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Anxiety Disorders
Research
at the
National Institute of Mental Health
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 other
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
functioning 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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