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 Research & Giving News Article  Anxiety disorders are among one of the most common psychiatric illnesses affecting both children and adults (approximately 19 million American adults). Several disorders fall into this category, including: Panic Disorder, Obsessive-Compulsive Disorder, Post-Traumatic Stress Disorder, Phobias (including Social Phobia also known as Social Anxiety Disorder), and Generalized Anxiety Disorder. These disorders can result in extensive anxiety and fear for an individual, are chronic and may become worse if not treated. Anxiety can be exhibited by mood disturbances, and/or disturbances of thinking, behavior and physiological activity. Currently, treatments may include medication and/or psychosocial therapies or some combination of these. Medications used to treat anxiety disorders may include Selective Serotonin Reuptake Inhibitors (SSRIs), tricyclic antidepressants, benzodiazepines, azipirones, beta blockers, and monoamine oxidase inhibitors (MAOIs). Psychosocial therapies may include psychotherapy, cognitive-behavioral therapies or behavioral therapies. NARSAD researchers are exploring every facet of anxiety disorders in an attempt to unravel their complex nature and develop appropriate interventions. Research is aimed at discovering the origins and improved treatments, and may lead to important breakthroughs for early identification and improved outcomes. Anxiety--What Happens in the Brain Robert Sapolsky, Ph.D., (NARSAD 2004 Distinguished Investigator) of Stanford University, notes that the neurobiological aspects of anxiety are now becoming clearer, with attention focused on the effects of stress and trauma upon the amygdala, its role in mediating conditioned fear, and how repeated major stressors can increase amygdaloid activation of the autonomic nervous system. Specifically, this involves stress enhancing synaptic strength in the amygdala and causing amygdala neurons to form new dendritic branches. The stress effects seem to be mediated by glucocorticoids, the adrenal steroid hormones secreted during stress. Dr. Sapolsky is constructing stress-inducible vectors that will be introduced into the amygdala to express genes that will block amygdala hyperexcitation during a stressful event, or to block downstream steps that mediate the stress-induced increase in amygdala activation. He hopes to better understand fear and anxiety, as well as improve gene therapy for trauma and anxiety. Jack Nitschke, Ph.D., (NARSAD 2005 Young Investigator) of University of Wisconsin, Madison, notes that anticipating aversion, danger, and other unpleasant circumstances helps prepare for and prevent negative outcomes. However, anticipatory overprocessing can be excessive in disorders such as anxiety and results in significant suffering. Dr. Nitschke has already identified several areas involved in anticipating negative events, including the amygdala, insula, prefrontal cortex, and anterior cingulate, which serve functions such as detecting threat and evaluating negative stimuli. He is investigating the neural correlates of the abnormalities in anticipation of negative events in people with social phobia, with results pointing the way to improved treatments for anxiety, while placing greater emphasis on problems with anticipation and the brain substrates involved. Christopher Wright, M.D., Ph.D., (NARSAD 2004 Young Investigator) of Harvard University, is investigating yet another piece of the amygdala’s involvement in anxiety. He is using functional magnetic resonance imaging (fMRI) to look at the effects of D-cycloserine (DCS), a partial activator of the excitatory glutamate receptor and a possibly useful pharmacological agent in the treatment of anxiety and other disorders, on the amygdala in normal subjects. He believes that administering DCS to the subjects while they are viewing fearful faces will result in a heightened decline of amygdala activity. He believes this will provide new insights into the effect of DCS on the human amygdala, as well as assessing specific drug effects on brain structures implicated in anxiety and other disorders. Animal Models—What They Teach Us about Anxiety Mice are used as one of the favored models in research, as they are biologically and genetically similar to humans and their genetic material can be easily manipulated. Important information about specific disorders, such as anxiety, can be gained by utilizing mouse models. Stephan Anagnostaras, Ph.D., (NARSAD 2003 Young Investigator) of Emory University, is using a mouse model to study genetic vulnerability in humans with anxiety disorders to understand the relationship among various behavioral measures of unlearned anxiety and conditioned fear at a mathematical level to develop indices for these two constructs that are more robust than current approaches. Masato Asai, M.D., (NARSAD 2005 Young Investigator) of Children’s Hospital, Boston, is using a mouse model to investigate the effects of corticotrophin-releasing hormone (CRH/CRF) in the brain which has been linked to anxiety-related behaviors in animals and humans. In mice genetically altered to have high CRH levels in tissues that normally make CRH, he will determine if CRH is elevated in areas of the brain thought to be associated with anxiety and if this causes the mice to have increased anxiety-like behaviors in non-stressed and stressed conditions. If his hypothesis proves correct, this may help explain different levels of anxiety in humans. Hagit Cohen, Ph.D., (NARSAD 2003 Young Investigator) of Ben Gurion University, is using a rat model to investigate Post Traumatic Stress Disorder (PTSD), a chronic condition that occurs after life-threatening or horrific traumatic events. By investigating the behavior of animals that have already been exposed to a traumatic event, he hopes to distinguish and analyze the response of those that respond in an exaggerated manner to a similar event. He believes this mimics the posttraumatic stress response in humans, and will provide important information, including marked abnormalities in the endocrine system. Obsessive Compulsive Disorder—Identification, Genetics and Treatment Obsessive Compulsive Disorder (OCD), classified as an anxiety disorder, usually begins in childhood or adolescence and affects up to 3 percent of people in their lifetime. It is characterized by anxious thoughts and/or rituals that a person feels powerless to control. Many people can identify with some of the symptoms of OCD, such as checking and re-checking to make certain that a door has been locked. However, the actual disorder is more pervasive, and often involves disturbing, repetitive thoughts, and/or rituals the individual may perform over and over again (though these provide only temporary relief of the anxious feelings). The following OCD studies provide an overview for the areas of research being conducted on all of the anxiety disorders. Scientists are exploring early identification techniques, genetic implications and new, advanced treatment options. Edward Thomas Bullmore, Ph.D., (NARSAD 2004 Distinguished Investigator) of Addenbrookes Hospital, is using neuroimaging techniques on subjects with OCD to examine the cortico-striato-thalamic brain systems, and to develop brain imaging as a method of identifying endophenotypic markers (indicators of a specific disorder which must be measured, but cannot be seen by the naked eye) for improved identification purposes. Early identification and subsequent efficacious treatment are often associated with improved outcomes in many psychiatric disorders. OCD is believed to be genetic, and is associated with an abnormal brain circuit. Paul Arnold, M.D., (NARSAD 2004 Young Investigator) of University of Toronto, has found genetic associations between certain genetic variants and OCD and is now using neuroimaging techniques to determine if brain circuit abnormalities that cause OCD are the result of inherited variations in genes affecting the action of the neurotransmitter glutamate. Increased knowledge of these circuits may lead to improved treatment strategies and early identification of OCD. Vladimir Coric, M.D., (NARSAD 2003 Young Investigator) of Yale University, based on the information that current medications, such as serotonin-reuptake inhibitors (SRI’s) or dopamine antagonists only provide some, but not full, symptom relief, believes that other neurochemical systems must be involved in OCD. Specific receptors called cannabinoid receptors are thought to directly alter glutamatergic function in individuals with OCD. He plans to use the pharmacological agent dronabinol to evaluate its efficacy in people with OCD who have not experienced amelioration of their symptoms with SRI’s, providing valuable information for possible new treatment. Conclusion Anxiety disorders have been the focus of intense investigation, with the hope that research will yield answers and provide steps for creating improved identification strategies, better treatments and eventual cures. NARSAD researchers are conducting work in all areas of anxiety disorders, and the above-mentioned studies provide just a sampling of the many current outstanding research projects in anxiety. Results from these studies, and others like them, are critical in bringing much-needed relief to those who experience the often disabling symptoms of anxiety. |
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