Self-rated health : biobehavioral determinants with focus on inflammatory factors

• Self-rated (subjective) health is an independent predictor of future mortality, but neither the mechanisms behind this relation nor the biological determinants of poor self-rated health are known. Inflammatory cytokines give rise to a sickness response which includes fatigue, malaise, anhedonia and pain, resembling factors that are known to impact negatively on self-rated health. It is therefore possible that cytokines that cause a sickness response are important mediators in subjective health perception. This thesis investigated biobehavioral determinants of self-rated health, with a primary focus on inflammatory cytokines. The study populations included women patients from a primary health care center (Study I), women from a population based study on memory and aging in Umeå (Study II), men and women from a population based prospective study in Stockholm (Study III), and men in a laboratory study on the effects of experimentally restricted sleep (Study IV). A main finding was that higher (or increased) levels of inflammation related cytokines were associated with poor (or deteriorated) self-rated health; interleukin (IL)-1β, IL-1ra and tumor necrosis factor (TNF)-α in study I, and IL-6 in study II and IV. The observed association between higher levels of cytokines and poor self-rated health was shown to be stronger with increased age. Of psychological factors, positive affect turned out to be a more important determinant of self-rated health as compared to negative affect. In study III, the relation between leptin, a cytokine-like marker for available energy in the body, and self-rated health was investigated. Higher levels of leptin were associated to poor self-rated health in men, while instead predicting better future self-rated health in women. Moreover, self-rated health was associated to further sick-leave in both men and women. In study IV, subjective health - framed to represent the prevailing day - deteriorated gradually when sleep was restricted to 4 h per night, and returned to baseline levels after two days of recovery. This decrease in subjective health was significantly correlated with increased levels of circulating IL-6. This thesis presents increased support for an immune component of subjectively perceived health. It also implies that more short-term perspectives, e.g. in relation to changes in health behaviors such as sleep, should be taken into account when understanding subjective health perception. The results are of importance for understanding the psychobiological underpinnings of self-rated health and may give clues to explain its well-established association to future health.

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