"Environmental Etiologies of Neurological Disorders: Modifiers of Risk: Genes, Age, Gender, Nutrition, Simultaneous Exposures, Socio-Economic Status". It has become increasingly evident that many human neurological diseases and disorders arise from complex interactions of multiple risk factors, of which environmental chemical exposures may serve as one contributing risk. Other environmental and host factors, such as genetic background, stage of development, dietary status, immune status, obesity, stress, socioeconomic status, gender, aging, behavior, and intercurrent disease state, as well as simultaneous chemical exposures, can also contribute. For example, Parkinson's disease exhibits gender differences, and protection is conferred by caffeine and smoking. The impact of neurotoxicants like lead and methylmercury is heavily influenced by developmental windows, with children showing significantly greater vulnerability. Thus, a full understanding of the true risk posed by any environmental toxicant for human neurological diseases or disorders will ultimately require assessments of its interaction with other relevant environmental, host and genetic risk factors and other modifiers of effect.

Despite these complexities, the paradigms used to understand the impact of environmental exposures as risk factors for human diseases continue to rely on approaches that fail to capture this reality. Instead, they focus on exposures to single chemicals in isolation from other risk factors. Animal studies often examine effects of a single chemical in young adult, mostly male rodents, ignoring, for instance, the potential importance of age and gender. Epidemiological and clinical studies generally focus on main effects of environmental exposures, since risk modification, as reflected in statistical interactions, is considered inaccessible because of inadequate sample sizes. Consequently, as models of diseases and disorders, current research approaches are distant from actual human conditions, constraining the ability to determine pathophysiological mechanisms from which biomarkers and therapeutic strategies can be identified, thereby limiting the ability to protect human health.

An understanding of the interactions of host and environmental risk factors with environmental chemical exposures in the etiology of neurological diseases and disorders allows the development of increasingly more realistic and valid animal models of disease, and more focused clinical /epidemiological studies. Refined animal and human models will expedite the discovery of pathophysiological mechanisms of environmentally-related diseases and disorders, and thus improve the ability to define biomarkers of disease onset and progression, as well as potential targets for therapeutic interventions, thereby leading to improved prevention and detection strategies. Understanding how risk factors interact is also critical in the context of global public health protection, since different populations and cultures bring different sets of risk factors into play.

U13ES016515

2007-09-15

2008-08-31