Researchers discover the brain origins of variation in pathological anxiety

Anxiety News | 27 March 2013

New findings from nonhuman primates suggest that an overactive core circuit in the brain, and its interaction with other specialized circuits, accounts for the variability in symptoms shown by patients with severe anxiety. In a brain-imaging study to be published online today in the Proceedings of the National Academy of Sciences (PNAS), researchers from the University of Wisconsin School of Medicine and Public Health describe work that for the first time provides an understanding of the root causes of clinical variability in anxiety disorders.

Using a well-established nonhuman primate model of childhood anxiety, the scientists identified a core circuit that is chronically over-active in all anxious individuals, regardless of their particular pattern of symptoms. They also identified a set of more specialized circuits that are over- or under-active in individuals prone to particular symptoms, such as chronically high levels of the stress-hormone cortisol.

"These findings provide important new insights into altered brain functioning that explain why people with anxiety have such different symptoms and clinical presentations, and it also gives us new ideas, based on an understanding of altered brain function, for helping people with different types of anxiety,'' says Dr. Ned Kalin, senior author, chair of Psychiatry and director of the HealthEmotions Research Institute.

"There is a large need for new treatment strategies, because our current treatments don't work well for many anxious adults and children who come to us for help."

In the study, key anxiety-related symptoms were measured in 238 young rhesus monkeys using behavioral and hormonal measurement procedures similar to those routinely used to assess extreme shyness in children. Young monkeys are ideally suited for these studies because of their similarities in brain development and social behavior, Kalin noted. Variation in brain activity was quantified in the monkeys using positron emission tomography (PET) imaging, a method that is also used in humans.

Combining behavioral measures of shyness, physiological measures of the stress-hormone cortisol, and brain metabolic imaging, co-lead authors Dr. Alexander Shackman, Andrew Fox, and their collaborators showed that a core neural system marked by elevated activity in the central nucleus of the amygdala was a consistent brain signature shared by young monkeys with chronically high levels of anxiety. This was true despite striking differences across monkeys in the predominance of particular anxiety-related symptoms.

The Wisconsin researchers also showed that young monkeys with particular anxiety profiles, such as high levels of shyness, showed changes in symptom-specific brain circuits. Finally, Shackman, Fox, and colleagues uncovered evidence that the two kinds of brain circuits, one shared by all anxious individuals, the other specific to those with particular symptoms, work together to produce different presentations of pathological anxiety.

The new study builds upon earlier work by the Kalin laboratory demonstrating that activity in the amygdala is strongly shaped by early-life experiences, such as parenting and social interactions. They hypothesize that extreme anxiety stems from problems with the normal maturation of brain systems involved in emotional learning, which suggests that anxious children have difficulty learning to effectively regulate brain anxiety circuits. Taken together, this line of research sets the stage for improved strategies for preventing extreme childhood anxiety from blossoming into full-blown anxiety disorders.

"This means the amygdala is an extremely attractive target for new, broad-spectrum anxiety treatments,'' says Shackman. "The central nucleus of the amygdala is a uniquely malleable substrate for anxiety, one that can help to trigger a wide range of symptoms."

The work also suggests more specific brain targets for different symptom profiles. Such therapies could range from new, more selectively targeted medications to intensive therapies that seek to re-train the amygdala, ranging from conventional cognitive-behavioral therapies to training in mindfulness and other techniques, Shackman noted. To further understand the clinical significance of these observations, the laboratory is conducting a parallel study in young children suffering from anxiety disorders.

Panel backs approval of implants for addiction treatment

Addiction News | 26 March 2013

A four-rod subdermal implant that slowly releases buprenorphine over 6 months should be approved for maintenance treatment of opioid dependence, although more work is needed to determine optimal dosing strategies and how to address the potential risks of the treatment, the majority of a Food and Drug Administration advisory panel recommended.

At a meeting on March 21, the FDA’s Psychopharmacologic Drugs Advisory Committee voted 10-4, with 1 abstention, to recommend approval, based on the efficacy, safety, and risk-benefit profile in opioid-addicted adults treated with the implants, in two phase III placebo-controlled studies. In those studies, the mean proportion of negative urine tests over 24 weeks, the primary endpoint, was significantly higher among those who received the buprenorphine implant, compared with those who had a placebo implant.

The panel agreed the treatment had a beneficial effect on reducing illicit opioid use, but those voting on both sides pointed out that more information on dosing was needed. The product is indicated for patients who are maintained on 12 mg-16 mg of oral buprenorphine a day. But as addiction treatment specialists on the panel pointed out, some patients are maintained on lower oral doses, and there were no data on how to use the product in such patients. The manufacturer, Titan Pharmaceuticals, plans to study that issue further.

The panel also voted 12-2 with 1 abstention, that the company had adequately characterized the safety profile of treatment with the buprenorphine implants, which was associated with the known side effects of the oral formulation in the trials. But there are also the potential complications associated with surgical implantation and removal of the rods every 6 months, as well as the potential for abuse, misuse and diversion, and accidental exposure, which is addressed in a complex risk management program proposed by the manufacturer.

Using similar technology as contraceptive implants, the product consists of four rods, each measuring 26 mm by 2.5 mm and containing 80 mg of the buprenorphine, a partial mu-opioid receptor agonist that has been available in oral formulations since 2002 for the treatment of opioid dependence. The rods are subdermally implanted in the upper arm with a single-use application by a trained health care provider in an office-based surgical procedure with local anesthesia after the patient has been titrated with an oral dose. The rods stay in place for up to 6 months, at which time they are removed and replaced at another site.

"Clearly, the data need to be further assessed and the safety and dosing improved upon," said Dr. Christopher J. Kratochvil, professor of psychiatry and pediatrics, University of Nebraska, Omaha. But he voted in favor of approval, commenting, "This is will at least be an incremental step forward for a disorder that has very tragic consequences."

"Overall, I thought that benefit was shown and there might be a particular subset of patients who respond best to this intervention," said one of the two panelists with expertise on contraceptive implants, Dr. Geri D. Hewitt, an obstetrician-gynecologist at Ohio State University, Columbus, who voted for approval. "I did not see any evidence of significant harm; I do have questions about dosing and which physicians will be willing to place this and ... it’s going to be important to keep track of adverse event reporting," she added.

Voting against approval, Dr.. Laura F. McNicholas of the Center for Studies of Addiction at the University of Pennsylvania, Philadelphia, said she thought the product was approvable, but that approval before a dose-ranging study was conducted would be premature. A major concern she had was running out of sites to implant the rods for patients on long-term treatment, since many of her patients have been taking buprenorphine continuously for years. Many of her patients also are on doses under 12 mg a day, and there was no information on how to dose such patients with the implant, for which there is currently only one dose, she added.

So far, the company has identified four sites on the upper arms as appropriate for implantation and is studying this further.

The two studies enrolled 450 adults (mean age, mid-30s) addicted to an opioid, randomized to treatment with the buprenorphine implant or a placebo implant. The most common drug of abuse was heroin in 52% to 67%, followed by prescription analgesics in 33% to 48%.Over 24 weeks, the mean percentage of opioid-negative urine samples was statistically significantly greater among those who were treated with the buprenorphine implant (about 40% and about 35% among those who received the active drug vs. about 30% and 15%, respectively, among those on the placebo implant.)

About 80% of the patients were adequately treated with four implants, but in some patients, a fifth rod or supplemental treatment with sublingual buprenorphine was needed. Completion rates were lower among those on placebo (31% and 26%, vs. 64% and 66%, respectively). In the two studies, the most common implant site–related adverse events included pruritus, pain, erythema, edema, and hematoma.

The company’s Risk Evaluation and Mitigation Strategy (REMS) includes plans for restricted distribution, a specialty pharmacy only, and a training-certification program for health care providers who implant the rods. (The FDA requires a REMS for a drug when it determines that a risk management strategies beyond the label are needed to ensure the benefits of a drug outweigh its risks.) Both the panel and the FDA reviewers said the REMS needs to be improved.

When asked about the panel’s recommendation, Dr. Robert L DuPont said in an interview that it is a major development in medication-assisted treatment of opiate dependence in light of problems with diversion and nonmedical use of buprenorphine. "This novel dosing strategy removes the risk of diversion in a large population of drug abusing patients that poses a high risk of diversion and misuse," said Dr. DuPont, the first director of the National Institute on Drug Abuse.

"The development of abuse-resistant formulations of controlled substances is one of the best new ideas to turn back the major epidemic of prescription drug abuse."

If approved, the panel recommended that other potential problems with the device should be monitored closely, including removal of implants by nonmedical personnel for diversion (which was not seen in the studies) and the risk of long-term exposure to the components if they are not removed. The panel urged study of whether implants can be inserted in previous implant sites.

Buprenorphine can be administered in an office setting as opposed to a methadone clinic. The currently marketed buprenorphine products are Subutex and Suboxone (buprenorphine with naloxone), both available in generic formulations; and a sublingual formulation approved in 2010. In 2012, 10.7 million prescriptions were dispensed for buprenorphine products for an estimated 1 million patients, mostly the buprenorphine/naloxone combination, according to the FDA. Between January 2003 and December 2012, an estimated 40 million buprenorphine prescriptions were written. The top three categories of prescribers were general practitioners/family physicians/doctors of osteopathy (one category), psychiatrists, and internists.

If approved, the manufacturer plans to market it as Probuphine. The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist might be given a waiver, but not at this meeting.

Alterations in brain activity in children at risk of schizophrenia predate onset of symptoms

Schizophrenia News | 26 March 2013

Brain scans of children at risk of schizophrenia reveal neural circuitry that’s hyperactivated by tasks that peers with no family history of the illness seem to handle with ease.

Because these differences in brain functioning appear before neuropsychiatric symptoms such as trouble focusing, paranoid beliefs, or hallucinations, the scientists believe that the finding could point to early warning signs or “vulnerability markers” for schizophrenia.

“The downside is saying that anyone with a first degree relative with schizophrenia is doomed. Instead, we want to use our findings to identify those individuals with differences in brain function that indicate they are particularly vulnerable, so we can intervene to minimize that risk,” says senior study author Aysenil Belger, associate professor of psychiatry at the University of North Carolina School of Medicine.

The new study, published online in Psychiatry Research: Neuroimaging, is one of the first to look for alterations in brain activity associated with mental illness in individuals as young as nine years of age.

Individuals who have a first-degree family member with schizophrenia have an 8-fold to 12-fold increased risk of developing the disease. However, there is no way of knowing for certain who will become schizophrenic until symptoms arise and a diagnosis is reached.

Some of the earliest signs of schizophrenia are a decline in verbal memory, IQ, and other mental functions, which researchers believe stem from an inefficiency in cortical processing—the brain’s waning ability to tackle complex tasks.

In this study, Belger and her colleagues sought to identify what if any functional changes occur in the brains of adolescents at high risk of developing schizophrenia.

She performed functional magnetic resonance imaging (fMRI) on 42 children and adolescents ages 9 to 18, half of which had relatives with schizophrenia and half of which did not.

Study participants each spent an hour and a half playing a game where they had to identify a specific image—a simple circle—out of a lineup of emotionally evocative images, such as cute or scary animals. At the same time, the MRI machine scanned for changes in brain activity associated with each target detection task.

Belger found that the circuitry involved in emotion and higher order decision-making was hyperactivated in individuals with a family history of schizophrenia, suggesting that the task was stressing out these areas of the brain in the study subjects.

“This finding shows that these regions are not activating normally,” she says. “We think that this hyperactivation eventually damages these specific areas in the brain to the point that they become hypoactivated in patients, meaning that when the brain is asked to go into high gear it no longer can.”

Belger is currently exploring what kind of role stress plays in the changing mental capacity of adolescents at high risk of developing schizophrenia. Though only a fraction of these individuals will be diagnosed with schizophrenia, Belger thinks it is important to pinpoint the most vulnerable people early to explore interventions that may stave off the mental illness.

“It may be as simple as understanding that people are different in how they cope with stress,” says Belger. “Teaching strategies to handle stress could make these individuals less vulnerable to not just schizophrenia but also other neuropsychiatric disorders.”

The National Institute of Mental Health and the National Institute of Child Health and Human Development supported the study, to which additional researchers from UNC and Duke University contributed.

Brain alterations evident in bipolar II disorder

Bipolar Disorder News | 26 March 2013

Results from a combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) study show that patients with bipolar II disorder (BD II) have structural brain alterations compared with mentally healthy individuals.

However, these alterations are less pronounced than those previously observed in patients with BD I, "confirming reports that brain structure of [BD II] patients is less severely affected than that of [BD I] patients," say Elisa Ambrosi (Sapienza University, Rome, Italy) and team.

The findings come from a study of 20 euthymic BD II patients, aged between 18 and 65 years (mean age 41.9 years), and 21 mentally healthy controls.

There were no significant differences between the groups regarding age, gender and handedness, but controls had received significantly more years of education than BD II patients, at a mean of 16 vs 13 years.

All of the participants underwent magnetic resonance imaging of the brain, with VBM and DTI used to assess between-group differences in gray and white matter volume.

The team found that, compared with controls, BD II patients showed localized gray matter volume reductions mainly in the right middle frontal gyrus (Brodmann area 8) and the right superior temporal gyrus (Brodmann area 22). There were no brain regions in which BD II patients showed greater gray matter volume than controls.

Regarding white matter, BD II patients showed significantly lower fractional anisotropy values than controls in all major white matter tracts studied, including cortico-cortical association tracts (ie, the uncinate, inferior fronto-occipital, inferior longitudinal, and superior longitudinal fasciculi), interhemispheric tracts, and limbic tracts.

The researchers note that education level did not correlate with any VBM or DTI measure.

Ambrosi and team conclude in the Journal of Affective Disorders: "Our preliminary combined VBM-DTI study found structural brain differences between [BD II] patients and HCs [healthy controls]; these differences are less pronounced than previously described differences between [BD I] patients and HCs.

"Further studies should seek to address some still unresolved issues, i.e., stability of alterations over time and their possible phase-relatedness, and their correlation with clinical and neuropsychological measures."

UNC study shows how two brain areas interact to trigger divergent emotional behaviors

Anxiety News | 25 March 2013

New research from the University of North Carolina School of Medicine for the first time explains exactly how two brain regions interact to promote emotionally motivated behaviors associated with anxiety and reward. 

The findings could lead to new mental health therapies for disorders such as addiction, anxiety, and depression. A report of the research was published online by the journal, Nature, on March 20, 2013. 

Located deep in the brain’s temporal lobe are tightly packed clusters of brain cells in the almond shaped amygdala that are important for processing memory and emotion. When animals or people are in stressful situations, neurons in an extended portion of the amygdala called the bed nucleus of the stria terminalis, or BNST, become hyperactive. 

But, almost paradoxically, neurons in the BNST, which modulate fear and anxiety, reach into a portion of the midbrain that’s involved in behavioral responses to reward, the ventral tegmental area, or VTA.

“For many years it’s been known that dopamine neurons in the VTA are involved in reward processing and motivation. For example, they’re activated during exposure to drugs of abuse and naturally rewarding experiences,” says study senior author Garret Stuber, PhD, assistant professor in the departments of Psychiatry and Cell Biology and Physiology, and the UNC Neuroscience Center.  “On the one hand, you have this area of the brain – the BNST – that’s associated with aversion and anxiety, but it’s in direct communication with a brain reward center. We wanted to figure out exactly how these two brain regions interact to promote different types of behavioral responses related to anxiety and reward.”

In the past, researchers have tried to get a glimpse into the inner workings of the brain using electrical stimulation or drugs, but those techniques couldn’t quickly and specifically change only one type of cell or one type of connection. But optogenetics, a technique that emerged about seven years ago, can.

In the technique, scientists transfer light-sensitive proteins called “opsins” – derived from algae or bacteria that need light to grow – into the mammalian brain cells they wish to study. Then they shine laser beams onto the genetically manipulated brain cells, either exciting or blocking their activity with millisecond precision.

First, Stuber and colleagues used optogenetics for “photo-tagging,” to optically identify different types of neurons in vivo. This enabled them to identify a neuron in the BNST that’s projecting into the VTA. “So we know the neuron is directly interfacing with a reward-related brain region,” Stuber says.

They then exposed animals (mice) to a mild aversive stimulus, a carefully controlled but anxiety-provoking foot shock delivered repeatedly and unpredictably.  The BNST neurons projecting into the VTA showed changes in their firing rate, “But some cells would increase their activity and other would suppress their firing,” Stuber says, adding that it suggested there are functionally distinct populations of neurons within the BNST that are projecting to the VTA, thus highlighting the complexity of this neural circuit.

Stuber and his team then repeated the experiment, but this time optically identified BNST neurons that project to the VTA as either excitatory or inhibitory cells, by integrating the approach they developed with the use of transgenic animals that allows for precise targeting of distinct neuronal cell types. The glutamate (excitatory) neurons were the cell population that increased their activity in response to the foot shocks.  And the GABAergic (inhibitory) cells showed activity suppression during foot shock. 

Finally, the researchers found that stimulating either of these brain cell pathways had opposing behavioral consequences. The glutamate neurons provoked an aversive, avoidance behavioral response and promoted anxiety-like behavior in the mice. In contrast, when Stuber’s team activated the GABAergic pathway projections from the BNST into the VTA, the animals showed reward-associated behaviors and less anxiety. They preferred that stimulation and would spend more time in the area of the cage where they had received it. 

“If you activated the GABA cells, they showed less anxiety. And when we exposed them to foot shock and at the same time activated this GABAergic pathway, it actually reduced the anxiety-associated behavioral consequences of that otherwise “aversive” stimulation,” Stuber says.

“Because these cells are functionally and genetically distinct from each other, our findings also point to new potential targets for therapeutic interventions in neuropsychiatric disorders associated with alterations in motivated states such as addiction.

Along with Stuber, UNC study co-authors from the department of psychiatry are Joshua H. Jennings, Dennis R. Sparta, Alice M. Stamatakis and Randall L. Ung.  Other co-authors on this study include Kristen E. Pleil  and Thomas L. Kash who are affiliated with  the department of pharmacology, and the Bowles Center for Alcohol Studies. Support for the study comes from the National Institutes of Health, the Whitehall Foundation, and the Foundation of Hope.

It’s All in the Nerves: How to Really Treat Depression

Depression News | 25 March 2013

Exercise, Prozac and electroconvulsive therapy (ECT) may ultimately relieve depression in the same way.

That’s what the latest research, conducted on mice, suggests, and the scientists are encouraged that similar processes are at work in the human brain as well. According to the findings, published in the journals Cell Stem Cell and Molecular Psychiatry, all of these therapies can spur the growth of brain cells. And it seems that such neurogenesis, which perhaps results from changes in levels of brain chemicals like serotonin, can lift the symptoms of depression.

Since the mid-1990s, researchers have been piecing together a theory of depression that accounts for the seemingly disparate triggers of the mental illness, as well as the variety of treatments that seem to counteract the negative mood.

And so far, this is what they believe: extreme or uncontrollable stress, particularly early in life, can lead to excessive release of the neurotransmitter glutamate in the brain.  At these high levels, glutamate can damage or even kill certain cells in the hippocampus, a region known for its role in memory.  This can lead to a thinning of the neural network in this area, which contributes to depression for reasons that are not yet clear. But antidepressant treatments all seem to promote the birth of new brain cells in that part of the brain.

Moreover, “It’s not just growth of new nerve cells [in this region],” says Bruce McEwen, professor of neuroscience at Rockefeller University, ”There’s also plasticity of nerve cells all over the brain  that is ongoing and can be facilitated or blocked.”  These changes may start in the hippocampus, where new cells can be born, but older cells can be revitalized elsewhere as well, perhaps even changing the circuit of nerve activity that keeps people stuck in depressive thoughts and feelings.

Now, Hongjun Song, professor of neurology and neuroscience at Johns Hopkins University, documents how disparate treatments, from exercise to antidepressants that manipulate serotonin levels, and even electrical stimulation of certain brain regions, can ultimately trigger this nerve growth that fights depression.

The brain must maintain a delicate balance, with complex chains of signals keeping various opposing processes in check.  One protein that stymies the growth of brain cells, sFRP3, is useful in controlling cell growth from getting out of hand, but could be harmful if it hampers necessary growth. Working with mice, Song and his colleagues showed that antidepressant medications, ECT and exercise all affect levels of sFRP3.

“If you treat with different classes of antidepressants or ECT, they all lead to changes in expression of sFRP3,” says Song, who studied Prozac (fluoxetine), a selective serotonin reuptake inhibitor (SSRI) and imipramine, an antidepressant in another class of drugs called tricyclics, which regulate multiple neurotransmitters.  The research showed that these drugs reduced levels of sFRP3 levels in the hippocampus, which allowed new cells and connections to grow.

To further confirm the effect of sFRP3 on depression, Song and his colleagues also genetically engineered mice without the sFRP3 protein; these animals were less likely to show depressive responses when they were forced to swim until exhaustion, an indication that they were less prone to experiencing the negative mood state.

The research also found that in human patients, genes associated with the protein affected how long it took depressed people to respond to medication. Taken together, the latest data suggests that presence of elevated levels of sFRP3 protein may increase vulnerability to depression by preventing new nerve cells from growing in the hippocampal region. Similarly, mice given ECT, and those that exercised regularly, also showed lower levels of sFRP3.

So how do things as different as ECT, drugs and exercise change the same protein? They all affected a single type of cell in the hippocampus, known as granule cells.  “What matters is that you want to activate [these] granule cells,” says Song. “If the animals do running, that leads to firing of those neurons,” he says, explaining that all of the other treatments did so as well.

Further studies are needed to confirm whether consistently high levels of the protein increase the likelihood of depression in human patients, but if that’s the case, then activating granule cells, by way of suppressing the release of sFRP3, might be a promising new way of treating depression. So far, “no drugs are known [to affect it directly],” says Song, “The next step is trying to find an approach where we can modulate the function of sFRP3 as an antidepressant.”

Autism Research in Psychological Science

Autism Spectrum Disorders News | 22 March 2013

April 2 is World Autism Awareness Day, recognized by the United Nations General Assembly for the purpose of improving the lives of people living with autism. According to the organization Autism Speaks, autism affects 1 in 88 children; however, scientists are still working to understand the causes of autism-spectrum conditions (ASC) and develop evidence-based interventions.

An upcoming article in Psychological Science adds another piece of understanding to the autism puzzle. Richard Cook and his colleagues at City University London noted that in the past, some studies have concluded that persons with ASC have trouble identifying faces and facial emotions, but other studies have not found evidence of such deficiencies.

Cook’s team drew on these gaps in scientists’ understanding of how people with ASC process faces to test the hypothesis that a personality trait called alexithymia — that is, difficulty identifying and describing emotions — is the real cause of the emotional symptoms associated with autism. About 10 percent of the general population experiences alexithymia, and more than half of people with autism may experience severe alexithymia. However, autism and alexithymia occur independently of each other.

In two experiments, Cook and his colleagues used morph continua (photos that blended the facial features and expressions of two individuals) to test participants’ ability to identify the emotional content of facial expressions, individual faces, and variation in facial expressions. Experiments were performed on two groups — one that consisted of 16 participants diagnosed with ASC, and a second that consisted of 16 participants who did not meet the criteria for ASC. Each group included five alexithymic individuals.

Analysis of the results showed that alexithymia but not ASC predicted an impaired ability to recognize emotional expressions. Furthermore, neither alexthymia nor autism predicted participants’ ability to identify individuals based on their facial features or participants’ ability to detect physical differences between facial expressions — axethymia instead appears to impair individuals interpretation of emotional content.

Similar studies have shown that empathic brain activity and gaze fixations to emotional social stimui are also better predicted by alexthymia than they are by ASC. Based on their findings, Cook and his team suggest that it may be appropriate to rethink “the characterization of autism as a disorder with emotional symptoms.” The study also highlights the importance of balancing the number of alexithymic and non-alexithymic individuals used in experiments designed to study autism so that symptoms of alexithymia are not mistakenly attributed to autism. The study is a reminder that scientists have a long way to go toward understanding autism, but every piece of the puzzle is a step toward improving the lives of those affected by ASC.

Does Winning Mean You Will Live Longer Than Those You Beat?

Other News | 22 March 2013

Research has long linked high socioeconomic status with better health and lower mortality. But what’s remained unclear is whether this association has more to do with access to resources or the glow of high social status relative to others, known as “relative deprivation.”

To tease apart these factors, a team of investigators led by Bruce Link, PhD, at Columbia University’s Mailman School of Public Health, studied Baseball Hall of Fame inductees, Emmy Award winners, and former Presidents and Vice Presidents, comparing each to nominated losers in the same competition or election. The result: There were no consistent advantages for winners. The association between winning and longevity is sometimes positive, sometimes negative, and sometimes nonexistent, though the specifics are revealing. Overall, the results suggest that access to resources and opportunity is more important than relative status.  

Findings are published online in the American Sociological Review.

Dr. Link and colleagues at the University of British Columbia and RAND found the following effects of winning vs. losing in the three groups:

Emmy-winning actors enjoyed 2.7 more years of life than nominees who did not snag the trophy. Though Academy Award-winning screenwriters were, mysteriously, at a three-year disadvantage.

Baseball Hall-of-Famers enjoyed no advantage in longevity over non-inducted nominees.

Presidents and Vice Presidents lose, on average, 5.3 years from their lives compared to the candidates they bested. While some of this is due to the impact of assassination, the disadvantage persists even when assassination is taken out of the equation.

"The relative deprivation theory would predict that losers would consistently be at a disadvantage for health and longevity compared to winners, but this is not what we see," says Dr. Link, a professor of Epidemiology and Sociomedical Sciences at the Mailman School.

A more likely explanation, he notes, is that the advantages and disadvantages of winning depend on the mix of opportunities and stresses that they bring. Winning an Emmy often leads to significant career opportunities that might not have been otherwise available. (The paper quotes actor John Larroquette saying, "There's no doubt that having an Emmy preceeds you through the door.") On the other hand, Baseball Hall of Fame induction occurs after playing careers are over and therefore has little bearing on career opportunities and earnings.

As for presidential and vice presidential candidates, life circumstances do change for members of this elite club, but winning also brings significant risks: assassination threats and extreme stress from two of the world's most demanding jobs. The 15 men who led our country during the 20th century but died by the year 2008 lived an average of 1.9 years less than the average American male of the same age.

"Our findings provide an important correction to an overemphasis on relative deprivation as an explanation of health inequalities," said Dr. Link. "Relative deprivation likely plays some role in health inequalities, but it is not as important as the life circumstances and opportunities that result from one's socioeconomic position."

Sleep Study Reveals How The Adolescent Brain Makes The Transition to Mature Thinking

Insomnia News | 22 March 2013

A new study conducted by monitoring the brain waves of sleeping adolescents has found that remarkable changes occur in the brain as it prunes away neuronal connections and makes the major transition from childhood to adulthood.

“We’ve provided the first long-term, longitudinal description of developmental changes that take place in the brains of youngsters as they sleep,” said Irwin Feinberg, professor emeritus of psychiatry and behavioral sciences and director of the UC Davis Sleep Laboratory. “Our outcome confirms that the brain goes through a remarkable amount of reorganization during puberty that is necessary for complex thinking.”

The research, published in the February 15 issue of American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, also confirms that electroencephalogram, or EEG, is a powerful tool for tracking brain changes during different phases of life, and that it could potentially be used to help diagnose age-related mental illnesses. It is the final component in a three-part series of studies carried out over 10 years and involving more than 3,500 all-night EEG recordings. The data provide an overall picture of the brain’s electrical behavior during the first two decades of life.

Feinberg explained that scientists have generally assumed that a vast number of synapses are needed early in life to recover from injury and adapt to changing environments. These multiple connections, however, impair the efficient problem solving and logical thinking required later in life. His study is the first to show how this shift can be detected by measuring the brain’s electrical activity in the same children over the course of time.

Two earlier studies by Feinberg and his colleagues showed that EEG fluctuations during the deepest (delta or slow wave) phase of sleep, when the brain is most recuperative, consistently declined for 9- to 18-year-olds. The most rapid decline occurred between the ages of 12 and 16-1/2. This led the team to conclude that the streamlining of brain activity — or “neuronal pruning" — required for adult cognition occurs together with the timing of reproductive maturity.

Questions remained, though, about electrical activity patterns in the brains of younger children.

For the current study, Feinberg and his research team monitored 28 healthy, sleeping children between the ages of 6 and 10 for two nights every six months. The new findings show that synaptic density in the cerebral cortex reaches its peak at age 8 and then begins a slow decline. The recent findings also confirm that the period of greatest and most accelerated decline occurs between the ages of 12 and 16-1/2 years, at which point the drop markedly slows.

“Discovering that such extensive neuronal remodeling occurs within this 4-1/2 year timeframe during late adolescence and the early teen years confirms our view that the sleep EEG indexes a crucial aspect of the timing of brain development,” said Feinberg.

The latest study also confirms that EEG sleep analysis is a powerful approach for evaluating adolescent brain maturation, according to Feinberg. Besides being a relatively simple, accessible technology for measuring the brain’s electrical activity, it is more accurate than more cumbersome and expensive options.

“Structural MRI, for instance, has not been able to identify the adolescent accelerations and decelerations that are easily and reliably captured by sleep EEG,” said Feinberg. “We hope our data can aid the search for the unknown genetic and hormonal biomarkers that drive those fluctuations. Our data also provide a baseline for seeking errors in brain development that signify the onset of diseases such as schizophrenia, which typically first become apparent during adolescence. Once these underlying processes have been identified, it may become possible to influence adolescent brain changes in ways that promote normal development and correct emerging abnormalities.”

Feinberg’s study, which was funded by the U.S. Public Health Service (grant R01MH062521), was co-authored by Ian Campbell, a project scientist with the UC Davis Department of Psychiatry and Behavioral Sciences.

Discovery Could Yield Treatments For Cocaine Addicts

Addiction News | 20 March 2013

Scientists have found a molecular chain reaction in the brain triggered by cocaine, and say that interrupting this process could provide treatment for addiction. Researchers say cocaine alters the nucleus accumbens, the brain’s pleasure center that responds to stimuli such as food, sex, and drugs.

“Understanding what happens molecularly to this brain region during long-term exposure to drugs might give us insight into how addiction occurs,” says A. J. Robison, assistant professor in the department of physiology and the neuroscience program at Michigan State University.

The researchers found that cocaine causes cells in the nucleus accumbens to boost production of two proteins, one associated with addiction and the other related to learning. The proteins have a reciprocal relationship—they increase each other’s production and stability in the cells—so the result is a snowball effect that Robison calls a feed-forward loop.

In their research published in the Journal of Neuroscience, Robison and colleagues demonstrated that loop’s essential role in cocaine responses by manipulating the process in rodents.

They found that raising production of the protein linked to addiction made animals behave as if they were exposed to cocaine even when they weren’t. They also were able to break the loop, disrupting rodents’ response to cocaine by preventing the function of the learning protein.

“At every level that we study, interrupting this loop disrupts the process that seems to occur with long-term exposure to drugs,” says Robison.

Robison says the study also found signs of the same feed-forward loop in the brains of people who died while addicted to cocaine.

“The increased production of these proteins that we found in the animals exposed to drugs was exactly paralleled in a population of human cocaine addicts,” he says. “That makes us believe that the further experiments and manipulations we did in the animals are directly relevant to humans.”

Robison says the growing understanding of addiction at the molecular level could help pave the way for new treatments for addicts.

“This sort of molecular pathway could be interrupted using genetic medicine, which is what we did with the mice,” he says. “Many researchers think that is the future of medicine.”