New Studies Examine the Many Facets of Depression

By KATHLEEN DOHENY Psych Central News
Reviewed by John M. Grohol, Psy.D. on November 18, 201


Treatments for depression have improved greatly over the years, yet there are still many patients not helped by traditional offerings of medications and talk therapy.

”Roughly 20 to 40 percent of people with depression aren’t helped by existing therapies,” said Robert Greene, M.D., Ph.D., of the University of Texas Southwestern Medical School in Dallas.  On Monday, he moderated a news conference at the annual meeting of the Society of Neuroscience in San Diego to update research on new options under study.

Among the promising research is new data on:

  • How being stressed out may play a role in depression;
  • How the immune system may play a role in depression;
  • The role of a specific molecule, Cdk5, in nerve cell signaling and how the information might be used for an antidepressant effect;
  • The role of a small protein known as p11 and how it affects antidepressant-like  responses.

To the first of these, Herwig Baier, Ph.D., a researcher at the University of California San Francisco, said, ”An inability to cope with stress may play a role in depression.” He found in a study that zebra fish who have a mutation in a receptor important for stress management displayed abnormal behavior similar to depression. Normally social fish, the zebra fish stopped swimming and hid in the corner of their tanks when isolated from others.

But when these fish were given fluoxetine (Prozac), the behavior disappeared, he found. Studying the fish makes sense, Baier says, as the ”stress axis” in this fish and humans is identical.

The zebra fish’s mutation is in the gene known as the glucocorticoid receptor (GR) gene, and one of its jobs is to ”dial down” the secretion of stress hormones from the brain. Either too much or too little GR activity has been linked with depression.

If the fish story holds true for people, Baier said, new strategies for depression could be developed that don’t block GR activity but activate it to just the right amount so mood is not depressed.

The immune system could also play a role in depression, said Simon Sydserff, PHD, a senior research scientist at BrainCells, Inc., a drug development company in San Diego involved in stem cell technology to develop CNS treatments.

Here’s how:  When you get sick, the immune system hormone IL6 or interleukin 6, carries ”sickness” signals to the brain. When Sydserff activated the immune system of mice to mimic sickness, they displayed behavior representing depression.

“Patients who are depressed who are medically healthy and also those who are medically ill, have high levels of immune system signaling cytokines such as IL6,” he said.

“Interferon alpha, a cancer treatment, increases IL-6 and has also been linked to major depression,” he said. If the research bears out, he said, ”blocking IL-6 may prevent or reverse depression,” offering another option.

He conducted the research, supported by AstraZeneca Pharmaceuticals, while on staff there.

In  another study, James Bibb, Ph.D., of the University of Texas Southwestern Medical Center, Dallas, found that mice lacking a molecule known as Cdk5 like mice given an antidepressant: They were more active, one marker of effective antidepressant action. Without the molecule, the wave of a signaling molecule known as cyclic AMP doesn’t stop as it typically does, and this was linked with antidepressant-like responses. Learning how to block this molecule in the future could provide more options, he said.

Meanwhile, figuring out why an antidepressant can take a while to ”kick in” is the focus of another study. Jennifer Warner-Schmidt, Ph.D., a researcher at The Rockefeller University in New York, zeroed in on a regulator of antidepressant responses known as p11.  It’s a small protein expressed in depression-related brain regions.

She found in animal studies that over-expression of p11 results in an antidepressant effect and that another key regulator, brain-derived neurotrophic factor (BDNF) is required for the serotonin-induced increase in the p11.

”Understanding better the role of p11 in antidepressant response could lead to faster acting antidepressants with fewer side effects,” she said.

SOURCE: Society for Neuroscience.

Virtual Environments Aid Stroke Rehab

By RICK NAUERT PHD Senior News Editor
Reviewed by John M. Grohol, Psy.D. on November 17, 2010


An innovative rehabilitation approach uses virtual environments to simulate functional tasks, allowing repetitive exercise training for stroke victims.

In a new study, Sergei V. Adamovich, Ph.D., and colleagues at the New Jersey Institute of Technology used interactive video game-based therapy to improve hand and arm function among individuals who had suffered a stroke.

“In virtual environments, individuals with arm and hand impairment practiced tasks such as reaching and touching virtual objects. They took a cup from a shelf and put it on a table, hammered a nail, and even played a virtual piano,” Adamovich said.

Even years after a stroke occurs, people with disabled limbs still sometimes show improvement with therapy. Though recent studies have shown recovery is possible, researchers aim to further improve the speed and fluidity of motor control.

In this study, 24 participants who had a stroke at least six months prior to therapy practiced with the video game for about 22 hours over a two-week period. With the aid of a robotic arm, individuals attempted increasingly difficult tasks. Adamovich and his colleagues observed that the volunteers moved their hands faster over the course of the tests.

The researchers also examined whether therapy changed the participants’ brains to improve motor functions. In ongoing trials, the authors used transcranial magnetic stimulation and functional Magnetic Resonance Imaging (fMRI) to map connections in the volunteers’ brains as they underwent rehabilitation.

“Our preliminary data suggest that, indeed, robot-assisted training in virtual reality may be beneficial for functional recovery after chronic stroke,” Adamovich said.

“Furthermore, our data imply that this recovery may be particularly due to increased functional connections between different brain regions.”

Source: Society for Neuroscience

Binge Drinkers May Risk Mood Disorders as Adults

By RICK NAUERT PHD Senior News Editor
Reviewed by John M. Grohol, Psy.D. on November 16, 2010

PRESS ASSOCIATION Photo.
PRESS ASSOCIATION Photo.

A new study on rats suggests binge-drinking teenagers may be putting themselves at higher risk in adulthood for common mental disorders such as anxiety and depression.

Loyola University (Chicago) Health System researchers found that exposing adolescent rats to binge amounts of alcohol permanently altered the system that produces hormones in response to stress.

This disruption in stress hormones “might lead to behavioral and/or mood disorders in adulthood,” researchers reported.

Senior author Toni Pak, Ph.D., and colleagues reported their findings at the annual meeting of the Society for Neuroscience in San Diego.

While results from animal studies don’t directly translate to people, the findings do suggest a mechanism by which teenage binge drinking could cause mental health problems in adulthood, Pak said.

“Exposing young people to alcohol could permanently disrupt normal connections in the brain that need to be made to ensure healthy adult brain function,” Pak said.

Binge drinking is defined as a woman having at least four drinks or a man having at least five drinks on one occasion. Heavy binge drinkers can consume 10 to 15 drinks. Binge drinking typically begins around age 13 and peaks between 18 and 22, before gradually decreasing.

Thirty-six percent of youths ages 18 to 20 reported at least one binge-drinking episode during the past 30 days, according to the federal Substance Abuse and Mental Health Services Administration.

The Loyola study examined the long-term effects of alcohol on the production of the stress hormone corticosterone in rats. The equivalent stress hormone in humans is cortisol.

Humans and rats produce stress hormones in response to physical or psychological stress. For example, in a “fight-or-flight” situation, a jolt of cortisol provides a burst of energy and a lower sensitivity to pain, while suppressing functions that aren’t immediately needed, such as digestion.

However, chronic exposure to cortisol and other stress hormones has been linked to depression, cardiovascular disease and other problems.

In the study, researchers exposed adolescent rats to an 8-day binge drinking pattern: three days of alcohol binging, two days off, then three more days of binging.

On binge days, rats were injected with enough alcohol to raise their blood alcohol concentration to between 0.15 percent and 0.2 percent. (In humans such concentrations would be roughly 2 to 2.5 times higher than the 0.08 legal limit for driving.) A control group of rats received injections of saline.

One month later, when the rats were young adults, they were exposed to one of three regimens: saline injections, a one-time alcohol injection or a binge-pattern of alcohol exposure. Alcohol is a form of stress, so not surprisingly, the animals that had either a one-time or binge alcohol exposure produced more of the corticosterone stress hormone.

A more significant finding is that among rats that had received alcohol during adolescence, there was a significantly larger spike in corticosterone when they received alcohol during adulthood. These rats also had a lower base level of corticosterone than rats that had remained sober during adolescence.

These findings suggest that alcohol exposure during puberty permanently alters the system by which the brain triggers the body to produce stress hormones.

Source: Loyola University Health System

Alcohol Damages Much More Than The Liver

alcohol.jpg
alcohol.jpg

Alcohol does much more harm to the body than just damaging the liver. Drinking also can weaken the immune system, slow healing, impair bone formation, increase the risk of HIV transmission and hinder recovery from burns, trauma, bleeding and surgery.

Researchers will release the latest findings on such negative effects of alcohol during a meeting Nov. 19 of the Alcohol and Immunology Research Interest Group at Loyola University Medical Center.

At Loyola, about 50 faculty members, technicians, post-doctoral fellows and students are conducting alcohol research. Studies at Loyola and other centers could lead to therapies to boost the immune system or otherwise minimize the effects of alcohol, said Elizabeth J. Kovacs, PhD, director of Loyola’s Alcohol Research Program and associate director of Loyola’s Burn & Shock Trauma Institute.

“Of course, the best way to prevent the damaging effects of alcohol is to not drink in the first place,” Kovacs said. “But it is very difficult to get people to do this.”

Sessions at the conference include Alcohol and Infection, Alcohol and Oxidative Stress and Alcohol and Organ Inflammation. Findings will be presented by researchers from centers around the country, including Loyola, Cleveland Clinic, University of Iowa, University of Colorado, University of Massachusetts, Mississippi State University, Chicago State University and the National Institute on Alcohol Abuse and Alcoholism (NIAAA).

The conference is supported by Loyola’s Alcohol Research Program and Department of Surgery at Loyola University Chicago Stritch School of Medicine, the Society for Leukocyte Biology and the NIAAA

Technorati Tags: ,,

Brain Scan Can Predict Therapy Response for Anxious Kids

By RICK NAUERT PHD Senior News Editor
Reviewed by John M. Grohol, Psy.D. on November 15, 2010


Experts say a brain scan can predict which kids with anxiety disorders will respond to one form of psychotherapy. As a consequence, Georgetown University neuroscientists say the use of psychiatric medication is not necessary for certain children.

Their study, presented at the annual meeting of the Society for Neuroscience in San Diego, utilized functional Magentic Resonance Imaging (fMRI) to map regions of brain activity. The results showed that children and adolescents, ages 8 to 16, who show fear when looking at happy faces on a screen were those who had least success with an eight-week course of cognitive-behavioral therapy.

Conversely, children who showed fear while looking at fearful faces benefitted from the treatment, the researchers found.

“Anxiety and fear are intrinsically linked, so how the brain’s fear center responds would naturally affect how anxiety disorders manifest,” said the study’s lead author, Steve Rich, a fourth year medical student.

“Indeed, the impact on their responses to therapy was impressive,” he said.

“Past studies have shown that many people react to fearful faces with fear themselves, but our most robust finding indicated that some anxiety disorder patients have more anxiety towards happy faces than fearful ones, and those patients were the least likely to respond to cognitive-behavioral therapy.”

The study enrolled 13 boys and 10 girls in this study, all of whom had been diagnosed with pediatric anxiety disorder.

While inside the fMRI machine, the participants were shown pictures of faces that expressed certain emotions strongly.

“The questions we were trying to answer were: What emotions make people afraid when they witness them on others’ faces, and does that pattern predict response to talk therapy,” Rich says.

An fMRI records changes in blood flow in the brain, thus showing levels of activity. In this study, the researchers zeroed in on the amygdala, a brain structure involved in fear responses. 

They then correlated the differing responses they saw in the amygdala with outcomes from an eight-week course in cognitive-behavioral therapy.

The researchers found a significant correlation, indicating that pre-treatment fMRI can be used to select patients who likely do well with psychotherapy alone, and those that may require other therapy, such as medication.

Rich said that one explanation for the results is that those patients who have greater anxiety towards happy faces than towards fearful ones have a subtly different disorder, one that is very similar but cannot be treated by cognitive-behavioral therapy.

“In this subset of patients, that support may actually elicit even more anxiety, thus alienating them from the therapist,” he said.

“Further study is required to determine whether this is indeed a unique disease subtype, or whether a modified approach to cognitive-behavioral therapy that requires the therapist to stay completely neutral could make therapy more effective for these patients.”

Rich and his co-authors do not expect that every pediatric anxiety disorder patient should receive an fMRI diagnosis.

“fMRI is expensive, and this study does not by any means suggest that it should be used as a universal screening tool,” he said.

“Even so, once the field develops further, our results suggest that neuroimaging studies like fMRI may be able to help us understand why a given patient might not be responding to the first-line treatment. In other words, when routine care is not enough, we can focus on the nuances of the individual.”

Source: Georgetown University Medical Center