man social activities as making business decisions involve neuroendocrine mechanisms conserved across mammals, if not other species (Morse, 2006).

DEFINITIONS FROM ANIMAL RESEARCH

Animal research has clarified concepts that are key to understanding the effects of social environment on health and disease and gene function, extending and moderating the conclusions based on epidemiological studies in humans. These concepts include genetics, immune and neuroendocrine function, causality, pleitropy, and life-span fitness.

Genetics

Genetics requires a broad conception that includes both functional genomics (intra-individual changes in gene expression over time) and the more traditional topic of structural polymorphism (interindividual variations in DNA sequence or epigenetic characteristics). This broad conceptualization is essential because social influences on gene transcription are fairly well studied, while few studies have examined the relationships between social factors and genetic polymorphisms. That such effects exist is likely because structural polymorphisms generally exert their effects in the context of expressed genes.

Physiology: The Missing Link

An essential role of animal research is to test the relationship between presumptive genetic influences (e.g., inferred from studies of heritability) and defined genetic influences (e.g., effects attributable to the expression of specific genes or epigenetic characteristics). The immune system includes classical immune cells (e.g., leukocytes) as well as other cellular contexts relevant to disease pathogenesis or host defense, such as somatic cells responding to pathogens through innate immune responses (e.g., “danger signals” produced by Toll-like receptors, Type I interferon production). The neuroendocrine system also is broadly defined to include not only true neurally driven hormone production (e.g., hypothalamic-pituitary-adrenal [HPA] axis), but also neuroeffector processes that do not necessarily involve systemic hormone distribution (e.g., local effects of neurotransmitter release from autonomic or sensory neurons or neuropeptides such as vasopressin and oxytocin).

Part of the reason so few genetic determinants of immune response currently are presently known may be an overly restrictive focus on “immune system” genes. Polymorphisms in many “nonimmune” genes, which are regulated by the psychosocial environment through physiological systems, may also influence leukocyte function and/or the pathogenesis of



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