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.

List of scientific papers

I. Liu Q, Yin W, Meijsen JJ, Reichenberg A, Gådin JR, Schork AJ, Adami HO, Kolevzon A, Sandin S, Fang F. Cancer risk in individuals with autism spectrum disorder. Ann Oncol. 2022;33:713-719.
https://doi.org/10.1016/j.annonc.2022.04.006

II. Liu Q, Adami HO, Reichenberg A, Kolevzon A, Fang F, Sandin S. Cancer risk in individuals with intellectual disability in Sweden: A population-based cohort study. PLoS Med. 2021;18:e1003840.
https://doi.org/10.1371/journal.pmed.1003840

III. Liu Q, Andersson TM, Jöud A, Shen Q, Schelin ME, Magnusson PK, Smedby KE, Fang F. Cardiovascular diseases and psychiatric disorders during the diagnostic workup of suspected hematological malignancy. Clin Epidemiol. 2019;11:1025-1034.
https://doi.org/10.2147/CLEP.S218063

IV. Liu Q, Song H, Andersson TM, Magnusson PKE, Zhu J, Smedby KE, Fang F. Psychiatric disorders are associated with increased risk of sepsis following a cancer diagnosis. Cancer Res. 2020;80:3436-3442.
https://doi.org/10.1158/0008-5472.CAN-20-0502