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    <recommendedItem id="20100101_19_341"
                     title="Doctor&apos;s Orders: Brain&apos;s Wiring Makes Change Hard"
                     score="0.009"
                     href="http://www.medpagetoday.com/Psychiatry/Addictions/tb/18207?impressionId=1265744585390"
                     
      &lt;p&gt;Doctor&apos;s Orders&lt;em&gt; is a feature in the collaboration between &lt;/em&gt;MedPage Today &lt;em&gt;and&lt;/em&gt; ABC News&lt;em&gt;. In this monthly segment we explore medical issues of interest to physicians and their patients alike. This month, we look at addiction and addictive behaviors, and what neuroimaging studies have revealed about why it&apos;s so hard to break bad habits. &lt;/em&gt;&lt;/p&gt;&lt;hr&gt;

&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;

&lt;p&gt;By the end of January, many New Year&apos;s resolutions have been tossed out with the leftover holiday cookies. That&apos;s because change is hard  --  and neuroscientists are learning why.&lt;br&gt;
&lt;br&gt;Advances in neuroimaging have enabled researchers to peer inside the brains of addicts and patients with addictive behaviors. They can see in real-time what gets patients hooked: how the brain&apos;s reward system  --  based largely on the neurotransmitter dopamine  --  thirsts for more, while inhibitory control centers experience a system failure.&lt;br&gt;
&lt;br&gt;The pattern is similar across all kinds of behaviors  --  from cocaine and tobacco addiction to overeating. That&apos;s why changing your mind may be the first step toward breaking a habit, but altering the brain&apos;s neural machinery is the real challenge.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Hijacked Pathways&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Drug-taking and other addictive behaviors &quot;hijack&quot; the brain&apos;s reward system, says Petros Levounis, MD, director of the Addiction Institute of New York at St. Luke&apos;s and Roosevelt Hospitals in Manhattan.&lt;/p&gt;
&lt;p&gt;In normal patients, dopamine plays a major role in motivation and reward, surging before and during a pleasurable activity  --  say, eating or sex  --  to make patients want to repeat a behavior that&apos;s crucial to the survival of the species.&lt;/p&gt;
&lt;p&gt;Dopaminergic pathways connect the limbic system, responsible for emotion, with the hippocampus, etching rewarding behaviors into the brain by creating strong, salient memories.&lt;/p&gt;
&lt;p&gt;The problem arises when the memory and the craving to recapture it takes over a person&apos;s life.&lt;/p&gt;
&lt;p&gt;&quot;Imagine what a strong hold these hijacked reward pathways take on our brains and our whole existence when they&apos;re so closely connected, geographically and anatomically speaking, with our memories and our emotions,&quot; Levounis says.&lt;/p&gt;
&lt;p&gt;As the dopamine surge repeats and repeats, it gains speed, but the brakes begin to fail: Normal function in the brain&apos;s frontal lobes, responsible for inhibitory control and executive functioning (read: willpower), tends to decrease in addicts.&lt;/p&gt;
&lt;p&gt;&quot;Ultimately,&quot; Levounis says, &quot;the war on drugs is a war between the hijacked reward pathways that push the person to want to use, and the frontal lobes, which try to keep the beast at bay. That is the essence of addiction.&quot;&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Similar Patterns&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;These neural pathways have been well studied in the brains of hardcore addicts. Now, researchers say they see similar pathways involved in other bad behaviors.&lt;/p&gt;
&lt;p&gt;Gene-Jack Wang, MD, of Brookhaven National Laboratory on New York&apos;s Long Island, has conducted several brain imaging studies of obese patients using PET-CT scans.&lt;/p&gt;
&lt;p&gt;The scans have revealed similarities in brain activity  --  or a lack thereof  --  between patients addicted to cocaine or alcohol, and those &quot;addicted&quot; to eating. Normally, the PET scan lights up when a contrast of radioactive glucose is metabolized, revealing an area of red activity in the center of the brain.&lt;/p&gt;
&lt;p&gt;But in both drug-addicted and obese patients, the scans show very little red activity, because there aren&apos;t enough receptors to which the radioactive glucose can bind. Wang says the decreased availability of dopamine receptors is the brain&apos;s way of coping with a constant dopamine overload.&lt;/p&gt;
&lt;p&gt;&quot;If a person constantly has an excess of dopamine, the brain will down-regulate,&quot; Wang says, explaining the principle commonly referred to as tolerance. &quot;Once the system is down-regulated, we have to do more in order to get the same amount of feeling in our normal state.&quot;&lt;/p&gt;
&lt;p&gt;Thus, obese patients &quot;will want to eat more in order to compensate for their down-regulated system.&quot;&lt;/p&gt;
&lt;p&gt;In other experiments, Wang and his colleagues have also found that a higher body mass index (BMI) correlated with lower prefrontal cortex function  --  the area associated with inhibitory control.&lt;/p&gt;
&lt;p&gt;&quot;If they&apos;re obese,&quot; Wang said, &quot;they have a problem controlling their eating behaviors.&quot;&lt;/p&gt;
&lt;p&gt;Those studies also revealed that a higher BMI was linked to a decrease in memory and executive functioning.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Out of Control&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Ed Susman was 293 pounds when he decided to join a clinical trial for an investigational weight-loss drug and chronicle his year-long experience for &lt;em&gt;MedPage Today&lt;/em&gt;. (See &lt;a href=&quot;http://www.medpagetoday.com/PrimaryCare/Diabetes/8125&quot; mce_href=&quot;http://www.medpagetoday.com/PrimaryCare/Diabetes/8125&quot; target=&quot;_blank&quot;&gt;Journalist Participant to Present Insider View of Weight-Loss Trial&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Eating, to him, was a &quot;compulsion&quot;  --  as was biting his nails, a habit he picked up at age 4.&lt;/p&gt;
&lt;p&gt;Over the course of the trial, not only did Susman lose 52 pounds, he also stopped his nail-biting.&lt;/p&gt;
&lt;p&gt;He doesn&apos;t yet know if he was in the drug arm of the trial, but he strongly suspects he wasn&apos;t experiencing a placebo effect.&lt;/p&gt;
&lt;p&gt;&quot;I believe I was on the drug because it controlled a compulsion that I had had for 50 years,&quot; Susman says of the nail-biting. &quot;This stopped it cold.&quot;&lt;/p&gt;
&lt;p&gt;Unfortunately, he says, the same didn&apos;t happen with his eating habits, but he&apos;s gained back only 10 of those 52 pounds in the year since his participation in the trial ended.&lt;/p&gt;
&lt;p&gt;The still-investigational drug is lorcaserin  --  a combination of benzazepine and hydrochloride, two neurological agents. Susman says it is &quot;supposed to improve your willpower, your ability to overcome compulsions.&quot;&lt;/p&gt;
&lt;p&gt;Lorcaserin is a selective 5-HT&lt;sub&gt;2C&lt;/sub&gt; receptor agonist, working through the serotonin system, which regulates appetite, mood, and motor behavior.&lt;/p&gt;
&lt;p&gt;Two other investigational obesity drugs target the dopamine reward system  --  Contrave, which is a combination of bupropion and naltrexone, and Qnexa, which combines phentermine and topiramate.&lt;/p&gt;
&lt;p&gt;&quot;Some medications that have used similar dopamine modulation, until now, have failed,&quot; Wang said. &quot;These two companies are using the command of the modulation of the dopamine system with other neurological systems, such as the opiate or norepinephrine system. According to the trials, they&apos;ve been very effective.&quot;&lt;/p&gt;
&lt;p&gt;Wang called the new medications &quot;a bright light for the treatment of obesity.&quot;&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Kicking the Habit&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Basically, the idea of medications that act on the dopamine system is &quot;to cool down those reward pathways,&quot; Levounis says. There are two strategies for doing so: an agonist strategy, or an antagonist strategy.&lt;/p&gt;
&lt;p&gt;The agonist strategy is &quot;feeding the beast, providing activity in the cell so that the cravings go down,&quot; Levounis said. Classic examples are nicotine patches, or methadone for opioid dependence.&lt;/p&gt;
&lt;p&gt;On the other hand, the antagonist strategy is to block the receptors. Naltrexone, for example, will block opioid receptors so that the drug addict won&apos;t feel anything if he or she attempts to get high.&lt;/p&gt;
&lt;p&gt;&quot;After a while, you say, &apos;This is not worth my time, my money, my trouble,&apos; so you stop using,&quot; Levounis explains.&lt;/p&gt;
&lt;p&gt;These have been the two main strategies in addiction pharmacotherapy, but there&apos;s now a &quot;third avenue&quot;  --  the partial agonist approach.&lt;/p&gt;
&lt;p&gt;The partial agonist is one molecule that blocks most receptors while still providing just a little bit of an &quot;oomph&quot; to calm cravings. That&apos;s how varenicline (Chantix) helps smokers quit, and how buprenorphine gets junkies off heroin or other opioids.&lt;/p&gt;
&lt;p&gt;But what about inhibitory control? What if medications could ramp up will power?&lt;/p&gt;
&lt;p&gt;&quot;It&apos;s an area of active research,&quot; Levounis says. &quot;There are some medications proposed, but nothing to write home about.&quot;&lt;/p&gt;
&lt;p&gt;He said treatment is typically twofold. For addicts, psychiatrists will try to &quot;cool down&quot; the reward pathways, often with medication. Then, they target the diminished frontal lobes.&lt;/p&gt;
&lt;p&gt;&quot;We try to beef up the frontal lobes as much as we can, and we do that with psychotherapy,&quot; Levounis said.&lt;/p&gt;
&lt;p&gt;Researchers agree that psychotherapy is key to regaining self-control, and it&apos;s the predominant treatment used in patients with addictive behaviors.&lt;/p&gt;
&lt;p&gt;Mark Smaller, PhD, a psychoanalyst in private practice in Chicago, said psychotherapy often reveals an underlying cause for an addiction or compulsive behavior. Usually, it&apos;s anxiety or depression.&lt;/p&gt;
&lt;p&gt;Acknowledging those problems may help change behaviors. Once they&apos;re realized, a patient can start working against them, with the help of the brain&apos;s own neuroplasticity. Essentially, neurons can disconnect and reconnect, or loosen their connections and tighten them, which often manifests in noticeable change.&lt;/p&gt;
&lt;p&gt;&quot;[Psychological] insights can actually begin to change brain chemistry and diffuse compulsions,&quot; he said. &quot;If you address those issues, you can have a positive impact on your life that can change the chemistry of your brain.&quot;&lt;/p&gt;
&lt;p&gt;Smaller said it &quot;creates a new psychological  --  if not neurological  --  structure that can help regulate behavior.&quot;&lt;/p&gt;
&lt;p&gt;Although research on neuroplasticity is relatively young, the concept of &quot;rewiring&quot; the brain is not new.&lt;/p&gt;
&lt;p&gt;In fact, too often, the electrician metaphor has been employed as an excuse for indulging, an explanation for a New Year&apos;s resolution deferred: &quot;I can&apos;t stop eating chocolate, I&apos;m just not wired that way.&quot;&lt;/p&gt;

&lt;hr&gt;
&lt;p&gt;&lt;img src=&quot;http://www.medpagetoday.com/upload/2009/10/30/16717.jpg&quot; mce_src=&quot;http://www.medpagetoday.com/upload/2009/10/30/16717.jpg&quot; alt=&quot;&quot;&gt;&lt;em&gt; is a collaboration between &lt;/em&gt;MedPage Today &lt;em&gt;and&lt;/em&gt; ABC News&lt;em&gt;.&lt;/p&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_279"
                     title="Low-Carb Diet Edges Low Fat Plus Weight-Loss Drug (CME/CE)"
                     score="0.004"
                     href="http://www.medpagetoday.com/PrimaryCare/DietNutrition/tb/18131?impressionId=1265744585390"
                     
      Weight loss was the same and blood pressure control was more effective with a low-carbohydrate diet than a low-fat regimen supplemented by the diet drug orlistat (Xenical, Alli), a randomized trial found.&lt;br&gt;
&lt;br&gt;Among 146 overweight or obese outpatients, both treatment plans led to weight loss of about 10% after 48 weeks, with similar improvements in glycemic and blood lipid measures, according to William S. Yancy Jr., MD, MHS, of Duke University, and colleagues.&lt;br&gt;
&lt;br&gt;But mean systolic and diastolic blood pressure declined by 5.9 and 4.5 mm Hg, respectively, in the low-carb diet compared with a slight increase in patients on the low-fat diet plus orlistat (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 for both measures), the researchers reported in the Jan. 25 issue of &lt;em&gt;Archives of Internal Medicine&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;Both interventions also included small-group sessions with a dietitian every two weeks for the first six months. Yancy and colleagues indicated that participants with the best attendance at these meetings seemed to benefit the most.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;Mean weight loss was 14% to 15% among participants who attended at least 80% of the sessions.&lt;/p&gt;
&lt;p&gt;This latter finding &quot;may indicate the usefulness of these sessions, signify motivated participants, or both,&quot; the researchers wrote.&lt;/p&gt;
&lt;p&gt;&quot;How to identify these select individuals [with high attendance] a priori and how to move more individuals into this category is vital to reversing the obesity epidemic,&quot; they added.&lt;/p&gt;
&lt;p&gt;Yancy and colleagues indicated that the study was the first head-to-head, randomized trial comparing a low-carb diet with a low fat regimen plus orlistat (now readily available over-the-counter).&lt;/p&gt;
&lt;p&gt;Participants were recruited from outpatient clinics attached to the VA Medical Center in Durham. Their mean age was 52 and they had a mean body mass index of 39.3. Only slightly more than one-quarter of patients in each group were women.&lt;/p&gt;
&lt;p&gt;Low-carb dieters could eat as much meat and eggs as they liked, along with up to 112 g of hard cheese, 0.48 L of leafy greens and other low-carbohydrate vegetables, and half as much in other vegetables such as asparagus and broccoli. There was no specific caloric limit.&lt;/p&gt;
&lt;p&gt;Participants assigned to the low-fat diet were told to keep total fat to less than 30% of total caloric content and saturated fat less than 10%.&lt;/p&gt;
&lt;p&gt;Cholesterol intake was to be less than 300 mg/day. Patients in this group were encouraged to reduce total caloric intake by 500 to 1,000 kcal less than the estimated weight-maintenance level. Pocket guides, handouts, and individual assistance were provided to help patients meet these goals.&lt;/p&gt;
&lt;p&gt;Patients in the low-fat group also received orlistat at 120 mg before meals three times daily.&lt;/p&gt;
&lt;p&gt;Mean weight loss with the low-fat diet plus orlistat after 48 weeks was 8.5%, compared with 9.5% in the low-carb diet group (&lt;em&gt;P&lt;/em&gt;=0.60), Yancy and colleagues reported.&lt;/p&gt;
&lt;p&gt;Body weight in kilograms and waist circumference also declined slightly more with the low-carb diet but, again, the difference was not statistically significant.&lt;/p&gt;
&lt;p&gt;Total cholesterol declined by an average of 8.9 mg/dL with the low-fat diet plus orlistat, versus a decrease of 3.8 mg/dL in the low-carb group (&lt;em&gt;P&lt;/em&gt;=0.29). A similar but also nonsignificant difference was seen in LDL cholesterol. Triglyceride levels actually declined more with the low-carb diet but that, too, was not statistically significant.&lt;/p&gt;
&lt;p&gt;A nonsignificant trend was also seen for the low-carb diet to be associated with greater improvements in fasting glucose, fasting insulin, and glycated hemoglobin levels.&lt;/p&gt;
&lt;p&gt;The sole significant difference between outcomes, apart from blood pressure, was in serum urea nitrogen, which increased by a mean of 3.19 mg/dL with the low-carb diet and by 1.23 mg/dL with low fat plus orlistat (&lt;em&gt;P&lt;/em&gt;=0.01).&lt;/p&gt;
&lt;p&gt;Both diets appeared to be successful in terms of adherence, on average. Those on the low-fat diet cut their saturated fat intake by half and total fat by 40%. Participants assigned to the low-carb diet reduced their mean daily carbohydrate intake from 262 g/day at baseline to just 62 g/day at their final evaluation at week 48.&lt;/p&gt;
&lt;p&gt;Total caloric intake declined by 29% in each group from baseline.&lt;/p&gt;
&lt;p&gt;Yancy and colleagues noted that participants were not paid or given food or access to exercise facilities. &quot;Our goal was to design the interventions so that they closely mimicked a weight-loss program that could be instituted in an outpatient clinic,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;But in an accompanying editorial, Robert F. Kushner, MD, of Northwestern University in Chicago, questioned whether either regimen was truly practical in ordinary practice.&lt;/p&gt;
&lt;p&gt;In particular, he pointed to the apparently considerable role of the dietitian-led counseling sessions. Currently, he noted, such sessions &quot;are not a covered benefit by most health plans for the treatment of obesity and most primary care practice offices do not have the resources to conduct group sessions.&quot;&lt;/p&gt;
&lt;p&gt;Kushner also observed that primary care physicians were not directly involved in the treatment plans.&lt;/p&gt;
&lt;p&gt;He suggested that more emphasis should be placed on engaging and empowering primary care physicians in treating obesity.&lt;/p&gt;
&lt;p&gt;&quot;Healthcare reform and training is needed to allow primary care physicians to tackle the obesity crisis,&quot; Kushner wrote.&lt;/p&gt;
&lt;p&gt;One limitation to the study, the authors noted, was that patients were not charged for orlistat. &quot;This could have increased dietary adherence, group session attendance, and/or participant retention compared with the [low-carb diet],&quot; they wrote.&lt;/p&gt;
&lt;p&gt;Another limitation was the lack of blinding in the study, they said.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Funding for the study came from the Department of Veterans Affairs.&lt;/p&gt;&lt;p&gt;Yancy and another study author have received research funding from the Robert C. Atkins Foundation. Atkins developed the low-carbohydrate diet program that bears his name. No other potential conflicts of interest were reported by study authors or Kushner.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_6_356"
                     title="Low-Carb and Mediterranean Diets May Equal Watching Fat Intake"
                     score="-0.005"
                     href="