized medication regimen. The brains of smokers were imaged before and after the medication regimen, while 'at rest' and while viewing 10-minute video clips that contained either smoking cues or non-smoking cues, and they also reported their cravings. Smokers were still smoking during the medication regimen to explicitly examine varenicline effects on cue reactivity independent of withdrawal, which also affects brain activity.

In scans performed before the medication regimen, smoking cues activated brain areas involved in drug-motivation, such as the ventral striatum and medial orbitofrontal cortex, and also elicited reports of craving. After the medication regimen, similar patterns of activity persisted in patients who had taken placebo, whereas those who received varenicline experienced a reduction in brain activity in those regions and in self-reported craving.

In participants who took varenicline, brain activity in the resting condition was selectivity increased in a region known as the lateral orbitofrontal cortex, which is implicated in inhibiting behavior that predicts reward (such as smoking cues). Importantly, increased activation in this area predicted the blunted response in the medial orbitofrontal cortex and ventral striatum, explicitly demonstrating the mechanism underlying varenicline's property to reduce the effects of smoking cues on both the brain and craving.

"The results of our study reveal a distinctive new action that likely contributes to its clinical efficacy," the authors conclude. "Unsuccessful smoking cessation is more prevalent in individuals with psychiatric illness, suggesting that they have greater difficulty quitting. Varenicline and other medications that can reduce both withdrawal and cue reactivity may be of special benefit to these subgroups who may also be more vulnerable to relapse in the presence of smoking cues."