Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment

Veterans of Operation Desert Storm/Desert Shield - the 1991 Gulf War (GW) - are a unique population who returned from theater with multiple health complaints and disorders. Studies in the U.S. and elsewhere have consistently concluded that approximately 25-32% of this population suffers from a disorder characterized by symptoms that vary somewhat among individuals and include fatigue, headaches, cognitive dysfunction, musculoskeletal pain, and respiratory, gastrointestinal and dermatologic complaints. Gulf War illness (GWI) is the term used to describe this disorder. In addition, brain cancer occurs at increased rates in subgroups of GW veterans, as do neuropsychological and brain imaging abnormalities. Chemical exposures have become the focus of etiologic GWI research because nervous system symptoms are prominent and many neurotoxicants were present in theater, including organophosphates (OPs), carbamates, and other pesticides; sarin/cyclosarin nerve agents, and pyridostigmine bromide (PB) medications used as prophylaxis against chemical warfare attacks. Psychiatric etiologies have been ruled out. This paper reviews the recent literature on the health of 1991 GW veterans, focusing particularly on the central nervous system and on effects of toxicant exposures. In addition, it emphasizes research published since 2008, following on an exhaustive review that was published in that year that summarizes the prior literature (RACGWI, 2008). We conclude that exposure to pesticides and/or to PB are causally associated with GWI and the neurological dysfunction in GW veterans. Exposure to sarin and cyclosarin and to oil well fire emissions are also associated with neurologically based health effects, though their contribution to development of the disorder known as GWI is less clear. Gene-environment interactions are likely to have contributed to development of GWI in deployed veterans. The health consequences of chemical exposures in the GW and other conflicts have been called "toxic wounds" by veterans. This type of injury requires further study and concentrated treatment research efforts that may also benefit other occupational groups with similar exposure-related illnesses

Optimization of stress response through the nuclear receptor-mediated cortisol signalling network

It is an accepted paradigm that extended stress predisposes an individual to pathophysiology. However, the biological adaptations to minimize this risk are poorly understood. Using a computational model based upon realistic kinetic parameters we are able to reproduce the interaction of the stress hormone cortisol with its two nuclear receptors, the high-affinity glucocorticoid receptor and the low-affinity pregnane X-receptor. We demonstrate that regulatory signals between these two nuclear receptors are necessary to optimize the body’s response to stress episodes, attenuating both the magnitude and duration of the biological response. In addition, we predict that the activation of pregnane X-receptor by multiple, low-affinity endobiotic ligands is necessary for the significant pregnane X-receptor-mediated transcriptional response observed following stress episodes. This integration allows responses mediated through both the high and low-affinity nuclear receptors, which we predict is an important strategy to minimize the risk of disease from chronic stress

Higher Cortisol Levels Following Exposure to Traumatic Reminders in Abuse-Related PTSD

FSW - Self-regulation models for health behavior and Psychopathology - Ou

Integrating NIMH Research Domain Criteria (RDoC) into PTSD Research

Three and a half decades of research on posttraumatic stress disorder (PTSD) has produced substantial knowledge on the pathobiology of this frequent and debilitating disease. However, despite all research efforts, so far no drug that has specifically targeted PTSD core symptoms progressed to clinical use. Instead, although not overly efficient, serotonin re-uptake inhibitors continue to be considered the gold standard of PTSD pharmacotherapy. The psychotherapeutic treatment and symptom-oriented drug therapy options available for PTSD treatment today show some efficacy, although not in all PTSD patients, in particular not in a substantial percent of those suffering from the detrimental sequelae of repeated childhood trauma or in veterans with combat related PTSD. PTSD has this in common with other psychiatric disorders - in particular effective treatment for incapacitating conditions such as resistant major depression, chronic schizophrenia, and frequently relapsing obsessive-compulsive disorder as well as dementia has not yet been developed through modern neuropsychiatric research.In response to this conundrum, the National Institute of Mental Health launched the Research Domain Criteria (RDoC) framework which aims to leave diagnosis-oriented psychiatric research behind and to move on to the use of research domains overarching the traditional diagnosis systems. To the best of our knowledge, the paper at hand is the first that has systematically assessed the utility of the RDoC system for PTSD research. Here, we review core findings in neurobiological PTSD research and match them to the RDoC research domains and units of analysis. Our synthesis reveals that several core findings in PTSD such as amygdala overactivity have been linked to all RDoC domains without further specification of their distinct role in the pathophysiological pathways associated with these domains. This circumstance indicates that the elucidation of the cellular and molecular processes ultimately decisive for regulation of psychic processes and for the expression of psychopathological symptoms is still grossly incomplete. All in all, we find the RDoC research domains to be useful but not sufficient for PTSD research. Hence, we suggest adding two novel domains, namely stress and emotional regulation and maintenance of consciousness. As both of these domains play a role in various if not in all psychiatric diseases, we judge them to be useful not only for PTSD research but also for psychiatric research in general