Research May Yield New Drug Targets for Memory, Anxiety Disorders

By TRACI PEDERSEN Associate News Editor
Reviewed by John M. Grohol, Psy.D. on January 10, 2011


A new drug target for anxiety disorders — and particularly post-traumatic stress disorder (PTSD) — is now possible due to a recent unexpected discovery by UCLA scientists.  Their research has honed in on neuronal gap junctions — channels in which electrical communication occurs between inhibitory neurons. 

The discovery also holds promise for Alzheimer’s disease and other memory-related disorders.

“The brain has many processes we have not yet explored,” said UCLA Professor of Psychology Dr. Michael Fanselow. ”Understanding them and how they normally work can open up new approaches that may help in very prevalent and debilitating diseases, such as anxiety disorders and memory disorders.”

Gap junctions form where inhibitory neurons touch one another. They are an opening between nerve cells that allow electrical activity to pass from one neuron to another.

When an individual has a terrifying experience, there is often a lingering fear of the place where it happened. This occurs because the nerve cells in certain brain regions increase their ability to excite or stimulate one another, said Fanselow, leader of the study and member of UCLA’s Brain Research Institute.

So far, most studies have emphasized that this experience happens because of the communication among neurotransmitters moving across synapses (spaces between neurons). However, there is also direct electrical contact among other small, inhibitory neurons in these areas as well, and these connect through gap junctions, Fanselow said.

“I was completely surprised by this discovery,” he added. “I really thought we were taking a long shot and was surprised that gap junctions were not only playing a role but that their importance was so great.”

Interestingly, these gap junctions are very common in invertebrates but rare in mammals, where they can only be found on certain inhibitory interneurons.

“Because of this, no one has looked at the importance of these gap junctions for learning, memory and emotion,” Fanselow said. “We hypothesized that these gap junctions may be very important. Because the gap junctions cause the inhibitory neurons to fire together, they may cause these inhibitory neurons to act as a pacemaker for the excitatory neurons, making them fire at the same time so they are better able to make fear memories.”

The study included the use of several drugs that block gap junctions in rats, and it was discovered that because the medications disrupted vital rhythms in the dorsal hippocampus (a brain region most associated with cognition), they were able to keep any “fear of place” memories from forming.

The drug injections worked when given right after a frightening experience, revealing that they could be particularly useful for PTSD.  Also, the drugs were just as effective when regularly injected into a cavity near the abdomen as when put directly into the brain.

“Because we don’t know when a person will experience trauma, treatments that can work after the experience hold more promise,” Fanselow said.

“Our research shows a way that neurons can coordinate their activity, and this coordination is critical for memory formation,” Fanselow said. “Perhaps if we had a way of enhancing gap junction function, we may improve memory formation by facilitating gap junctions when memory is impaired by diseases such as Alzheimer’s. However, we have not shown this yet.”

Fanselow noted that the formation of fear memories is what drives anxiety disorders, which are quite common and can be very debilitating. “Gap junctions appear to be key in coordinating the activity of the network of neurons that produce fear memories, specifically, and probably other memories, generally, as well,” he said.

Source:  University of California

Source Site: http://psychcentral.com/news/2011/01/10/research-may-yield-new-drug-targets-for-memory-anxiety-disorders/22437.html

The Year of Living Anxiously

by Henry Emmons, M.D.

The Anxiety Resolutions


There are sure-fire ways to make yourself anxious, if you wanted to do so. No one would do this on purpose, yet without knowing it that is exactly what many of us do every day. How do we do it? Here’s my list of some of the most common mistakes that aggravate the condition we call anxiety. But first I’d like to comment on stress.

In my opinion, stress has gotten a bad rap. Life is stressful, and always has been. Yet when we feel like ourselves, we are naturally resilient. We adapt to stresses remarkably well, often finding ourselves stronger or more skilled by having confronted life’s unavoidable challenges.

Stress alone is not the problem. Instead, we become our own enemy. The common mistakes that follow will reliably turn everyday stress into overwhelming anxiety:

1.) Keep thinking about what is wrong.
Neuroscience has confirmed what we already know: when we replay worrying thoughts again and again, we strengthen the neural pathways for those thoughts, so that they become ingrained in our mind like bad habits. It is as if we are rehearsing worry and anxiety. As with anything, we get better and better at it with practice.

2.) Keep talking about what is wrong.
Pop psychology has given us the notion that it is good to express our feelings. That can be true, but many of us take that to mean that we should “vent”. If someone is willing to listen, we often share our stories of woe. Repeated unloading keeps our anxious feelings alive and may even strengthen them.


3.) Over-stimulate yourself.
Caffeine, tobacco, loud noise, driving fast, working without breaks, skipping meals-there are so many ways to keep the body and brain on overdrive and keep the anxiety levels high.

4.) Don’t allow for time to refresh and renew.
After a stressful experience, it is normal and healthy to take time to rest and recover. That lets the body’s stress response system calm down, reset and get prepared for the next challenge. Our ancestors ran and then they rested; we stay on the treadmill. Not allowing for downtime differentiates our response to stress from every other time in human history.

5.) Stay constantly busy.
This is a variation on the last point. It is not only during the stressful times in life that we overdo. Most of us do too much every single day. You may have heard the phrase: “We are human beings, not human doings.” We are simply not designed to be on the go 24/7.

6.) Give in to your cravings.
Most of us reach reflexively, without thinking, without deciding, for something to soothe ourselves when we feel stressed or anxious. We often eat comfort food like sweets or other food laden with carbs and fats. Whatever we crave, we crave it because it makes us feel better-for much too short a time. Unfortunately, the comfort is brief and we almost always end up feeling worse in the long run.

7.) Short-change your sleep.


If there were a single sure-fire way to break a person down, it would have to be too little sleep. Lack of sleep is an accelerator toward most mental illness, and anxiety is no exception. Getting an average of 7-8 hours per night is not only helpful, it is essential.

8.) Stay sedentary.
Think about what happens in nature: the “fight or flight” reaction means that stress hormones flood the body, priming it for some kind of physical action. Sitting most of the day means the stress hormones have nothing to do but re-circulate. Moving your body helps to discharge the effects of all of those stress hormones and reset yourself back to a normal resting state.

9.) Isolate yourself.
It is a wonder that so many have become isolated and alone when we are clearly wired to connect. As the Dalai Lama has said, “We can live without religion and meditation, but we cannot survive without human affection.” Meaningful connection doesn’t solve everything, but it goes a very long way toward helping us endure the difficult side of life.

10.) Believe that you’re in it on your own.
The spiritual traditions give us a consistently reassuring message: “All will be well.” But when our brains get locked into anxious patterns, we can’t believe that. We see our small, individual selves as being solely responsible for our lives without any support. It is an illusion. If we can see through it, we can tap into a deep well of reassurance and hope.

11.) Watch the news daily.
You’ve heard that we are what we eat. We may also be what we take in through our eyes and ears. A study in Scandinavia showed that watching the evening news, filled with stories of tragedy, violence or other bad news, had a strong effect on rates of anxiety and depression. Does that mean that we should keep our head in the sand? No, but it may be wise to pay attention to what we are feeding ourselves through our minds, especially when we are going through personally hard times.

12.) Play video games.
It should come as no surprise that a game that simulates trauma and violence would put the brain into a state that is similar to the real thing. Researchers have found that common video games do just that. They may even create lasting brain changes so that things don’t go right back to normal when the game is done. The news is not all bad for video games, though. Soldiers in Iraq who played an absorbing game like Tetrus shortly after witnessing a trauma were able to protect themselves from developing post-traumatic stress symptoms.

13.) Become addicted to stress.
Some people appear to thrive on stress. They choose to remain overly committed, or constantly create high drama in their lives, and they seem to do fine. But if the stress stops, things begin to crumble. It is as if they have become addicted to stress and the high level of stress hormones that flood their body. Take the stress away, and they go into a form of withdrawal. Since no one can remain stressed forever without consequences, they should heed the warning signs and get a handle on their stress level.

We would do well to avoid what we can of the above pitfalls, but we won’t do it perfectly any more than we can keep all of our resolutions to do the right things. If we are in the game of life, stress cannot be avoided. That is all the more reason to become better at dealing with it.

Depression Thwarts Attempts to Quit Smoking

By RICK NAUERT PHD Senior News Editor
Reviewed by John M. Grohol, Psy.D. on January 3, 2011


New research suggests diagnosed or undiagnosed depression can hinder an individual’s efforts to stop smoking.

In the study, published in the January 2011 edition of the American Journal of Preventive Medicine. scientists determined approximately 24 percent of surveyed callers to the California Smokers’ Helpline currently suffered from major depression and 17 percent of callers had mild depression.

Over half the surveyed callers, depressed or not, made at least one attempt to quit after calling the helpline.

At the two-month mark, however, the success rate of those with major depression was much lower than that of mildly depressed or non-depressed callers. Nearly one in five callers with major depression reported success, but of others, nearly one in three was able to remain smoke-free.

Most quit-lines do not assess smokers for depression, even though mild depression already is known to reduce the success of quitting. This study suggests that major depression reduces the success rate even farther.

That is important because the California quit-line receives a high number of calls from heavy smokers and smokers on Medicaid – two circumstances associated with depression. Since more than 400,000 smokers call U.S. quit-lines every year, the authors believe that up to 100,000 depressed smokers nationally are not getting the targeted treatment they need.

“Assessing for depression can predict if a smoker will quit successfully, but the assessment would be more valuable if it were linked to services,” said lead study author Kiandra Hebert, Ph.D., of the University of California at San Diego.

Hebert said an integrated health care model is a potential solution. Depressed smokers could have better quitting success if they receive services that address both issues. Quit-lines, which are extremely popular, are in a good position to offer such services to a large number of depressed smokers and to pass on the services they develop to quit-lines across the country.

Treatment programs, including quit-lines, report that a growing number of callers have other disorders, such as depression, said Wendy Bjornson, co-director of the Oregon Health & Science University Smoking Cessation Center, who was not involved in the study.

“The results of this study are important. They show the scope of the problem and point to the need for protocols that can lead to better outcomes.”

Source: Health Behavior News Service

Risk for Alcoholism Linked to Risk for Obesity

ScienceDaily


The researchers noted that the association between a family history of alcoholism and obesity risk has become more pronounced in recent years. Both men and women with such a family history were more likely to be obese in 2002 than members of that same high-risk group had been in 1992.

“In addiction research, we often look at what we call cross-heritability, which addresses the question of whether the predisposition to one condition also might contribute to other conditions,” says first author Richard A. Grucza, PhD. “For example, alcoholism and drug abuse are cross-heritable. This new study demonstrates a cross-heritability between alcoholism and obesity, but it also says — and this is very important — that some of the risks must be a function of the environment. The environment is what changed between the 1990s and the 2000s. It wasn’t people’s genes.”

Obesity in the United States has doubled in recent decades from 15 percent of the population in the late 1970s to 33 percent in 2004. Obese people — those with a body mass index (BMI) of 30 or more — have an elevated risk for high blood pressure, diabetes, heart disease, stroke and certain cancers.

Reporting in the Archives of General Psychiatry, Grucza and his team say individuals with a family history of alcoholism, particularly women, have an elevated obesity risk. In addition, that risk seems to be growing. He speculates that may result from changes in the food we eat and the availability of more foods that interact with the same brain areas as addictive drugs.

“Much of what we eat nowadays contains more calories than the food we ate in the 1970s and 1980s, but it also contains the sorts of calories — particularly a combination of sugar, salt and fat — that appeal to what are commonly called the reward centers in the brain,” says Grucza, an assistant professor of psychiatry. “Alcohol and drugs affect those same parts of the brain, and our thinking was that because the same brain structures are being stimulated, overconsumption of those foods might be greater in people with a predisposition to addiction.”

Grucza hypothesized that as Americans consumed more high-calorie, hyper-palatable foods, those with a genetic risk for addiction would face an elevated risk from because of the effects of those foods on the reward centers in the brain. His team analyzed data from two large alcoholism surveys from the last two decades.

The National Longitudinal Alcohol Epidemiologic Survey was conducted in 1991 and 1992. The National Epidemiologic Survey on Alcohol and Related Conditions was conducted in 2001 and 2002. Almost 80,000 people took part in the two surveys.

“We looked particularly at family history of alcoholism as a marker of risk,” Grucza explains. “And we found that in 2001 and 2002, women with that history were 49 percent more likely to be obese than those without a family history of alcoholism. We also noticed a relationship in men, but it was not as striking in men as in women.”

Grucza says a possible explanation for obesity in those with a family history of alcoholism is that some individuals may substitute one addiction for another. After seeing a close relative deal with alcohol problems, a person may shy away from drinking, but high-calorie, hyper-palatable foods also can stimulate the reward centers in their brains and give them effects similar to what they might experience from alcohol.

“Ironically, people with alcoholism tend not to be obese,” Grucza says. “They tend to be malnourished, or at least under-nourished because many replace their food intake with alcohol. One might think that the excess calories associated with alcohol consumption could, in theory, contribute to obesity, but that’s not what we saw in these individuals.”

Grucza says other variables, from smoking, to alcohol intake, to demographic factors like age and education levels don’t seem to explain the association between alcoholism risk and obesity.

“It really does appear to be a change in the environment,” he says. “I would speculate, although I can’t really prove this, that a change in the food environment brought this association about. There is a whole slew of literature out there suggesting these hyper-palatable foods appeal to people with addictive tendencies, and I would guess that’s what we’re seeing in our study.”

The results, he says, suggest there should be more cross-talk between alcohol and addiction researchers and those who study obesity. He says there may be some people for whom treating one of those disorders also might aid the other.

This work was supported by grants from the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse of the National Institutes of Health.

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Washington University School of Medicine.

A National Institute of Depression?

by Jonathan Rottenberg, Ph.D


I am reading Siddharta Murkherjee’s, wonderful, Emperor of All Maladies: A Biography of Cancer. One of the stories it tells is about the formation of the National Cancer Insitute in 1937. Here is the current mission statement of the NCI:

* Supports and coordinates research projects conducted by universities, hospitals, research foundations, and businesses throughout this country and abroad through research grants and cooperative agreements.
* Conducts research in its own laboratories and clinics.
* Supports education and training in fundamental sciences and clinical disciplines for participation in basic and clinical research programs and treatment programs relating to cancer through career awards, training grants, and fellowships.
* Supports research projects in cancer control.
* Supports a national network of cancer centers.
* Collaborates with voluntary organizations and other national and foreign institutions engaged in cancer research and training activities.
* Encourages and coordinates cancer research by industrial concerns where such concerns evidence a particular capability for programmatic research.
* Collects and disseminates information on cancer.
* Supports construction of laboratories, clinics, and related facilities necessary for cancer research through the award of construction grants.
which over time became a major institute within the National Institutes of Health.

In other words, the NCI is a national coordinating body for research and training to reduce the menace of cancer.

If we look across the National Insitutes of Health we see that many conditions have an institute. Alcohol has an institute. Drug Abuse does. Diabetes is covered. Stroke. Allergies. Check, check.

But not depression.

Depression is soon to become the emperor of all maladies. Serious depression affects nearly a fifth of the population and it is booming, especially in the young. If you need a call to action, look at the graph below from the National Comorbidity Study Replication, a comprehensive national survey of mental health in the United States. It shows that young people aged 18 to 29 have already experienced as much depression as people aged 60+, even though they have lived for less than half as long on planet earth.

Although it is hard to quantify the suffering caused by depression, it is straightforward to make sound estimates of its overall burden — for example the financial costs of lost work time and increased use of health care dollars. When you do the math, depression already ranks up there with the most burdensome disorders. The World Health Organization projects that in less than 10 years, depression will be the 2nd most burdensome condition. That’s greater, by the way, than cancer.

A National Institute on Depression makes sense not only because there is an urgent public health need but because there is so much about depression that we still don’t know. In my last post, I pointed out one striking example:  A recent search revealed only one well-designed  prospective study of the depressive prodrome (i.e., warning symptoms that herald depression). And much of our knowledge about depression isn’t well coordinated. We don’t do a good job of even knowing what we already know.

Poor integration of existing knowledge is one of the major limitations of the current national approach to depression. Thus, in addition to giving a new NID the broad mission along the lines of the NCI, it would be important for the NID to allow room for many approaches, not only the exclusive focus on genes and brains that has yielded relatively modest results so far but cognitive, sociological, and anthropological perspectives as well.

In our times of fiscal retrenchment, it’s easy to shoot down any new initiatives. But at the same time, wouldn’t keeping our current approach to depression be far riskier to the public health? and more costly in the long run? The time is right to make a modest investment to expand federal research on depression and bring together the work that’s currently done in several NIH insitutes (Mental Health, Aging, Child Health and Development) into a stand-alone National Insitute of Depression. If not now, when?