Mental disorders as risk factors, comorbidities, and consequences of cancer

Cancer and mental disorders are both heterogenous groups of diseases and with substantial public health burden. Accumulating evidence has supported an elevated risk of mental disorders among patients with cancer. Different explanations might underlie the association of cancer with the subsequent risk of mental disorders, including cancer-related inflammation, cancer treatment, and psychological distress in relation to receiving a diagnosis of and being treated for a life-threatening disease. The association of mental disorders with the subsequent risk of cancer is on the other hand largely unclear, though several hypotheses have been proposed to support such an association, including chronic inflammation, dysregulation of neurotransmitters (e.g., monoamine), and altered activity of hypothalamic–pituitary–adrenal axis and neuroplasticity. This thesis work aimed therefore to understand the role of mental disorders on cancer, as risk factors, comorbidities, and consequences. In Paper I, we assessed whether there was an association between clinical diagnosis of autism spectrum disorder (ASD) and risk of cancer. Based on the Swedish national population and health registers, we conducted a nationwide population-based cohort study during 1987-2016 and found an elevated risk of cancer at early life among individuals with ASD, compared with individuals without ASD. The risk elevation was predominantly ascribable to ASD with co-occurring intellectual disability (ID) and/or birth defects, whereas ASD without these comorbidities was not related to an elevated risk of cancer. In Paper II, we examined the association between clinical diagnosis of ID and risk of cancer, based on a nationwide population-based cohort study during 1973-2016 using Swedish national population and health registers. We found an elevated risk of overall cancer and eleven subtypes of cancer in individuals with ID (age ≤43 years), compared with individuals free of ID. The risk elevation was more pronounced for syndromic ID and not likely attributable to familial confounding. In Paper III, we estimated risk of psychiatric disorders and cardiovascular diseases among individuals undergoing a diagnostic work-up of potential hematological malignancy during 2005-2014, based on the Skåne Healthcare Register. We observed highly increased risks of psychiatric disorders and cardiovascular diseases among individuals undergoing a diagnostic work-up of suspected hematological malignancy, irrespective of the ultimate diagnosis. In Paper IV, we evaluated the relationship between precancer psychiatric disorders and risk of subsequent sepsis among individuals with cancer during 2006-2014, based on the Swedish Cancer Register. We found an association between precancer psychiatric disorders and elevated risk of sepsis among individuals with cancer, calling for expanded surveillance and prevention of sepsis among cancer patients with precancer psychiatric disorders. In conclusion, Papers I and II showed that ID, as well as ASD when comorbid with ID and/or birth defect, were risk factors of cancer. Paper III showed that individuals undergoing diagnostic work-up of suspected hematological malignancy were at highly increased risks of psychiatric disorders and cardiovascular diseases, irrespective of the ultimate diagnosis. Paper IV showed that precancer psychiatric disorders were related to an elevated risk of sepsis subsequent to cancer diagnosis

The Time Course Effects of Electroacupuncture on Promoting Skeletal Muscle Regeneration and Inhibiting Excessive Fibrosis after Contusion in Rabbits

The aim of this study was to investigate the longitudinal effects of electroacupuncture (EA) on Zusanli (ST36) and Ashi acupoints in promoting skeletal muscle regeneration and inhibiting excessive fibrosis after contusion in rabbits. Sixty rabbits were randomly divided into four groups: normal, contusion, EA, and recombinant human insulin-like growth factor-I (rhIGF-I). An acute skeletal muscle contusion was produced on the right gastrocnemius (GM) by an instrument-based drop-mass technique. EA was performed for 15 minutes every two days with 0.4 mA (2 Hz), and GM injections were executed with rhIGF-I (0.25 mL once a week). Rabbits treated with EA had a higher T-SOD and T-AOC serum activities and lower MDA serum level, the blood perfusion of which was also significantly higher. In the EA group, the diameter of the myofibril was uniform and the arrangement was regular, contrary to the contusion group. The number and diameter of regenerative myofibers and MHC expression were increased in the EA group. EA treatment significantly decreased fibrosis formation and reduced both GDF-8 and p-Smad2/3 expressions in injured muscle. Our data indicate that EA may promote myofiber regeneration and reduce excessive fibrosis by improving blood flow and antioxidant capacities. Additionally, EA may regulate signaling factor expression after contusion

Risk of head and neck cancer in relation to blood inflammatory biomarkers in the Swedish AMORIS cohort

BackgroundInflammation is critically involved in the development of human cancer, and blood inflammatory biomarkers have been proposed to indicate the risk of different cancer types.MethodsUsing the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) Cohort (N=812,073), we first performed a time-to-event analysis to evaluate the association of the baseline level of 12 blood inflammatory biomarkers measured during 1985-1996 with the subsequent risk of head and neck cancer (HNC) identified through the nationwide Swedish Cancer Register until end of 2020. A nested case-control study was further conducted to demonstrate the longitudinal trends of the studied biomarkers during the 30-year period prior to diagnosis of HNC.ResultsIn the time-to-event analysis, we identified a total of 2,510 newly diagnosed HNC cases. There was an increased risk of HNC per standard deviation (SD) increase of haptoglobin (hazard ratio [HR]: 1.25; 95% confidence interval [CI]: 1.21-1.30), leukocytes (HR: 1.22; 95%CI: 1.17-1.28), sedimentation rate (HR: 1.17; 95%CI: 1.07-1.29), and monocytes (HR: 1.34; 95%CI: 1.07-1.68) at baseline, after adjustment for age, sex, fasting status, occupational status, and country of birth. In contrast, there was a decreased risk of HNC per SD increase of lymphocytes in % (HR: 0.85; 95%CI: 0.73-0.99) and lymphocyte-to-monocyte ratio (LMR) (HR: 0.81; 95%CI: 0.69-0.95) at baseline. In the nested case-control study using repeatedly measured biomarker levels, we found that individuals with HNC had consistently higher levels of haptoglobin, leukocytes, sedimentation rate, and monocytes, as well as consistently lower levels of lymphocytes in % and LMR, during the 30-year period prior to diagnosis, compared to controls.ConclusionBased on a cohort of more than half a million participants with up to 35 years of follow-up, our findings provide solid evidence supporting the presence of alterations in blood inflammatory biomarkers during the decades before diagnosis of HNC