Extreme stress, fear linked to mental illnessby Heather WoolwinePublic Relations This article is the last in a series of four concerning the 2004 Update in Psychiatry. On June 5, Dennis Charney, M.D., chief of the Mood and Anxiety Disorder Research Program for the National Institute of Mental Health, presented several models for resilience and vulnerability in terms of acute stress and neuromechanisms associated with reward, fear conditioning and extinction, and social behavior. While much research and documentation of what happens when people don’t deal well with stress exists, Charney highlighted some traits that seem to facilitate resilience in the face of stress. He mentioned optimism, good intellectual functioning, effective self-regulation of emotions and attachment behaviors, a positive self-concept, altruism, an active coping style, the ability to disclose emotions, and social support as tools to combat all types of stress. But for those who do not have most of these traits, responses to stress may evolve into anxiety disorders, and there are psychological characteristics that researchers say directly relate to those disorders. Anxiety sensitivity (AS) is an individual’s response to physiological changes associated with anxiety or fear. Patients with anxiety disorders demonstrate exaggerated physiological reactions to stress because they misinterpret bodily cues and misperceive sensations as harmful or dangerous. Associated with a selective cognitive bias towards threat, it predicts the frequency and intensity of panic attacks and appears to be a trait abnormality that increases the risk for anxiety disorders. Behavioral inhibition (BI), an inherited predisposition to increased physiological reactivity and anxious symptoms in unfamiliar environments, makes some individuals more vulnerable to anxiety disorders. About 20 percent of children have BI, but the environment-gene interaction is key to its manifestation. These children seem to be more susceptible to anxiety disorders or post-traumatic stress disorder (PTSD) after stressful events. Charney said, “Although the phenotype and genotype associated with AS and BI have yet to be defined, a recent study revealed the presence of amygdala hyperactivity in adult subjects with BI in their child history.” He further elaborated the clinical importance in learning more about the interaction between environment and genetic risk factors and their role in increasing the risk of anxiety disorders. Charney used a study of U.S. Army Special Forces (SERE) and U.S. Navy Special Forces (SEAL) training to demonstrate vulnerability and resilience models and their relationship with severe stress situations. He mentioned several neural mechanisms related to resilience and vulnerability to extreme stress, including reward, Pavlovian fear conditioning, inhibitory avoidance, reconsolidation, extinction, and social behavior. He suggested that Pavlovian fear conditioning may account for common clinical observations in panic disorder, PTSD, and depression, and that sensory and cognitive stimuli associated with or resembling the original trauma elicit panic attacks, flashbacks, and autonomic symptoms. Excessive stress mediates the release of certain hormones and neurochemicals in the brain that facilitate the development of fear memories and thus, contextual fear, or inhibitory avoidance, may lead to chronic anxiety or depressive symptoms. Repeated activation and reconsolidation may further strengthen the memory trace and lead to persistence of trauma-related symptoms, and failure in neural mechanisms of extinction may relate to persistent traumatic memories, re-experiencing symptoms, autonomic hyperarousal, and phobic behaviors. A stress-induced reduction in dopamine and increases in certain transcription produce a dysfunction in reward circuitry leading to anhedonia and hopelessness. Offering a “resilience prescription,” Charney detailed the following for the attendees:
Gorman delivered the last presentation of the conference, offering numerous studies and preclinical data demonstrating that the lateral nucleus of the amygdala is critically involved in the conditioned fear memory. He said that conditioned fear in animals is a reasonable model of fear and anxiety in humans, and patients with anxiety disorders have a lower threshold for activation of the amygdala than non-anxious subjects. “At the same time, we and others have shown that other parts of a neural circuitry that we have called fear circuitry are also important in fear memory,” Gorman said. “For example, areas within the prefrontal cortex, including the anterior cingulate and the orbitofrontal cortex, modulate amygdala activity and abnormalities in these pathways also appear important in the pathophysiology of anxiety disorders. Knowledge of the neuroanatomy and molecular biology of fear enables us to evaluate the mechanism of action of effective anti-anxiety therapies and to predict new treatment interventions that may be superior to those currently in use.” According to Gorman, anxiety disorders and/or depression represent abnormalities
of an evolutionarily conserved fear mechanism. Brain circuits that subserve
fear responses in experimental animals are involved in human fear and anxiety
disorders, like the amygdala, hippocampus, and the prefrontal cortex. Current
treatments for anxiety disorder interact with multiple brain systems including
the fear system. He suggested that strategies for improved anxiolytic and
antidepressant therapies are directed toward more specific interaction
with the fear system.
Friday, July 9, 2004
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