Search

Background and Hypothesis Gut microbiota alterations have been reported in severe mental illness (SMI) but fewer studies have probed for signs of gut barrier disruption and inflammation. We hypothesized that gut leakage of microbial products due to intestinal inflammation could contribute to systemic inflammasome activation in SMI. Study Design We measured plasma levels of the chemokine CCL25 and soluble mucosal vascular addressin cell adhesion molecule-1 (sMAdCAM-1) as markers of T cell homing, adhesion and inflammation in the gut, lipopolysaccharide binding protein (LBP) and intestinal fatty acid binding protein (I-FABP) as markers of bacterial translocation and gut barrier dysfunction, in a large SMI cohort (n = 567) including schizophrenia (SCZ, n = 389) and affective disorder (AFF, n = 178), relative to healthy controls (HC, n = 418). We assessed associations with plasma IL-18 and IL-18BPa and leukocyte mRNA expression of NLRP3 and NLRC4 as markers of inflammasome activation. Study Results Our main findings were: (1) higher levels of sMAdCAM-1 (P =.002), I-FABP (P = 7.6E−11), CCL25 (P = 9.6E−05) and LBP (P = 2.6E−04) in SMI compared to HC in age, sex, BMI, CRP and freezer storage time adjusted analysis; (2) the highest levels of sMAdCAM-1 and CCL25 (both P = 2.6E−04) were observed in SCZ and I-FABP (P = 2.5E−10) and LBP (3) in AFF; and (3), I-FABP correlated with IL-18BPa levels and LBP correlated with NLRC4. Conclusions Our findings support that intestinal barrier inflammation and dysfunction in SMI could contribute to systemic inflammation through inflammasome activation. [ABSTRACT FROM AUTHOR]

In some settings, it may be difficult to differentiate between a confounder and a mediator. For instance, the observed association of self-reported childhood psychological abuse (CPA) with onset of chronic obstructive pulmonary disease (COPD) and migraine may be confounded by current mood/psychological state (e.g., the subjective evaluation of one's own affective state), as well as mediated by an individual's psychopathological symptoms. In this study, we propose the "independence hypothesis," which could prove meaningful to explore in data that lack prospective or objective indices of CPA. We used cross-sectional data from wave VI (2007-2008) of the Tromsø Study, Norway (N = 12,981). The associations between CPA and COPD and migraine were assessed with Poisson regression models. CPA was associated with a 46% increased risk of COPD (relative risk [RR] = 1.46, 95% confidence interval [CI]: [1.02, 1.90]) and a 28% increased risk of migraine in adulthood (RR = 1.28, 95% CI: [1.04, 1.53]), independent of age, sex, parental history of psychiatric problems/asthma/dementia, smoking, respondent's mood/psychological state, and mental health. These findings suggest that the association between retrospectively reported CPA and COPD and migraine is not driven entirely by respondent's mood/psychological state and mental health. Assessing the independent effect of self-reported CPA on COPD and migraine in retrospective studies may prove more meaningful than exploring the mediating role of mental health. Here, we provide the analytical rationale for assessing the independent effect in settings where it is difficult to differentiate between a confounder and a mediator. Moreover, we provide a theoretical rationale for assessing the independent effect of retrospectively reported childhood adversity on health and well-being. [ABSTRACT FROM AUTHOR]

A personal narrative is presented which explores the author's experience as a Pakistani graduate student in Norway.