Anxiety Disorders Research at the National Institute of Mental Health

Anxiety disorders research going on at the National Institute of Mental Health (NIMH).

More than 19 million adult Americans ages 18 to 54 have anxiety disorders. The National Institute of Mental Health (NIMH) supports research into the causes, diagnosis, prevention, and treatment of anxiety disorders and mental illnesses. This research is conducted both in the Institute's intramural laboratories and in biomedical research institutions across the country. Studies examine the genetic and environmental risks for major anxiety disorders, their course, both alone and when they co-occur with other illnesses such as heart disease or depression, and their treatment. Scientists seek to discover the basis of anxiety disorders in the brain and their effects on the fu and other nctioning of the brain and other organs. The ultimate goal is to be able to cure, and perhaps even to prevent, anxiety disorders.

Types of Anxiety Disorders

The term anxiety disorders encompasses several clinical conditions:

• panic disorder, in which feelings of extreme fear and dread strike unexpectedly and repeatedly for no apparent reason, accompanied by intense physical symptoms
• obsessive-compulsive disorder (OCD), characterized by intrusive, unwanted, repetitive thoughts and rituals performed out of a feeling of urgent need
• post-traumatic stress disorder (PTSD), a reaction to a terrifying event that keeps returning in the form of frightening, intrusive memories and brings on hypervigilance and deadening of normal emotions
• phobias, including specific phobia a fear of an object or situation and social phobia a fear of extreme embarrassment
• generalized anxiety disorder (GAD), exaggerated worry and tension over everyday events and decisions

Research Progress

NIMH research has led to advances in understanding the causes of these disorders and how to treat them. Today, the majority of people with panic disorder and OCD improve significantly within weeks or months of getting proper treatment. The same is true for people with phobias. And many people with PTSD and generalized anxiety disorder also make substantial improvement with treatment.

As the search continues for better treatments, NIMH is harnessing the most sophisticated scientific tools available to determine the causes of anxiety disorders. Like heart disease and diabetes, these brain disorders are complex and probably result from the interplay of genetic, behavioral,developmental, and other factors. Scientists in a number of disciplines are trying to identify risk factors that make certain people prone to these conditions.

Studies of the Brain and Anxiety Disorders

Studies in animals and humans have focused on pinpointing the specific brain areas and circuits involved in anxiety and fear, which underlie anxiety disorders. Fear, an emotion that evolved to deal with danger, causes an automatic, rapid protective response that occurs without the need for conscious thought. It has been found that the body's fear response is coordinated by a small structure deep inside the brain, called the amygdala.

Neuroscientists have shown that when confronted with danger, the body's senses launch two sets of signals to different parts of the brain. One set of signals, which takes a more roundabout route, relays information to the cerebral cortex, the cognitive part of the brain that explains in detail the threatening object or situation such as a big black car heading for you as you cross the street. The other set of signals shoots straight to the amygdala, which sets the fear response in motion, readying the body for quick action before the cognitive part of the brain comprehends just what is wrong. The heart starts to pound and diverts blood from the digestive system to the muscles for quick action. Stress hormones and glucose flood the blood stream to provide the energy to fight or flee. The immune system and the pain response are suppressed to prevent swelling and discomfort, which could interfere with a quick escape. And, as a preventive measure for similar confrontations in the future, the learned fear response is etched on the amygdala.

How Does this Learned Fear Response Turn into an Anxiety Disorder?

One or more fearful experiences can prime a person to respond excessively to situations where most people would experience no fear such as in the supermarket or only moderate nervousnesss such as giving a speech. In anxiety disorders, the deeply etched memory can result in hypervigilance, making it hard to focus on other things, and leading to feelings of anxiety in many situations. In people who have survived overwhelming trauma and developed PTSD, for example, even mild reminders of the trauma may initiate the fear response. People with specific or social phobia often completely avoid their feared situation. In panic disorder the chronic worry about having another attack may lead to stress-related conditions such as heart problems and irritable bowel syndrome. In people with generalized anxiety disorder, the chronic anxiety may prevent them from focusing on even the simplest tasks. The amygdala, although relatively small, is a very complicated structure, and recent research with animals suggests that different anxiety disorders may be associated with activation in different parts of the amygdala.

Brain Findings Point the Way to New Approaches

The amygdala findings may have important implications for treating people who suffer from anxiety disorders. If, as studies suggest, the memories stored in the amygdala are relatively indelible, one aim of research is to develop therapies for anxiety disorders that increase cognitive control over the amygdala so that the "act now, think later" response can be interrupted.

Clinical Trials of New Treatments

Anxiety disorder treatment studies have been designed so that pharmacological and cognitive or behavioral therapies can be tested head-to-head. In one clinical trial, two separate centers are examining how well drug and behavioral therapies work separately and together in the treatment of OCD. Data collected from this study should help scientists determine if one of the treatments works better than the other in decreasing obsessions and compulsions.

In addition, the direct comparison of the combined treatment with the medication will provide much needed information on whether the high relapse rate associated with stopping the drug can be reduced. The comparison should also help determine if the medication can enhance compliance with the behavioral treatment.

Many of the current medications for anxiety disorders affect the neurotransmitter serotonin. New treatment approaches are examining drugs that affect other neurotransmitters and brain chemicals such as GABA, gamma-aminobutyric acid, and Substance P. A new research tool, magnetic resonance spectroscopy will help scientists measure brain levels of GABA and other substances.

Researchers are also looking at combinations of medications that may have a synergistic effect in panic disorder, for example, studies are underway to determine if an antidepressant medication that affects serotonin works better when used with the new antianxiety drug buspirone.

The Role of Cognitive Factors

Cognitive factors play a significant role in the onset of anxiety disorders. People at risk for these disorders tend to be overly responsive to potentially threatening stimuli. Studies are underway to look at how people with anxiety disorders process information. The goal is to see which cognitive capabilities are affected by anxiety and which are free to handle other information. Data collected from the studies should help researchers determine more about the brain pathology associated with anxiety disorders.

Early Life Stress May Play a Role

In animals, NIMH-funded researchers are studying how stress, especially when it occurs in early life, affects how adverse events are handled later in life. Rat pups who are subjected to the stress of being separated from their mothers for several minutes early in life have, months later, a much greater startle reaction to a stressful event than pups who were never separated. This line of research may help scientists learn how genes and experience affect who is vulnerable and who is resistant to anxiety disorders.

Anxiety Disorders and Hormones

Another area of research has led to the discovery that anxiety disorders are associated with abnormal levels of certain hormones. People with PTSD, for example, tend to be low on the stress hormone cortisol, but have an overabundance of epinephrine and norepinephrine, which could be why they continue to feel anxious after the trauma. In addition, they tend to have higher-than-usual levels of corticotropin releasing factor (CRF), which switches on the stress response and may explain why people with PTSD startle so easily. Scientists are researching ways to correct hormonal imbalances and bring symptoms under control.

The Importance of Imaging Tools

Scientists may be closer than ever before to creating therapies that are specifically targeted. NIMH studies use imaging tools to allow researchers to peer into the living brain and watch the amygdala, the cortex, and other areas of the brain at work. They can identify abnormal activity when a person has an anxiety disorder and determine if medication or cognitive and behavioral therapies help to correct it.

Recent studies of the brain using magnetic resonance imaging showed that people with OCD had significantly less white matter than did control subjects, suggesting a widely distributed brain abnormality in OCD.

Imaging studies are also looking at how brain structure may be related to PTSD. A part of the brain involved in emotion, called the hippocampus, tends to be smaller in some people with PTSD. NIMH-funded researchers are trying to decipher whether that is a result of extreme stress responses related to the trauma or whether people who already have a smaller hippocampus are more prone to PTSD.

NIMH Anxiety Research and Genetics

Research evidence points to genetics as a factor in the origin of anxiety disorders. Scientists have recently discovered a gene that influences fearfulness in mice. And NIMH-supported studies of twins have found that genes play a role in panic disorder and social phobia. Although genes help determine whether someone will develop an anxiety disorder, heredity alone can't explain what goes awry. Experience also plays a part. In PTSD, for example, the trauma is the experience that triggers the anxiety disorder; genetic factors may help explain why only certain individuals exposed to similartraumatic events develop full-blown PTSD. Researchers are honing in on the degree of influence that genetics and experience exert in each of the anxiety disorders information they hope will yield clues to prevention and treatment.

Some Cases of OCD Linked to Earlier Infection

NIMH studies of obsessive-compulsive disorder in young people have shown that the experience of having a streptococcal bacterial infection may lead to the development of crippling obsessions and compulsions. It appears that a genetic vulnerability, coupled with rheumatic fever, is associated with some cases of OCD. Preliminary evidence indicates that special treatment for the infection improves or cures the OCD.

The Broad NIMH Research Program

In addition to studying anxiety disorders, NIMH supports and conducts a broad based, multidisciplinary program of scientific inquiry aimed at improving the diagnosis, prevention, and treatment of other mental disorders. These conditions include bipolar disorder, clinical depression, and schizophrenia.

Increasingly, the public as well as health care professionals are recognizing these disorders as real and treatable medical illnesses of the brain. Still, more research is needed to examine in greater depth the relationships among genetic, behavioral, developmental, social and other factors to find the causes of these illnesses. NIMH is meeting this need through a series of research initiatives:

• NIMH Human Genetics Initiative
  This project has compiled the world's largest registry of families affected by schizophrenia, bipolar disorder, and Alzheimer's disease. Scientists are able to examine the genetic material of these family members with the aim of pinpointing genes involved in the diseases.
• Human Brain Project
  This multi-agency effort is using state-of-the-art computer science technologies to organize the immense amount of data being generated through neuroscience and related disciplines, and to make this information readily accessible for simultaneous study by interested researchers.
• Prevention Research Initiative
  Prevention efforts seek to understand the development and expression of mental illness throughout life so that appropriate interventions can be found and applied at multiple points during the course of illness. Recent advances in biomedical, behavioral, and cognitive sciences have led NIMH to formulate a new plan that marries these sciences to prevention efforts.

While the definition of prevention will broaden, the aims of research will become more precise and targeted.

Source: NIMH, Dec. 2000

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