Issues in the design and implementation of psychoneuroimmunology research.

Research that uses a psychoneuroimmunology (PNI) framework seeks to determine whether valid associations exist among stress, immune function, and health. These associations are difficult to conclusively determine due to the fact that PNI research is fraught with methodological difficulties. These difficulties arise from the multifaceted and complex nature of the neuro-endocrine-immune network that is the phenomenon of interest in PNI. This article discusses multiple issues of which investigators should be aware when designing and implementing PNI research including (1) the control of potentially immunomodulating variables related to demographics, behavior, and lifestyle; (2) the manner in which stress, endocrine function, immunity, and health outcomes are measured in consideration of the theoretical relevance to the research question, population, or disease entity understudy; (3) the way physiological specimens are procured and stored; and (4) the methods by which assays are performed.