Bidirectional association between autoimmune disease and perinatal depression: a nationwide study with sibling comparison.

Although major depression, characterized by a pro-inflammatory profile, genetically overlap with autoimmune disease (AD) and the perinatal period involve immune system adaptations and AD symptom alterations, the bidirectional link between perinatal depression (PND) and AD is largely unexplored. Hence, the objective of this study was to investigate the bidirectional association between PND and AD. Using nationwide Swedish population and health registers, we conducted a nested case-control study and a matched cohort study. From 1,347,901 pregnancies during 2001-2013, we included 55,299 incident PND, their unaffected full sisters, and 10 unaffected matched women per PND case. We identified 41 subtypes of AD diagnoses recorded in the registers and compared PND with unaffected population-matched women and full sisters, using multivariable regressions. Women with an AD had a 30% higher risk of subsequent PND (95% CI 1.2-1.5) and women exposed to PND had a 30% higher risk of a subsequent AD (95% CI 1.3-1.4). Comparable associations were found when comparing exposed women with their unaffected sisters (nested case-control OR: 1.3, 95% CI 1.2-1.5, matched cohort HR: 1.3, 95% CI 1.1-1.6), and when studying antepartum and postpartum depression. The bidirectional association was more pronounced among women without psychiatric comorbidities (nested case-control OR: 1.5, 95% CI 1.4-1.6, matched cohort HR: 1.4, 95% CI 1.4-1.5) and strongest for multiple sclerosis (nested case-control OR: 2.0, 95% CI 1.6-2.3, matched cohort HR: 1.8, 95% CI 1.0-3.1). These findings demonstrate a bidirectional association between AD and PND independent of psychiatric comorbidities, suggesting possibly shared biological mechanisms. If future translational science confirms the underlying mechanisms, healthcare providers need to be aware of the increased risk of PND among women with ADs and vice versa.

Association of pre-existing depression and anxiety with Omicron variant infection.

Pre-existing psychiatric disorders were linked to an increased susceptibility to COVID-19 during the initial outbreak of the pandemic, while evidence during Omicron prevalence is lacking. Leveraging data from two prospective cohorts in China, we identified incident Omicron infections between January 2023 and April 2023. Participants with a self-reported history or self-rated symptoms of depression or anxiety before the Omicron pandemic were considered the exposed group, whereas the others were considered unexposed. We employed multivariate logistic regression models to examine the association of pre-existing depression or anxiety with the risk of any or severe Omicron infection indexed by medical interventions or severe symptoms. Further, we stratified the analyses by polygenic risk scores (PRSs) for COVID-19 and repeated the analyses using the UK Biobank data. We included 10,802 individuals from the Chinese cohorts (mean age = 51.1 years, 45.6% male), among whom 7841 (72.6%) were identified as cases of Omicron infection. No association was found between any pre-existing depression or anxiety and the overall risk of Omicron infection (odds ratio [OR] =1.04, 95% confidence interval [CI] 0.95-1.14). However, positive associations were noted for severe Omicron infection, either as infections requiring medical interventions (1.26, 1.02-1.54) or with severe symptoms (≥3: 1.73, 1.51-1.97). We obtained comparable estimates when stratified by COVID-19 PRS level. Additionally, using clustering method, we identified eight distinct symptom patterns and found associations between pre-existing depression or anxiety and the patterns characterized by multiple or complex severe symptoms including cough and taste and smell decline (ORs = 1.42-2.35). The results of the UK Biobank analyses corroborated findings of the Chinese cohorts. In conclusion, pre-existing depression and anxiety was not associated with the risk of Omicron infection overall but an elevated risk of severe Omicron infection, supporting the continued efforts on monitoring and possible early intervention in this high-risk population during Omicron prevalence.

Perinatal depression and risk of maternal cardiovascular disease: a Swedish nationwide study.

BACKGROUND AND AIMS: Increasing evidence suggests that some reproductive factors/hazards are associated with a future risk of cardiovascular disease (CVD) in women. While major (non-perinatal) depression has consistently been associated with CVD, the long-term risk of CVD after perinatal depression (PND) is largely unknown. METHODS: A nationwide population-based matched cohort study involving 55 539 women diagnosed with PND during 2001-14 in Sweden and 545 567 unaffected women individually matched on age and year of conception/delivery was conducted. All women were followed up to 2020. Perinatal depression and CVD were identified from Swedish national health registers. Using multivariable Cox models, hazard ratios (HR) of any and type-specific CVD according to PND were estimated. RESULTS: The mean age at the PND diagnosis was 30.8 [standard deviation (SD) 5.6] years. During the follow-up of up to 20 years (mean 10.4, SD 3.6), 3533 (6.4%) women with PND (expected number 2077) and 20 202 (3.7%) unaffected women developed CVD. Compared with matched unaffected women, women with PND had a 36% higher risk of developing CVD [adjusted HR = 1.36, 95% confidence interval (CI): 1.31-1.42], while compared with their sisters, women with PND had a 20% higher risk of CVD (adjusted HR = 1.20, 95% CI 1.07-1.34). The results were most pronounced in women without a history of psychiatric disorder (P for interaction < .001). The association was observed for all CVD subtypes, with the highest HR in the case of hypertensive disease (HR = 1.50, 95% CI: 1.41-1.60), ischaemic heart disease (HR = 1.37, 95% CI: 1.13-1.65), and heart failure (HR 1.36, 95% CI: 1.06-1.74). CONCLUSIONS: Women with PND are at higher risk of CVD in middle adulthood. Reproductive history, including PND, should be considered in CVD risk assessments of women.

The bidirectional association between premenstrual disorders and perinatal depression: A nationwide register-based study from Sweden.

BACKGROUND: Premenstrual disorders (PMDs) and perinatal depression (PND) share symptomology and the timing of symptoms of both conditions coincide with natural hormonal fluctuations, which may indicate a shared etiology. Yet, there is a notable absence of prospective data on the potential bidirectional association between these conditions, which is crucial for guiding clinical management. Using the Swedish nationwide registers with prospectively collected data, we aimed to investigate the bidirectional association between PMDs and PND. METHODS AND FINDINGS: With 1,803,309 singleton pregnancies of 1,041,419 women recorded in the Swedish Medical Birth Register during 2001 to 2018, we conducted a nested case-control study to examine the risk of PND following PMDs, which is equivalent to a cohort study, and transitioned that design into a matched cohort study with onward follow-up to simulate a prospective study design and examine the risk of PMDs after PND (within the same study population). Incident PND and PMDs were identified through clinical diagnoses or prescribed medications. We randomly selected 10 pregnant women without PND, individually matched to each PND case on maternal age and calendar year using incidence density sampling (N: 84,949: 849,482). We (1) calculated odds ratio (OR) and 95% confidence intervals (CIs) of PMDs using conditional logistic regression in the nested case-control study. Demographic factors (country of birth, educational level, region of residency, and cohabitation status) were adjusted for. We (2) calculated the hazard ratio (HR) and 95% CIs of PMDs subsequent to PND using stratified Cox regression in the matched cohort study. Smoking, BMI, parity, and history of psychiatric disorders were further controlled for, in addition to demographic factors. Pregnancies from full sisters of PND cases were identified for sibling comparison, which contrasts the risk within each set of full sisters discordant on PND. In the nested case-control study, we identified 2,488 PMDs (2.9%) before pregnancy among women with PND and 5,199 (0.6%) among controls. PMDs were associated with a higher risk of subsequent PND (OR 4.76, 95% CI [4.52,5.01]; p < 0.001). In the matched cohort with a mean follow-up of 7.40 years, we identified 4,227 newly diagnosed PMDs among women with PND (incidence rate (IR) 7.6/1,000 person-years) and 21,326 among controls (IR 3.8). Compared to their matched controls, women with PND were at higher risk of subsequent PMDs (HR 1.81, 95% CI [1.74,1.88]; p < 0.001). The bidirectional association was noted for both prenatal and postnatal depression and was stronger among women without history of psychiatric disorders (p for interaction < 0.001). Sibling comparison showed somewhat attenuated, yet statistically significant, bidirectional associations. The main limitation of this study was that our findings, based on clinical diagnoses recorded in registers, may not generalize well to women with mild PMDs or PND. CONCLUSIONS: In this study, we observed a bidirectional association between PMDs and PND. These findings suggest that a history of PMDs can inform PND susceptibility and vice versa and lend support to the shared etiology between both disorders.

Childhood maltreatment and risk of endocrine diseases: an exploration of mediating pathways using sequential mediation analysis.

BACKGROUND: Adverse childhood experiences (ACEs), including childhood maltreatment, have been linked with increased risk of diabetes and obesity during adulthood. A comprehensive assessment on the associations between childhood maltreatment and all major endocrine diseases, as well as the relative importance of different proposed mechanistic pathways on these associations, is currently lacking. METHODS: Based on the UK Biobank, we constructed a cohort including 151,659 participants with self-reported data on childhood maltreatment who were 30 years of age or older on/after January 1, 1985. All participants were followed from the index date (i.e., January 1, 1985, or their 30th birthday, whichever came later) until the first diagnosis of any or specific (12 individual diagnoses and 9 subtypes) endocrine diseases, death, or the end of follow-up (December 31, 2019), whichever occurred first. We used Cox models to examine the association of childhood maltreatment, treated as continuous (i.e., the cumulative number of experienced childhood maltreatment), ordinal (i.e., 0, 1 and ≥ 2), or binary (< 2 and ≥ 2) variable, with any and specific endocrine diseases, adjusted for multiple covariates. We further examined the risk of having multiple endocrine diseases using Linear or Logistic Regression models. Then, sequential mediation analyses were performed to assess the contribution of four possible mechanisms (i.e., suboptimal socioeconomic status (SES), psychological adversities, unfavorable lifestyle, and biological alterations) on the observed associations. RESULTS: During an average follow-up of 30.8 years, 20,885 participants received a diagnosis of endocrine diseases. We observed an association between the cumulative number of experienced childhood maltreatment and increased risk of being diagnosed with any endocrine disease (adjusted hazard ratio (HR) = 1.10, 95% confidence interval 1.09-1.12). The HR was 1.26 (1.22-1.30) when comparing individuals ≥ 2 with those with < 2 experienced childhood maltreatment. We further noted the most pronounced associations for type 2 diabetes (1.40 (1.33-1.48)) and hypothalamic-pituitary-adrenal (HPA)-axis-related endocrine diseases (1.38 (1.17-1.62)), and the association was stronger for having multiple endocrine diseases, compared to having one (odds ratio (95% CI) = 1.24 (1.19-1.30), 1.35 (1.27-1.44), and 1.52 (1.52-1.53) for 1, 2, and ≥ 3, respectively). Sequential mediation analyses showed that the association between childhood maltreatment and endocrine diseases was consistently and most distinctly mediated by psychological adversities (15.38 ~ 44.97%), while unfavorable lifestyle (10.86 ~ 25.32%) was additionally noted for type 2 diabetes whereas suboptimal SES (14.42 ~ 39.33%) for HPA-axis-related endocrine diseases. CONCLUSIONS: Our study demonstrates that adverse psychological sequel of childhood maltreatment constitutes the main pathway to multiple endocrine diseases, particularly type 2 diabetes and HPA-axis-related endocrine diseases. Therefore, increased access to evidence-based mental health services may also be pivotal in reducing the risk of endocrine diseases among childhood maltreatment-exposed individuals.

Adverse childhood experiences and psychological functioning among women with schizophrenia or bipolar disorder: population-based study.

BACKGROUND: Adverse childhood experiences (ACEs) are well-known risk factors for schizophrenia and bipolar disorder. AIMS: The aim was to study the associations between specific ACEs and psychological functioning in women with schizophrenia or bipolar disorder. METHOD: Among 29 367 women (mean age 44 years) from the Icelandic Stress-And-Gene-Analysis (SAGA) study, 534 (1.8%, mean age 40) reported having been diagnosed with schizophrenia or bipolar disorder, which were combined to 'severe mental disorders'. Participants reported on 13 types of ACEs, childhood deprivation and psychological functioning (defined as coping ability and current symptoms of depression, anxiety and sleep disturbances). Adjusted Poisson regression calculated prevalence ratios (PRs) between ACEs and severe mental disorders. Linear regression assessed the association between ACEs and psychological functioning among women with a severe mental disorder. RESULTS: Women with a severe mental disorder reported more ACEs (mean 4.57, s.d. = 2.82) than women without (mean 2.51, s.d. = 2.34) in a dose-dependent manner (fully-adjusted PR = 1.23 per ACE, 95% CI 1.20-1.27). After mutual adjustment for other ACEs, emotional abuse, sexual abuse, mental illness of a household member, emotional neglect, bullying and collective violence were associated with severe mental disorders. Among women with severe mental disorders, a higher number of ACEs was associated with increased symptom burden of depression (ß = 2.79, 95% CI = 1.19-4.38) and anxiety (ß = 2.04, 95% CI = 0.99-3.09) including poorer sleep quality (ß = 0.83, 95% CI = 0.07-1.59). Findings were similar for schizophrenia and bipolar disorder separately. CONCLUSION: Women with schizophrenia or bipolar disorder show a strong history of ACEs, which may interfere with their psychological functioning and, therefore, need to be addressed as part of their treatment, for example, with trauma-focused psychotherapy.

Associations of parental and perinatal factors with subsequent risk of stress-related disorders: a nationwide cohort study with sibling comparison.

Little is known about the contribution of pregnancy-related parental and perinatal factors to the development of stress-related disorders. We aimed to investigate whether parental/perinatal adversities entail higher risks of stress-related disorders in the offspring, later in life, by accounting for genetic and early environmental factors. Based on the nationwide Swedish registers, we conducted a population-based cohort study of 3,435,747 singleton births (of which 2,554,235 were full siblings), born 1973-2008 and survived through the age of 5 years. Using both population- and sibling designs, we employed Cox regression to assess the association between parental and perinatal factors with subsequent risk of stress-related disorders. We identified 55,511 individuals diagnosed with stress-related disorders in the population analysis and 37,433 in the sibling analysis. In the population-based analysis we observed increased risks of stress-related disorders among offspring of maternal/paternal age <25, single mothers, parity ≥4, mothers with BMI ≥ 25 or maternal smoking in early pregnancy, gestational diabetes, and offspring born moderately preterm (GA 32-36 weeks), or small-for-gestational-age. These associations were significantly attenuated toward null in the sibling analysis. Cesarean-section was weakly associated with offspring stress-related disorders in population [hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06-1.12] and sibling analyses (HR 1.10, 95% CI 1.02-1.20). Our findings suggest that most of the observed associations between parental and perinatal factors and risk of stress-related disorders in the population analysis are driven by shared familial environment or genetics, and underscore the importance of family designs in epidemiological studies on the etiology of psychiatric disorders.

Psychobiological stress response to a lung cancer diagnosis: a prospective study of patients in Iceland and Sweden.

BACKGROUND: A diagnostic work-up leading to a lung cancer diagnosis is a severely stressful experience that may impact tumor progression. Yet, prospective data are scarce on psychological and biological components of stress at the time of lung cancer diagnosis. The aim of this study was to assess pre-to-post diagnosis change in psychological distress and urinary excretion of catecholamines in patients with suspected lung cancer. METHODS: Participants were 167 patients within the LUCASS study, recruited at referral for suspected lung cancer to University Hospitals in Iceland and Sweden. Patients completed questionnaires on perceived distress (Hospital Anxiety and Depression Scale, HADS) before and after diagnosis of lung cancer or a non-malignant origin. A subpopulation of 85 patients also provided overnight urine for catecholamine analysis before and at a median of 24 days after diagnosis but before treatment. RESULTS: A lung cancer diagnosis was confirmed in 123 (73.7%) patients, with a mean age of 70.1 years. Patients diagnosed with lung cancer experienced a post-diagnosis increase in psychological distress (p = 0.010), while patients with non-malignant lung pathology showed a reduction in distress (p = 0.070). Both urinary epinephrine (p = 0.001) and norepinephrine (p = 0.032) levels were higher before the diagnosis among patients eventually diagnosed with lung cancer compared to those with non-malignant lung pathology. We observed indications of associations between pre-to-post diagnosis changes in perceived distress and changes in urinary catecholamine levels. CONCLUSION: Receiving a lung cancer diagnosis is associated with an increase in psychological distress, while elevated catecholamine levels are evident already before lung cancer diagnosis.

Association between adverse childhood experiences and perinatal depressive symptoms: a cross-sectional analysis of 16,831 women in Iceland.

Emerging data suggest that certain adverse childhood experiences (ACEs) are associated with perinatal depression (PND). However, few studies have comprehensively assessed the cumulative number and types of ACEs and their association to PND. We conducted a cross-sectional analysis among 16,831 female participants from the Stress-And-Gene-Analysis (SAGA) cohort in Iceland, 2018. ACEs were surveyed with the World Health Organization ACE-International questionnaire, while PND symptoms were assessed using the Edinburgh Postnatal Depression Scale (lifetime version). We, while adjusting for confounding factors, estimated the prevalence ratio (PR) of PND in relation to total number of ACEs using the Poisson quasi-likelihood model and further performed analyses for type-specific ACEs. At a mean age of 44 years (SD ± 11.1), 6,201 (36.8%) participants had experienced probable PND. Total number of ACEs was positively associated with PND (PR 1.11 per ACE, 95% CI: 1.10-1.11), also among women without any psychiatric comorbidities (PR 1.13, 95% CI: 1.11-1.14). PRs increased in a dose-response manner with the number of ACEs (P for trend < 0.001); women that endorsed 5 or more ACEs were twice as likely to have experienced PND (PR 2.24, 95% CI: 2.09-2.41). All ACE types (n = 13) were associated with PND, with most pronounced association for emotional neglect by a guardian (PR 1.53, 95% CI: 1.47-1.59). Our findings suggest a positive association between number of ACEs and PND symptoms. If our results are confirmed with prospective data, healthcare providers need to be alert of the risk of PND among expecting mothers with history of ACEs.

Growth Rate in Childhood and Adolescence and the Risk of Breast and Prostate Cancer: A Population-Based Study.

Growth rate is regulated by hormonal pathways that might affect early cancer development. We explored the association between rate of growth in height from ages 8 to 13 years (childhood) and from age 13 to attainment of adult height (adolescence), as measured at study entry, and the risk of breast or prostate cancer. Participants were 2,037 Icelanders born during 1915-1935, who took part in the Reykjavik Study, established in 1967. Height measurements were obtained from school records and at study entry. We used multivariable Cox regression models to calculate hazard ratios with 95% confidence intervals of breast and prostate cancer by rates of growth in tertiles. During a mean follow-up of 66 years (women) and 64 years (men), 117 women were diagnosed with breast cancer and 118 men with prostate cancer (45 with advanced disease). Women in the highest growth-rate tertile in adolescence had a higher risk of breast cancer (hazard ratio = 2.4, 95% confidence interval: 1.3, 4.3) compared with women in the lowest tertile. A suggestive inverse association was observed for highest adolescent growth rate in men and advanced prostate cancer: hazard ratio = 0.4, 95% confidence interval: 0.2, 1.0. Rapid growth, particularly in adolescence may affect cancer risk later in life.

The role of genetic predisposition in cardiovascular risk after cancer diagnosis: a matched cohort study of the UK Biobank.

BACKGROUND: Evidence is scarce regarding the potential modifying role of disease susceptibility on the association between a prior cancer diagnosis and cardiovascular disease (CVD). METHODS: We conducted a matched cohort study of UK Biobank including 78,860 individuals with a cancer diagnosis between January 1997 and January 2020, and 394,300 birth year and sex individually matched unexposed individuals. We used Cox model to assess the subsequent relative risk of CVD, which was further stratified by individual genetic predisposition. RESULTS: During nearly 23 years of follow-up, an elevated risk of CVD was constantly observed among cancer patients, compared to their matched unexposed individuals. Such excess risk was most pronounced (hazard ratio [HR] = 5.28, 95% confidence interval [CI] 4.90-5.69) within 3 months after a cancer diagnosis, which then decreased rapidly and stabilised for >6 months (HR = 1.22, 95% CI 1.19-1.24). For all the studied time periods, stratification analyses by both levels of polygenic risk score for CVD and by family history of CVD revealed higher estimates among individuals with lower genetic risk predisposition. CONCLUSIONS: Our findings suggest that patients with a recent cancer diagnosis were at an increased risk of multiple types of CVD and the excess CVD risk was higher among individuals with lower genetic susceptibility to CVD, highlighting a general need for enhanced psychological assistance and clinical surveillance of CVD among newly diagnosed cancer patients.

Use of hormonal contraceptives and antidepressants and risks of suicidal behavior and accidents among women with premenstrual disorders: a nationwide cohort study.

BACKGROUND: Women with premenstrual disorders (PMDs) are at increased risks of suicidal behavior and accidents. However, the effect of PMD first-line treatment on such risks have not been assessed. METHODS: To study the association between use of hormonal contraceptives or antidepressants and subsequent risks of suicidal behavior and accidents among women with PMDs. We conducted a nationwide register-based cohort study with between- and within-individual analyses in Sweden. All women with a clinical diagnosis/indication of PMDs recorded in the Patient Register and the Prescribed Drug Register during 1987-2011 were included (n = 23 029, age 15-52 years). Information on hormonal contraceptives and antidepressants prescribed for these women was obtained from the Prescribed Drug Register. Events of suicidal behavior (complete suicide and suicide attempt) and accidents were separately identified through the Patient and the Causes of Death Registers. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of suicidal behavior and accidents after use of hormonal contraceptives or antidepressants were estimated in between-individual and within-individual analyses (i.e., comparing the risk between use and no use in the same individual) using Poisson regression. RESULTS: Women with PMDs were followed for a median of 6.2 years. Compared to no use of hormonal contraceptives, use of hormonal contraceptives was associated with a lower risk of suicidal behavior in both between-individual (IRR 0.76, 0.43-1.34) and within-individual analyses (IRR 0.65, 0.51-0.83). These risk reductions were primarily restricted to combined products (IRR 0.18, 0.07-0.47 and 0.19, 0.08-0.42 in between- and within-individual analyses) and observed among women with/without psychiatric comorbidities (p for interaction 0.830 and 0.043 in between- and within-individual analyses). Yet, the use of hormonal contraceptives was not consistently associated with risk of accidents between between-individual (IRR 1.13, 1.01-1.27) and within-individual analyses (IRR 1.01, 0.92-1.11). Use of antidepressants was associated with a higher risk of suicidal behavior and accidents in both between- and within-individual analyses. CONCLUSIONS: Our findings suggest that use of hormonal contraceptives, particularly combined products, is associated with reduced rates of suicidal behaviors, but not accidents, among women with PMDs. The estimates for antidepressants may be biased by indication.

Genetic predispositions to psychiatric disorders and the risk of COVID-19.

BACKGROUND: Whether a genetic predisposition to psychiatric disorders is associated with coronavirus disease 2019 (COVID-19) is unknown. METHODS: Our analytic sample consisted of 287,123 white British participants in UK Biobank who were alive on 31 January 2020. We performed a genome-wide association study (GWAS) analysis for each psychiatric disorder (substance misuse, depression, anxiety, psychotic disorder, and stress-related disorders) in a randomly selected half of the study population ("base dataset"). For the other half ("target dataset"), the polygenic risk score (PRS) was calculated as a proxy of individuals' genetic predisposition to a given psychiatric phenotype using discovered genetic variants from the base dataset. Ascertainment of COVID-19 was based on the Public Health England dataset, inpatient hospital data, or death registers in UK Biobank. COVID-19 cases from hospitalization records or death records were considered "severe cases." The association between the PRS for psychiatric disorders and COVID-19 risk was examined using logistic regression. We also repeated PRS analyses based on publicly available GWAS summary statistics. RESULTS: A total of 143,562 participants (including 10,868 COVID-19 cases) were used for PRS analyses. A higher genetic predisposition to psychiatric disorders was associated with an increased risk of any COVID-19 and severe COVID-19. The adjusted odds ratio (OR) for any COVID-19 was 1.07 (95% confidence interval [CI] 1.02-1.13) and 1.06 (95% CI 1.01-1.11) among individuals with a high genetic risk (above the upper tertile of the PRS) for substance misuse and depression, respectively, compared with individuals with a low genetic risk (below the lower tertile). Slightly higher ORs were noted for severe COVID-19, and similar result patterns were obtained in analyses based on publicly available GWAS summary statistics. CONCLUSIONS: Our findings suggest a potential role of genetic factors in the observed phenotypic association between psychiatric disorders and COVID-19. Our data underscore the need for increased medical surveillance for this vulnerable population during the COVID-19 pandemic.

Dietary patterns in adolescence and risk of colorectal cancer: a population-based study.

PURPOSE: To study whether dietary patterns in adolescence are associated with risk of colorectal cancer (CRC). METHODS: Food frequency data were obtained from the AGES-Reykjavik study, conducted between 2002 and 2006, which included 5,078 (58% women) participants with mean age of 77 (± 5.8) years. Principal component analysis was used to identify dietary patterns. Participants were followed through linkage to the Icelandic Cancer Registry. Multivariable Cox models were used to calculate hazard ratios (HR) of CRC and 95% confidence interval (CI) by dietary patterns. RESULTS: During the follow-up period (mean 8.2 years), 136 participants (75 women and 61 men) were diagnosed with CRC. The main dietary pattern in adolescence was characterized by high intake of traditional food items consumed in the earlier half of the twentieth century, namely, salted or smoked meat and fish, milk, offal, rye bread, and oatmeal. Compared to the lowest tertile, the middle tertile of this pattern was associated with increased risk of CRC (HR 1.63, 95% CI 1.04-2.57), while the highest tertile was not statistically associated with CRC (HR 1.48, 95% CI 0.93-2.37), except among women (HR 2.06, 95% CI 1.11-3.84). CONCLUSION: These data suggest that strong adherence to a traditional Icelandic diet in adolescence might increase the risk of CRC, particularly among women. More research is need on the association between food items and dietary patterns of relevance to CRC at different points in the life cycle.

Neuroendocrine pathways and breast cancer progression: a pooled analysis of somatic mutations and gene expression from two large breast cancer cohorts.

BACKGROUND: Experimental studies indicate that neuroendocrine pathways might play a role in progression of breast cancer. We aim to test the hypothesis that somatic mutations in the genes of neuroendocrine pathways influence breast cancer prognosis, through dysregulated gene expression in tumor tissue. METHODS: We conducted an extreme case-control study including 208 breast cancer patients with poor invasive disease-free survival (iDFS) and 208 patients with favorable iDFS who were individually matched on molecular subtype from the Breast Cancer Cohort at West China Hospital (WCH; N = 192) and The Cancer Genome Atlas (TCGA; N = 224). Whole exome sequencing and RNA sequencing of tumor and paired normal breast tissues were performed. Adrenergic, glucocorticoid, dopaminergic, serotonergic, and cholinergic pathways were assessed for differences in mutation burden and gene expression in relation to breast cancer iDFS using the logistic regression and global test, respectively. RESULTS: In the pooled analysis, presence of any somatic mutation (odds ratio = 1.66, 95% CI: 1.07-2.58) of the glucocorticoid pathway was associated with poor iDFS and a two-fold increase of tumor mutation burden was associated with 17% elevated odds (95% CI: 2-35%), after adjustment for cohort membership, age, menopausal status, molecular subtype, and tumor stage. Differential expression of genes in the glucocorticoid pathway in tumor tissue (P = 0.028), but not normal tissue (P = 0.701), was associated with poor iDFS. Somatic mutation of the adrenergic and cholinergic pathways was significantly associated with iDFS in WCH, but not in TCGA. CONCLUSION: Glucocorticoid pathway may play a role in breast cancer prognosis through differential mutations and expression. Further characterization of its functional role may open new avenues for the development of novel therapeutic targets for breast cancer.

Public awareness, emotional reactions and human mobility in response to the COVID-19 outbreak in China - a population-based ecological study.

BACKGROUND: The outbreak of COVID-19 generated severe emotional reactions, and restricted mobility was a crucial measure to reduce the spread of the virus. This study describes the changes in public emotional reactions and mobility patterns in the Chinese population during the COVID-19 outbreak. METHODS: We collected data on public emotional reactions in response to the outbreak through Weibo, the Chinese Twitter, between 1st January and 31st March 2020. Using anonymized location-tracking information, we analyzed the daily mobility patterns of approximately 90% of Sichuan residents. RESULTS: There were three distinct phases of the emotional and behavioral reactions to the COVID-19 outbreak. The alarm phase (19th-26th January) was a restriction-free period, characterized by few new daily cases, but a large amount public negative emotions [the number of negative comments per Weibo post increased by 246.9 per day, 95% confidence interval (CI) 122.5-371.3], and a substantial increase in self-limiting mobility (from 45.6% to 54.5%, changing by 1.5% per day, 95% CI 0.7%-2.3%). The epidemic phase (27th January-15th February) exhibited rapidly increasing numbers of new daily cases, decreasing expression of negative emotions (a decrease of 27.3 negative comments per post per day, 95% CI -40.4 to -14.2), and a stabilized level of self-limiting mobility. The relief phase (16th February-31st March) had a steady decline in new daily cases and decreasing levels of negative emotion and self-limiting mobility. CONCLUSIONS: During the COVID-19 outbreak in China, the public's emotional reaction was strongest before the actual peak of the outbreak and declined thereafter. The change in human mobility patterns occurred before the implementation of restriction orders, suggesting a possible link between emotion and behavior.

Disease trajectories and mortality among individuals diagnosed with depression: a community-based cohort study in UK Biobank.

Patients with depression are at increased risk for a range of comorbid diseases, with, however, unclear explanations. In this large community-based cohort study of the UK Biobank, 24,130 patients diagnosed with depression were compared to 120,366 matched individuals without such a diagnosis. Follow-up was conducted from 6 months after the index date until death or the end of 2019, for the occurrence of 470 medical conditions and 16 specific causes of death. The median age at the time of the depression diagnosis was 62.0 years, and most of the patients were female (63.63%). During a median follow-up of 4.94 years, 129 medical conditions were found to be significantly associated with a prior diagnosis of depression, based on adjusted Cox regression models. Using disease trajectory network analysis to visualize the magnitude of disease-disease associations and the temporal order of the associated medical conditions, we identified three main affected disease clusters after depression (i.e., cardiometabolic diseases, chronic inflammatory diseases, and diseases related to tobacco abuse), which were further linked to a wider range of other conditions. In addition, we also identified three depression-mortality trajectories leading to death due to cardiovascular disease, respiratory system disease and malignant neoplasm. In conclusion, an inpatient diagnosis of depression in later life is associated with three distinct network-based clusters of medical conditions, indicating alterations in the cardiometabolic system, chronic status of inflammation, and tobacco abuse as key pathways to a wide range of other conditions downstream. If replicated, these pathways may constitute promising targets for the health promotion among depression patients.

Stress-related disorders and subsequent cancer risk and mortality: a population-based and sibling-controlled cohort study in Sweden.

Prior research has suggested a potential role of psychological stress on cancer development while the role of familial factors on this association is underexplored. We conducted a nationwide cohort study including 167,836 individuals with a first-onset stress-related disorder (including post-traumatic stress disorder, acute stress reaction, adjustment disorder and other stress reactions) diagnosed between 1981 and 2016 in Sweden (i.e., exposed patients), 1,631,801 birth year- and sex-matched unexposed individuals, and 179,209 unaffected full siblings of the exposed patients. Cox models were used to estimate the hazard ratios (HRs) of newly diagnosed cancer and cancer-related death, beyond 1 year after diagnosis of stress-related disorders. We further examined the potential mediation roles of behavior-related morbidities in the associations of stress-related disorders with smoking or alcohol-related cancer incidence and mortality. We found modestly elevated risks of cancer incidence and mortality among exposed patients compared with matched unexposed individuals (incidence: HR = 1.03, 95% CI 1.01-1.06; mortality: HR = 1.13, 95% CI 1.07-1.18), while not when comparing with full siblings (incidence: HR = 1.03, 95% CI 0.99-1.08; mortality: HR = 1.09, 95% CI 1.00-1.19). Similarly, the suggested elevations in incidence and mortality of individual cancer sites (or groups) in the population-based comparison attenuated towards null in the between-sibling comparison. The risk elevations for smoking or alcohol-related cancers in the population-based comparison (incidence: HR = 1.18, 95% CI 1.11-1.24; mortality: HR = 1.20, 95% CI 1.12-1.29) were partially mediated by alcohol-related morbidities during follow-up. Collectively, our findings suggest that the association between stress-related disorders and cancer risk and mortality is largely explained by familial factors, including shared behavioral hazards.

Optimal communication associated with lower risk of acute traumatic stress after lung cancer diagnosis.

PURPOSE: The aim of this study was to assess the role of the patient's background and perceived healthcare-related factors in symptoms of acute stress after lung cancer diagnosis. METHODS: The study population consisted of 89 individuals referred for diagnostic work-up at Landspitali National University Hospital in Iceland and subsequently diagnosed with lung cancer. Before diagnosis, the patients completed questionnaires on sociodemographic characteristics, pre-diagnostic distress (Hospital Anxiety and Depression Scale), social support, and resilience. At a median of 16 days after diagnosis, the patients reported symptoms of acute stress on the Impact of Event Scale-Revised (IES-R) and experience of communication and support from healthcare professionals and family during the diagnostic period. RESULTS: Patients were on average 68 years and 52% reported high levels of post-diagnostic acute stress (IES-R > 23) while 24% reported symptoms suggestive of clinical significance (IES-R > 32). Prior history of cancer (ß = 6.7, 95% CI: 0.1 to 13.3) and pre-diagnostic distress were associated with higher levels of post-diagnostic acute stress (ß = 8.8, 95% CI: 2.7 to 14.9), while high educational level (ß = - 7.9, 95% CI: - 14.8 to - 1.1) was associated with lower levels. Controlling for the abovementioned factors, the patients' perception of optimal doctor-patient (ß = - 9.1, 95% CI: - 14.9 to - 3.3) and family communication (ß = - 8.6, 95% CI: - 14.3 to - 2.9) was inversely associated with levels of post-diagnostic acute stress after lung cancer diagnosis. CONCLUSIONS: A high proportion of patients with newly diagnosed lung cancer experience high levels of acute traumatic stress of potential clinical significance. Efforts to improve doctor-patient and family communication may mitigate the risk of these adverse symptoms.

Public health insurance and cancer-specific mortality risk among patients with breast cancer: A prospective cohort study in China.

Little is known about how health insurance policies, particularly in developing countries, influence breast cancer prognosis. Here, we examined the association between individual health insurance and breast cancer-specific mortality in China. We included 7436 women diagnosed with invasive breast cancer between 2009 and 2016, at West China Hospital, Sichuan University. The health insurance plan of patient was classified as either urban or rural schemes and was also categorized as reimbursement rate (ie, the covered/total charge) below or above the median. Breast cancer-specific mortality was the primary outcome. Using Cox proportional hazards models, we calculated hazard ratios (HRs) for cancer-specific mortality, contrasting rates among patients with a rural insurance scheme or low reimbursement rate to that of those with an urban insurance scheme or high reimbursement rate, respectively. During a median follow-up of 3.1 years, we identified 326 deaths due to breast cancer. Compared to patients covered by urban insurance schemes, patients covered by rural insurance schemes had a 29% increased cancer-specific mortality (95% CI 0%-65%) after adjusting for demographics, tumor characteristics and treatment modes. Reimbursement rate below the median was associated with a 42% increased rate of cancer-specific mortality (95% CI 11%-82%). Every 10% increase in the reimbursement rate is associated with a 7% (95% CI 2%-12%) reduction in cancer-specific mortality risk, particularly in patients covered by rural insurance schemes (26%, 95% CI 9%-39%). Our findings suggest that underinsured patients face a higher risk of breast cancer-specific mortality in developing countries.