Khandker, Maheruh2018-11-282018-11-282018-09https://hdl.handle.net/11299/201167University of Minnesota Ph.D. dissertation.September 2018. Major: Epidemiology. Advisors: Bernard Harlow, Logan Spector. 1 computer file (PDF); viii, 93 pages.Background: There has been increasing attention on chronic stressors and their influence on various chronic disorders. Prospective and observational and studies have shown associations between early-life chronic stressors (e.g., childhood abuse) and various chronic illnesses. However, little is known about the psychobiological mechanisms linking the two. One plausible contributing mechanism is perseverative cognition. Defined as the repetitive cognitive representation of a psychological stressor, perseverative cognition can extend the psychological and physiological effects of stress contributing to chronic disease etiology. Using retrospective and prospective studies, this dissertation will examine the role of rumination, a manifestation of perseverative cognition, in the development of two very distinct chronic disorders in women: 1) vulvodynia, a chronic pain disorder and 2) prediabetes, a precursor to the metabolic disorder Type 2 diabetes mellitus. Methods: Three different manuscripts were written to explore early-life stressors, the role of rumination as a stress response, and the onset of chronic disorders vulvodynia and prediabetes. The first manuscript aimed to examine the role of rumination on the onset of vulvodynia. A psychosocial survey with questions specific to early-life traumatic events and rumination were administered to 185 matched case-control pairs of women with and without vulvodynia. Conditional logistic regression was used to examine associations between rumination constructs (i.e., total, emotion-focused, instrumental, and searching for meaning) and vulvodynia onset. Conditional logistic regression was also used to determine whether these associations depended upon early-life stressors (i.e., severity of childhood abuse and of self-reported antecedent traumatic events). Age at interview, antecedent pain disorders, any childhood abuse, and antecedent psychiatric morbidity were included as covariates. The second manuscript, in the same matched pairs, delved further into the role of rumination on the onset of two key vulvodynia phenotypes: 1) primary and secondary onset and, 2) localized and generalized areas of pain. Conditional logistic regression was used to examine associations between rumination constructs and onset of each of the vulvodynia phenotypes. Conditional logistic regression was also used to determine whether these associations depended upon the presence of early-life stressors. Age at interview, antecedent pain disorders, any abuse, and antecedent psychiatric morbidity were included as covariates. The third manuscript examined the associations between rumination and incident prediabetes in a prospective study. The participants were 1,326 white and black women aged 25-37 years without prediabetes or diabetes at baseline (examination year 7; 1992-1993) in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Incident prediabetes was estimated based on measures obtained at examination years 10, 15, 20 and 25. Trait rumination was assessed by the Spielberger Trait Anxiety Inventory. Tertiles of trait rumination (i.e., total rumination, bother rumination, keen rumination, and tense rumination) were used to evaluate the hazard of incident prediabetes using Cox regression. All analyses were conducted on SAS 9.4, with a 2-sided type 1 error of 0.05 considered statistically significant. Results: In the first manuscript: Vulvodynia was associated with the highest tertile of emotion-focused (OR=2.1; 95% CI: 1.2, 3.2) and instrumental (OR=2.1; 95% CI: 1.1, 4.0) rumination. These associations were attenuated following additional adjustment for antecedent psychiatric morbidity. Among women who reported rumination about early-life stressors prior to vulvar pain in cases or matched reference age in controls, those with vulvodynia were over 2-times more likely to report the highest tertile of total rumination (OR=2.3; 95% CI:1.1, 5.0) compared to those without vulvodynia. In the second manuscript: Primary and localized vulvodynia were both associated with instrumental rumination (OR=5.2; 95% CI: 1.9, 14.6 and OR=3.0; 95%CI:1.2, 8.0, respectively). These associations were attenuated following additional adjustment for depression; associations with localized vulvodynia became non-significant. No associations were observed for secondary vulvodynia or for generalized vulvodynia. When examining rumination stratified by early-life stressors, localized and generalized vulvodynia were both associated with rumination among women who reported higher levels of trauma severity (OR=7.9; 95% CI 1.8, 34.1) and OR=5.2; 95% CI (1.2, 22.9), respectively). In the third manuscript: After adjusting for covariates, there was a 35% higher incidence of prediabetes in women who were in the highest tertile of bother rumination compared to those in the lowest tertile of bother rumination (HR=1.35; 95% CI: 1.05, 1.75) after adjustment for potential confounders. This association was attenuated following additional adjustment for depression. No other trait rumination constructs were associated with incidence of prediabetes. Among women with a history of childhood physical abuse, there was a 2.2-fold higher incidence of prediabetes in women who were in the highest tertile of bother rumination compared to women who reported being in the lowest tertile of bother rumination (HR=2.23; 95% CI: 1.37, 3.64); there were no associations among women who did not have a history of childhood physical abuse. Conclusion: Outcomes of this dissertation will help to understand the psychobiological mechanisms of vulvodynia and prediabetes in women. Our findings indicate that a prolonged cognitive stress response (i.e., rumination) may be one important mechanism by which early-life stressors contribute to the onset of chronic disorders in women. The results may be useful in developing interventions for the prevention and treatment of these chronic disorders. Findings may also have implications for similar chronic pain syndromes and metabolic disorders in women.enchildhood abusechronic disorderschronic stressearly-life traumaruminationwomenThesis or Dissertation