The association between stress and cancer incidence has been studied for more than seven decades. Despite plausible biological mechanisms and evidence from laboratory studies, findings from clinical research are conflicting. The objective of this study was to examine the association between PTSD and various cancer outcomes. This nation-wide cohort study included all Danish-born residents of Denmark from 1995 to 2011. The exposure was PTSD diagnoses (n = 4131). The main outcomes were cancer diagnoses including: (1) all malignant neoplasms; (2) hematologic malignancies; (3) immune-related cancers; (4) smoking- and alcohol-related cancers; (5) cancers at all other sites. Standardized incidence ratios (SIR) were calculated. Null associations were found between PTSD and nearly all cancer diagnoses examined, both overall [SIR for all cancers = 1.0, 95 % confidence interval (CI) = 0.88, 1.2] and in analyses stratified by gender, age, substance abuse history and time since PTSD diagnosis. This study is the most comprehensive examination to date of PTSD as a predictor of many cancer types. Our data show no evidence of an association between PTSD and cancer in this nationwide cohort.

Background

Posttraumatic stress disorder is a well-documented risk factor for cardiovascular disease. Whether non-specific stress-related psychopathology also increases risk is less well known.

Methods

In a cohort of adult Danish-born residents of Denmark with an incident diagnosis of unspecified reaction to severe stress ("unspecified stress reaction") between 1995 and 2011 (N = 24,534), we assessed incidence of seven arterial and venous cardiovascular events/conditions between 1996 and 2013. We calculated standardized incidence ratios (SIRs) comparing incidence of each outcome among the cohort to expected incidence based on sex-, age-, and calendar-time-specific national rates. We conducted stratified analyses by demographic characteristics, comorbidities, and length of follow-up time.

Results

Incidence over the study period ranged from 1.1% for provoked VTE to 5.7% for stroke, adjusting for competing risk of death. Unspecified stress reaction was associated with all outcomes (SIRs ranging from 1.3, 95% confidence interval (CI): 1.1-1.4 for atrial fibrillation/flutter to 1.9, 95% CI: 1.7-2.2 for unprovoked VTE and 1.9, 95% CI: 1.6-2.3 for provoked VTE). Associations persisted, but were attenuated, when restricting to persons without alcohol use disorder and to persons without physical health comorbidities.

Limitations

Unspecified stress reaction has less precise criteria than other stress-related diagnoses, and we could not adjust for some potential confounders.

Conclusions

Our results augment literature on stress disorders and cardiovascular disease by highlighting the additional importance of unspecified stress disorders. Further research on this diagnostic category, which may represent subsyndromal psychopathology, is warranted. These findings support considering persons with non-specific stress-related psychopathology in treatment and tertiary prevention activities.

OBJECTIVE:There is some evidence that posttraumatic stress disorder (PTSD) is associated with increased risk of infections, and it is unknown whether adjustment disorder is as well. We assessed the association between adjustment disorder and subsequent infections, and assessed additive interaction with sex. METHODS:The study population included a nationwide cohort of all Danish-born residents of Denmark diagnosed with adjustment disorder between 1995 and 2011, and an age- and sex-matched general population comparison cohort. We compared rates of infections requiring inpatient or outpatient hospitalization in the two cohorts. We fit Cox proportional hazards models to compute adjusted hazard ratios (aHR) for the associations between adjustment disorder and 32 types of infections, and calculated interaction contrasts to assess interaction between adjustment disorder and sex. RESULTS:Adjustment disorder was associated with increased rates of infections overall (n = 19,838 infections, aHR = 1.8, 95% confidence interval = 1.8. 1.9), and increased rates of each individual infection type (aHRs for 30 infections ranged from 1.5 to 2.3), adjusting for baseline psychiatric and somatic comorbidities and marital status. For many infection types (e.g., skin infections, pneumonia), interaction contrasts indicated rate differences were greater among men than women, while for two (urinary tract infections and sexually transmitted infections), rate differences were greater for women. CONCLUSIONS:These findings are consistent with studies examining the relationship between psychological stress and infections, and between PTSD and infections. They may be explained by a combination of the triggering of unhealthy behaviors as well as immune responses to stress.

There is an association between stress and dementia. However, less is known about dementia among persons with varied stress responses and sex differences in these associations. We used this population-based cohort study to examine dementia among persons with a range of clinician-diagnosed stress disorders, as well as the interaction between stress disorders and sex in predicting dementia, in Denmark from 1995 to 2011. This study included Danes aged 40 years or older with a stress disorder diagnosis (n = 47,047) and a matched comparison cohort (n = 232,141) without a stress disorder diagnosis with data from 1995 through 2011. Diagnoses were culled from national registries. We used Cox proportional hazards regression to estimate associations between stress disorders and dementia. Risk of dementia was higher for persons with stress disorders than for persons without such diagnosis; adjusted hazard ratios ranged from 1.6 to 2.8. There was evidence of an interaction between sex and stress disorders in predicting dementia, with a higher rate of dementia among men with stress disorders except posttraumatic stress disorder, for which women had a higher rate. Results support existing evidence of an association between stress and dementia. This study contributes novel information regarding dementia risk across a range of stress responses, and interactions between stress disorders and sex.

Residential clusters of non-communicable diseases are a source of enduring public concern, and at times, controversy. Many clusters reported to public health agencies by concerned citizens are accompanied by expectations that investigations will uncover a cause of disease. While goals, methods and conclusions of cluster studies are debated in the scientific literature and popular press, investigations of reported residential clusters rarely provide definitive answers about disease etiology. Further, it is inherently difficult to study a cluster for diseases with complex etiology and long latency (e.g., most cancers). Regardless, cluster investigations remain an important function of local, state and federal public health agencies. Challenges limiting the ability of cluster investigations to uncover causes for disease include the need to consider long latency, low statistical power of most analyses, uncertain definitions of cluster boundaries and population of interest, and in- and out-migration. A multi-disciplinary Workshop was held to discuss innovative and/or under-explored approaches to investigate cancer clusters. Several potentially fruitful paths forward are described, including modern methods of reconstructing residential history, improved approaches to analyzing spatial data, improved utilization of electronic data sources, advances using biomarkers of carcinogenesis, novel concepts for grouping cases, investigations of infectious etiology of cancer, and "omics" approaches.