In their review “The Role of Stress in Neurodegenerative Diseases and Mental Disorders,” Tobias Esch and colleagues assess the impact of stress as a cause or an enhancer of neurological and neuroendocrine disorders including Alzheimer’s, Depression, and Post-traumatic stress disorder.

1. Fatima Traore<br />Nicole Weekes<br />Independent Study<br />April 19th, 2010<br />Stress, Neurodegenerative Diseases, and Mental Illnesses<br />Part of the literature suggests a role of stress in the pathophysiology of many neurodegenerative diseases and mental illnesses. Although there is still little evidence for stress as a triggering factor, it has been established that a small acute stress can be beneficial in the diseases processes while chronic excessive stress can be detrimental. Hippocampal neurodegeneration and plasticity seem to be instrumental in the progressive pathology of neurological illnesses. In their review “The Role of Stress in Neurodegenerative Diseases and Mental Disorders,” Tobias Esch and colleagues assess the impact of stress as a cause or an enhancer of neurological and neuroendocrine disorders including Alzheimer’s, Depression, and Post-traumatic stress disorder.<br />Two systems, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) mediate the cascade of events that occur to produce the stress response. They work together to maintain a dynamic balance of endocrine activity in the body. Environmental and internal (psychological) stressors can disregulate this balance, thereby increasing the work of the HPA and the SNS systems. Both hypoactivation and hyperactivation of these systems can damage an organism’s health and physiology. For instance, Post-traumatic stress disorder is associated with a hyperactivity of the HPA axis, and a permanent state of anxiety that increase the risks of cardiovascular diseases and immunodeficiency. Similar symptoms are observed after chronic stress. The pathophysiological effects of stress are also connected to hippocampal activity—a structure important in learning and memory---where neurodegeneration has also been observed. <br />Neurodegenerative Diseases<br />There is strong evidence that stress impairs learning and memory functions both in experimental and healthy control groups. In Alzheimer’s disease, high levels of stress and arousal disturb hippocampal activation and the HPA/SNS mediated processes, suppressing hippocampal activity and inducing hippocampal atrophy. Moreover, steroids seem to be the main effectors in the neurodegeneration of cells in the hippocampus. It has been proposed that they may change hippocampal plasticity, and reduce the number as well as alter the structure of dendritic spines--structures associated with learning and memory-- but their mechanism of action is unknown as yet. Meanwhile, the aging hippocampus is increasingly susceptible to stress. Excessive stress activity and strenuous exercise can also trigger an inflammatory response that is dangerous for the immune and vascular systems. Alzheimer’s disease with a neuropathology characterized by the appearance of neurofibrillary tangles and amyloid plaques is influenced by oxidative stress and chronic inflammation. The profound memory loss and dementia of Alzheimer’s patients is definitely caused by a neurodegeneration in the hippocampus. The factors above mentioned, altogether, might explain the loss of memory and cognitive functions of patients suffering of Alzheimer’s disease.<br />Neuropsychological Diseases<br />As of anxiety and depression, chronic activation of the SNS has been linked to their onset. Part of the literature has showed that prenatal and early postnatal exposure to chronic stress contributes to individual differences in the stress response reactivity, which increases susceptibility to depression later on in life. In many instances, this type of stress seems to be triggered by a childhood trauma. On a molecular level, nitric oxide may play a role in the physiopathology of depression and anxiety because of its involvement in the underlying mechanisms of the stress-related responses. An overactivity of the norepinephrenic system due to chronic SNS hyperactivity is a factor in the development of Depression and Anxiety. Besides, an excessive activation of the HPA axis, which results in hypercortisolism, is also of importance. In sum, both the HPA and SNS systems affect perhaps the onset, development, and progression of depression and anxiety. <br />In Post-traumatic stress disorder, an individual develops a chronic condition that is characterized by re-experience of the event, avoidance and hyper-arousal after exposure to a traumatic stressor. Although PTSD is mainly considered as a psychological disorder, a neurobiological basis to the disorder has been demonstrated. More specifically, PTSD patients experience an overactivation of the HPA axis as well as abnormal levels of cortisol. <br />With regard to schizophrenia, there is evidence from behavioral and biological data that stress worsens the symptoms of Schizophrenia. Similarly to other neuropsychiatric disorders, hypercortisolism has also been observed in schizophrenic patients as a result of an abnormal activity of the HPA axis. <br />The underlying mechanism could be an increase in the synthesis of dopamine or a change in dopaminergic receptors’ functions due to the hyperactivity of the HPA axis. Meanwhile, alterations in dopaminergic receptors and in the hippocampus increase the patient’s sensibility to stress. There is also evidence that insufficient interaction between cortical and subcortical dopamine neurons is part of the problem. This disruption is possibly due to stress. Although stress effects are not all consistent with the pathology observed in schizophrenia---no gliosis, minimal neurodegeneration of hippocampal cells, and rare abnormal cortisol levels—it could be an significant environmental factor in the onset and pathogenesis of the disorder. <br />To conclude, stress may play a major role in the pathophysiology of many diseases. Stressful stimuli can be either environmental or intrinsic (such as a psychological disturbance). In our modern society, stressors are ubiquitous; we encounter them in relationships, work, or traumatic events. Despite the fact that stress has not been shown to cause certain diseases, an arguably strong correlation has been found between mental disorders and stress effects. These effects could be important in the onset, development and/or progression of the disorders. In several cases -- Alzheimer’s disease and Schizophrenia for instance—it seems to induce neurodegeneration in the hippocampus, and to disturb normal activity of the HPA/SNS axes. It may also enhance sensitivity and susceptibility to the diseases. However, further research is much needed to elucidate the specific underlying mechanisms of the stress action. Meanwhile, patients and healthy individuals could use coping and stress-management strategies for prevention as suggested by the authors of the article. <br />References<br />Esch, T., Stefano, G. B., Fricchione, G. L., & Benson, H. (2002). The role of stress in neurodegenerative diseases and mental disorders. Neuroendocrinology Letters, 23(3), 199-208.<br />