Stress-related Diagnoses Research Articles

Sick-leave trajectories among people sickness absent with stress-related diagnoses; cohort studies

Abstract Background Stress-related disorders are common sickness absence (SA) diagnoses in many Western countries. Knowledge of SA and disability pension (DP) patterns among people with such SA is needed. Thus, the aim was to identify future SADP trajectories among people with a new SA spell due to stress-related diagnosis and to examine sociodemographic and health-related factors associated with identified trajectories. Methods Using microdata from nationwide registers, we included all people living in Sweden with a new SA spell >14 days due to stress-related diagnoses (ICD-10 code F43) in 2011 (N = 32,417) or 2018 (N = 65,511), respectively. These two cohorts were followed prospectively for 13 months from the SA spell start, to identify trajectory groups of mean SA/DP days/month using group-based trajectory modeling. We used multinomial logistic regression to explore associations between sociodemographic and health-related predictors and trajectory membership. Results We identified the following SA/DP trajectories in both cohorts: steep drop (30.6% and 35.9% of all included in 2018 and 2011, respectively); fluctuating (8.7%, 11.2%); fast decrease (25.5%, 24.4%); medium decrease (18.1%, 13.1%); slow decrease (10.8%, 7.3%), and constant high (6.2%, 8.0%). Compared to the steep drop trajectory, individuals in the other trajectories were more likely women, older, and had prior SA/DP or secondary outpatient healthcare visits. Starting the SA spell full-time was the strongest predictor for the slow decrease and constant high trajectory, and previous SA or diagnosis of other mental disorders were predictors of the constant fluctuating and constant high trajectory. Conclusions The similarity of the identified trajectories in the two cohorts is a strength. The results reveal the diversity of future SA/DP in this patient group, indicating the importance of identifying patients at risk of long-term SA who might need further interventions early in the process. Key messages • In two population-wide cohorts with a new sickness absence (SA) spell with stress-related diagnoses, six trajectories of SA/disability pension days were identified during the 13-month follow-up. • Most of those in the cohorts had trajectories that ended with no SA/DP after 13 months, while two trajectories, including 15-19% of individuals, showed high or varying SA/DP days during the follow-up.

Sickness absence duration of stress complaints, adaptation disorder or burnout in the Netherlands

Abstract In the Netherlands, occupational physicians can diagnose burnout when employees report sick. Their guideline distinguishes between stress complaints lasting < 3 months, adaptation disorder with complaints lasting 3-6 months and burnout with complaints lasting > 6 months at moment of diagnosis. The Four-Dimensional Symptom Questionnaire (4DSQ) is recommended to assess and monitor. The new Burnout Assessment Tool (BAT) might be an alternative. Research questions were: 1) What are the sickness absence duration, 4DSQ and BAT-scores of absentees diagnosed with stress complaints, adaptation disorder and burnout?; 2) Is the BAT a better predictor of sickness absence duration than the 4DSQ? From 2020-2023, data was collected among all 3,462 employees who were absent due to stress complaints, adaptation disorder or burnout at one large occupational health and safety service via registry data and an employee questionnaire. Results show that two-thirds of those with stress complaints, half of them with adaptation disorder and one third with burnout were absent for less than half a year. 4DSQ and BAT scores differed significantly between the three groups (p<.05). The BAT explained 0.8% of variance in absence duration (p< .001) when controlled for covariates, which explained 1.6% of variance (p< .001). The explanation by BAT was 1.9% within the group with stress complaints (p = 0.002), .4% within the group with adaptation disorder (p=.022) and absent within the group with burnout. Comparable results were found for the 4DSQ. The differences in absence duration between the three groups aligned with the Dutch guidelines. The BAT nor the 4DSQ were clinically relevant predictors of duration of absence for stress-related diagnoses among absentees in the Netherlands. To reduce productivity loss, it seems better to report sick when still in the stage of stress complaints than to wait until a full burnout has developed. The BAT and 4DSQ might help risk assessment in the working population. Key messages • The sickness absence duration of Dutch employees diagnosed with burnout is much longer than that of those with adaptation disorder or stress complaints. • Both the instrument recommended in the guideline and the new instrument have no clinical relevance in predicting sickness absence duration of stress-related diagnoses.

Sickness absence after work accidents and post-traumatic stress among white-collar workers in the retail and wholesale industry; a longitudinal Swedish cohort study

BackgroundMost studies about accidents and about PTSD, respectively, have been conducted either on blue-collar workers, or on the entire working population. There are very few such studies on white-collar workers.AimTo examine diagnosis-specific sickness absence (SA) and disability pension (DP) after a work accident or PTSD, respectively, among white-collar workers in the private retail and wholesale industry.MethodsA prospective population-based cohort study of all 192,077 such workers aged 18–67 (44% women) in Sweden in 2012, using linked microdata from nationwide registers. We identified individuals who had secondary healthcare due to work-related accidents (n = 1114; 31% women) or to PTSD (n = 216; 79% women) in 2012–2016. Their average number of net days of diagnosis-specific SA (in SA spells > 14 days) and DP were calculated for 365 days before and 365 days after the healthcare visit.Results35% of the women and 24% of the men had at least one new SA spell during the 365 days after healthcare due to work accidents. Among women, the average number of SA/DP days increased from 14 in the year before the visit to 31 days the year after; among men from 9 to 21 days. SA days due to fractures and other injuries increased most, while SA days due to mental diagnoses increased somewhat. 73% of women and 64% of men who had healthcare due to PTSD had at least one new SA spell in the next year. Women increased from 121 to 157 SA/DP days and men from 112 to 174. SA due to stress-related disorders and other mental diagnoses increased the most, while DP due to stress-related diagnoses and SA due to musculoskeletal diagnoses increased slightly.ConclusionsAbout a quarter of those who had secondary healthcare due to work accidents, and the majority of those with such healthcare due PTSD, had new SA in the following year. SA due to injury and mental diagnoses, respectively, increased most, however, SA/DP due to other diagnoses also increased slightly. More knowledge is needed on factors associated with having or not having SA/DP in different diagnoses after work accidents and among people with PTSD.

Sickness absence after work injuries and post-traumatic stress among white-collar workers

Abstract Background There is very little knowledge about sickness absence (SA) and disability pension (DP) after work injuries and post-traumatic stress disorder (PTSD) among white collar workers. The aim was to examine diagnosis-specific SA and DP after healthcare due to a workplace injury and PTSD, respectively, among white-collar workers in the wholesale and retail industry in Sweden. Methods A prospective population-based cohort study of all 192,077 such white-collar workers (44% women) in Sweden in 2012, using linked microdata from three nationwide registers covering 2012-2016. We identified individuals who had specialised out- or inpatient healthcare due to a work injury (n = 1114) or to PTSD (n = 216) in the years 2012-2016. Their average number of net days of diagnosis-specific SA and DP was calculated for the 365 days before and 365 days after the healthcare visit. Results 64% of women and 45% of the men had at least one new SA spell during the 365 days after healthcare due to a work injury. On average, women had 14 SA/DP days the year before the injury and 31 days after; corresponding days for men were 9 and 21 days. SA days with fractures and with other injuries increased most, while SA days with mental diagnoses increased slightly. In the PTSD group, 80% of women and 65% of men had a new SA spell. Women's SA/DP days increased from 121 to 157 and men's from 112 to 174. SA with stress-related disorders and other mental diagnoses increased most, while DP with stress-related diagnoses and SA with musculoskeletal diagnoses increased slightly. Conclusions About half of those who had healthcare due to work injuries, and the majority of those who had PTSD, had new SA following the healthcare. SA due to diagnoses related to injury and mental diagnoses, respectively, increased most, however, SA/DP days due to other diagnoses also increased slightly. More knowledge is needed on factors associated with having or not having SA/DP with different diagnoses after work injuries and PTSD. Key messages • About half of those who had specialised healthcare due to work injuries, and the majority of those who had PTSD, had new SA in the following 365 days. • Individuals with healthcare for PTSD had more SA/DP days both before and after their healthcare visit than those with work injuries, but individuals with work injuries had a larger increase.

Psychological well-being of patients with arthritis: impact of psychological distress on quality of life, and patient satisfaction

BACKGROUND & OBJECTIVE: Arthritis is an autoimmune disease in which individual’s immune system attack healthy cells in one’s body and giving rise to inflammation. Recently, it has been found to be manifested in individuals with stress-related diagnosis. This study investigates how psychological distress, quality of life, patient satisfaction, and the role of pharmacists affect the psychological well-being of patients who have received medical diagnoses of different forms of arthritis.
 METHODOLOGY: This cross-sectional study was conducted at the Department of Psychology University of Gujrat during 1st January to 30th August, 2022. A sample of 380 patients already diagnosed with arthritis by the physicians was taken by Purposive sampling technique, from various orthopedic hospitals. A demographic sheet, and Urdu versions of Depression, Anxiety, Stress Scale DASS-21, WHO QOL-BREF, Patient Satisfaction with Pharmacist Services Questionnaire and Flourishing Scale were used to assess psychological distress, quality of life, doctor patient satisfaction and psychological well-being in arthritis patients.
 RESULTS: The study results showed that there is a significant negative correlation between quality of life and psychological distress (r= -.11, p<0.01). Well-being and quality of life are positively correlated (r=.68, p<0.01). 57% variance in wellbeing of the patients with arthritis is explainable due to the presence of psychological distress, and perceived quality of life.
 CONCLUSION: The well-being of individuals diagnosed with arthritis can be strongly predicted by their levels of psychological distress and their perceived quality of life. This study delves into the implications of these findings.

Does employer involvement in primary health care enhance return to work for patients with stress-related mental disorders? a cluster randomized controlled trial

BackgroundStress-related disorders have become a major challenge for society and are associated with rising levels of sick leave. The provision of support to facilitate the return to work (RTW) for this patient group is of great importance. The aim of the present study was to evaluate whether a new systematic procedure with collaboration between general practitioners (GPs), rehabilitation coordinators (RCs) and employers could reduce sick leave days for this patient group.MethodEmployed patients with stress-related diagnoses seeking care at primary health care centres (PHCCs) were included in either the intervention group (n = 54), following the systematic intervention procedure, or the control group (n = 58), receiving treatment as usual (TAU). The intervention included a) a training day for participant GPs and RCs, b) a standardised procedure for GPs and RCs to follow after training, c) the opportunity to receive clinical advice from specialist physicians in the research group. Outcome measures for RTW were sick leave days.ResultsThe median number of registered gross sick leave days was lower for the control group at six, 12 and 24 months after inclusion, but the difference was not statistically significant. The control group had significantly fewer net sick leave days at three months (p = 0.03) at six months (p = 0.00) and at 12-months follow-up (p = 0.01). At 24 months, this difference was no longer significant.ConclusionsThe PRIMA intervention, which applied a standardized procedure for employer involvement in the rehabilitation process for patients with stress-related disorders, actually increased time to RTW compared to TAU. However, at 24 months, the benefit of TAU could no longer be confirmed. The study was registered on 16/01/2017 (ClinicalTrials.gov, NCT03022760).

Psychometric and structural properties of the Karolinska Exhaustion Disorder Scale: a 1,072-patient study

ObjectiveExhaustion disorder is a stress-related diagnosis that was introduced in 2005 to the Swedish version of the International Statistical Classification of Diseases and Related Health Problems, 10th edition (ICD-10). The Karolinska Exhaustion Disorder Scale (KEDS) was developed to assess exhaustion disorder symptomatology. While the KEDS is intended to reflect a single construct and be used based on its total score, the instrument's characteristics have received limited attention. This study investigated the KEDS’s psychometric and structural properties in a large clinical sample.MethodsThe study relied on data from 1,072 patients diagnosed with exhaustion disorder that were included in two clinical trials in Sweden. We investigated the dimensionality, homogeneity, and reliability of the KEDS using advanced statistical techniques, including exploratory structural equation modeling (ESEM) bifactor analysis.ResultsA one-factor confirmatory analytic model exhibited a poor fit, suggesting at least a degree of multidimensionality. The ESEM bifactor analysis found the general factor to explain about 72% of the common variance extracted, with an omega hierarchical coefficient of 0.680. Thus, the ESEM bifactor analysis did not clearly support the scale’s essential unidimensionality. A homogeneity analysis revealed a scale-level H of only 0.296, suggesting that KEDS’s total scores do not accurately rank individuals on the latent continuum assumed to underlie the measure. The KEDS’s reliability was modest, signaling considerable measurement error.ConclusionFindings reveal important limitations to the KEDS with possible implications for the status of exhaustion disorder as a nosological category.Trial registrationThis study was pre-registered on Open Science Framework (osf.io) on April 24, 2022 (https://osf.io/p34sq/).

Domestic Factors as Determinant of Sickness Absence with Psychiatric Disorders: A Scoping Review of Nordic Research Published between 2010-2019.

Uneven division of domestic factors may contribute to sex differences in sickness absence with psychiatric disorders. The aim of this scoping review was to compile current Nordic research on domestic factors and sickness absence with psychiatric disorders. A systematic search was performed to identify studies from the Nordic countries published between 1 January 2010 and 31 December 2019. Twelve studies were included. Marital status, family situation, work-home interference (in both directions), social affiliation, and loss of child/young adult (suicide, accident, or natural death) were identified as measures of domestic factors. In 8 of the 12 studies, domestic factors were used as co-variates, while four used them as the main exposure. Social affiliation, home-to-work conflict, and total workload were not associated with the outcome. One study found that parents with children older than two years, widows/widowers, and those divorced or unmarried had an increased risk of sickness absence with psychiatric disorders. One study found that work-to-home conflict was associated with sickness absence with stress-related diagnoses in men, and with other mental disorders in women. Finally, one study found that losing a son or daughter aged 16-24 years increased the risk of future sickness absence with a psychiatric disorder regardless of the cause of death. Future studies need to develop concepts, study designs, and measurements to move this research area further. In particular, the concept of "unpaid domestic work" needs theoretical and empirical development.

Exhaustion disorder: scoping review of research on a recently introduced stress-related diagnosis - ERRATUM.

Exhaustion disorder: scoping review of research on a recently introduced stress-related diagnosis - ERRATUM.

Exhaustion disorder: scoping review of research on a recently introduced stress-related diagnosis.

Symptoms related to chronic stress are prevalent and entail high societal costs, yet there is a lack of international consensus regarding diagnostics and treatment. A new stress-related diagnosis, exhaustion disorder, was introduced into the Swedish version of ICD-10 in 2005. Since then, use of the diagnosis has increased rapidly. To create the first comprehensive synthesis of research on exhaustion disorder to report on the current state of knowledge. Preregistration: Open Science Framework (http://www.w3.org/1999/xlink">osf.io), doi 10.17605/OSF.IO/VFDKW. A PRISMA-guided scoping review of all empirical studies of exhaustion disorder was conducted. Searches were run in the MEDLINE, PsycInfo and Web of Science databases. Data were systematically charted and thematically categorised based on primary area of investigation. Eighty-nine included studies were sorted into six themes relating to lived experience of exhaustion disorder (n = 9), symptom presentation and course (n = 13), cognitive functioning (n = 10), biological measures (n = 24), symptom measurement scales (n = 4) and treatment (n = 29). Several studies indicated that individuals with exhaustion disorder experience a range of psychiatric and somatic symptoms beyond fatigue, but robust findings within most thematic categories were scarce. The limited number of studies, lack of replication of findings and methodological limitations (e.g. small samples and scarcity of specified primary outcomes) preclude firm conclusions about the diagnostic construct. More research is needed to build a solid knowledge base for exhaustion disorder. International collaboration regarding the conceptualisation of chronic stress and fatigue is warranted to accelerate the growth of evidence.

Preexisting stress-related diagnoses and mortality: A Danish cancer cohort study.

This study evaluated the association between preexisting stress-related diagnoses and mortality in a Danish population-based cancer cohort. This study included Danish patients with cancer diagnosed in 1995-2011 who had a stress-related diagnosis before their cancer diagnosis. Cancer patients without a prior stress-related diagnosis were matched 5:1 to the stress disorder cohort by cancer site, age group, calendar period, and sex. The 5-year cumulative incidence of cancer-specific and all-cause mortality was computed by stress-related diagnosis category. Hazard ratios and 95% confidence intervals (CIs) associating stress-related diagnoses with mortality were computed by follow-up time, stress-related diagnosis category, stage, comorbidity status, and cancer type. This study identified 4437 cancer patients with a preexisting stress-related diagnosis and 22,060 matched cancer cohort members. The 5-year cumulative risk of cancer-specific mortality was 33% (95% CI, 32%-35%) for those with a preexisting stress-related diagnosis and 29% (95% CI, 28%-29%) for those without a prior stress-related diagnosis. Cancer patients with a preexisting stress-related diagnosis had a 1.3 times higher cancer-specific mortality rate than the comparison cohort members (95% CI, 1.2-1.5). This increase persisted across categories of stress-related diagnosis. The association varied by stage and cancer type, with more pronounced associations found among those with a late stage at diagnosis and hematological malignancies. Cancer patients with preexisting stress-related diagnoses had increased rates of cancer-specific and all-cause mortality. The results suggest that psychiatric comorbidities may be an important consideration for cancer prognosis, and cancer treatment informed by a patient's history may improve outcomes.

Enhancing credibility: A qualitative study of being on sick leave with a stress-related psychiatric diagnosis

In the Western world mental health problems are increasing and in Sweden these problems are the most common reason for sick leave. Diagnoses of adjustment disorders and reactions to severe stress are increasing the fastest out of all mental health problems. The aim of this study is to contribute new insights into employees’ experiences and management of being on sick leave with a stress-related psychiatric diagnosis. The empirical material consisted of individual interviews with 26 employees who were on sick leave from at least part-time employment because of a stress-related diagnosis. The grounded theory method was used to analyse the results. In the generated model, we propose that sick-listed employees engage in enhancing credibility in relation to themselves and others, here attempting to come across as credible and, thus, avoiding disbelief and the negative attributions of being on sick leave with a psychiatric diagnosis. The interviewees shared the general concern that being perceived as either healthier or sicker than the case may be, as well as greater sensitivity to what others might think, which was manifested as being on guard and controlling their behaviour and emotional display. To return to work, the sick-listed employees tended to re-evaluate their previous performance at work and saw the illness as self-inflicted and as the result of not having been capable of drawing the line between work and leisure.

Unjust: the health records of youth with personal/family justice involvement in a large pediatric health system

BackgroundMass incarceration has had an undeniable toll on childhood poverty and inequality, however, little is known about the consequences on pediatric health. The purpose of this study was to identify and describe the health of pediatric patients with probable personal or family history involvement with the correctional system.MethodsA descriptive study was conducted using electronic health record data of 2.3 million youth (ages 0–21 years) who received care in a large Midwestern hospital-based institution from February 2006–2020. We employed a correctional-related keyword search (e.g. jail, prison, probation, parole) to locate youth with probable personal or family history involvement. Health characteristics were measured as clinician diagnostic codes.ResultsTwo percent of the total pediatric population had a correctional keyword in the medical chart (N = 51,855). This 2% made up 66% of all patients with cannabis-related diagnoses, 52% of all patients with trauma-related diagnoses, 48% of all stress-related diagnoses, 38% of all patients with psychotic disorder diagnoses, and 33% of all suicidal-related disorders within this institution’s electronic health record database – among other highly concerning findings.ConclusionsWe captured an alarming health profile that warrants further investigation and validation methods to better address the gaps in our clinical understanding of youth with personal or family history involvement with the correctional system. We can do better in identifying, and supporting families affected by the correctional system.

Somatic symptoms and associations with common psychological diagnoses: a retrospective cohort study from Norwegian urban general practice.

Patients with mental health problems often present with somatic symptoms when visiting their general practitioner (GP). Somatic presentations may challenge correct diagnosing of mental health disorders in general practice, where most of these disorders are treated. Explore the associations between common psychological diagnoses and somatic symptom diagnoses in Norwegian urban general practice. A retrospective cohort study including electronic medical data from 15 750 patients aged 16-65 years from 35 GPs in six GP offices in Oslo, Norway, during 12 months in 2014-2015. We explored prevalences and associations between anxiety-, depression-, and stress-related diagnoses, and somatic symptom diagnoses. Patients with anxiety-, depression- and stress-related diagnoses had a mean number of 2.9±3.6 somatic symptom diagnoses during the 12 months, compared to 1.9±2.5 for patients without any psychological diagnoses (P < 0.001). The mean number of somatic symptoms was significantly higher for the different psychological diagnoses viewed separately, for both sexes and different age groups. There was an increase in probability for anxiety, depression, or stress-related diagnoses with an increasing number of somatic symptom diagnoses during the 12 months. We found a significant increase in somatic symptom diagnoses from ICPC-2 chapters: General and unspecified, digestive, cardiovascular, musculoskeletal, neurological, urological, female genital disorders and social problems. Associated symptom patterns were different for each of the included psychological diagnoses. This study shows that patients with anxiety, depression- and stress-related diagnoses present with increased and characteristic somatic symptoms compared to patients without these diagnoses in general practice.

Psychiatric and Physical Health Outcomes Associated with Interpersonal Violence: A Propensity Score Matching Approach.

This study examined the association between interpersonal violence and a range of psychiatric and physical health outcomes and assessed whether these associations changed when controlling for a stress-related diagnosis. An observational case-control study was conducted on a sample of 4,059 victims of violence. Using propensity score matching a number of risk factors (assessed five years prior assault) were used. Controls were matched 10:1 using the Danish Central Registry System. Outcomes were ICD-10 diagnoses of a range of psychiatric and physical health outcomes in the 15years post-injury. Statistically significant associations were found for all psychiatric conditions and a diagnosis of a drug or substance misuse disorder. These findings remained even after controlling for a diagnosis of a stress-related disorder. Large scale case-control studies using the Danish nationwide registers enables a powerful way of assessing the relative impact of exposure to interpersonal violence on the development of psychiatric and physical health problems.

Four-year survey of medically serious suicide attempters in Abu Dhabi.

It is well established that attempting suicide significantly increases a person's risk of completing suicide. The risk is considered to be particularly high in the first year after the attempt. Epidemiological information on suicide is scarce in the Middle East and the countries of the GCC region and there is a need to establish a reference point to measure future changes. We examined the epidemiology of suicide attempters requiring inpatient care in Abu Dhabi to identify associated factors that could aid local suicide prevention strategies. This 4-year (2011-2014) study of suicide attempters in the city of Abu Dhabi included all attempters assessed by the consultation-liaison team and admitted to the 3 main governmental general hospitals. We identified 364 suicide attempts with an annual incidence of 6 per 100 000 population. The mean age was 28.7 years. Females comprised 59.6% of the attempters and were more likely to be below age 30 years. Around 40% of the psychiatric diagnoses among attempters were related to stress and 17.9% to depression. Overdosing was the chosen method in 50.6% of the attempters, with 32.7% overdosing on paracetamol and females being more likely to use this method. Just over 13% of the attempters had made one previous attempt and 2.2% had made more than one. Females younger than 30 years were at higher risk of attempting suicide, with overdosing on paracetamol as the preferred method. Stress-related diagnoses were predominant in the attempters.

Unspecified stress disorders and risk of arterial and venous thromboembolic disease in the Danish population

BackgroundPosttraumatic stress disorder is a well-documented risk factor for cardiovascular disease. Whether non-specific stress-related psychopathology also increases risk is less well known. MethodsIn 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. ResultsIncidence 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. LimitationsUnspecified stress reaction has less precise criteria than other stress-related diagnoses, and we could not adjust for some potential confounders. ConclusionsOur 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.

Genetic Variants Associated With Anxiety and Stress-Related Disorders

Anxiety and stress-related disorders are among the most common mental disorders. Although family and twin studies indicate that both genetic and environmental factors play an important role underlying their etiology, the genetic underpinnings of anxiety and stress-related disorders are poorly understood. To estimate the single-nucleotide polymorphism-based heritability of anxiety and stress-related disorders; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to evaluate the association of psychiatric comorbidities with genetic findings. This genome-wide association study included individuals with various anxiety and stress-related diagnoses and controls derived from the population-based Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) study. Lifetime diagnoses of anxiety and stress-related disorders were obtained through the national Danish registers. Genes of interest were further evaluated in mice exposed to chronic social defeat. The study was conducted between June 2016 and November 2018. Diagnoses of a relatively broad diagnostic spectrum of anxiety and stress-related disorders. The study sample included 12 655 individuals with various anxiety and stress-related diagnoses and 19 225 controls. Overall, 17 740 study participants (55.6%) were women. A total of 7308 participants (22.9%) were born between 1981-1985, 8840 (27.7%) between 1986-1990, 8157 (25.6%) between 1991-1995, 5918 (18.6%) between 1996-2000, and 1657 (5.2%) between 2001-2005. Standard association analysis revealed variants in PDE4B to be associated with anxiety and stress-related disorder (rs7528604; P = 5.39 × 10-11; odds ratio = 0.89; 95% CI, 0.86-0.92). A framework of sensitivity analyses adjusting for mental comorbidity supported this result showing consistent association of PDE4B variants with anxiety and stress-related disorder across analytical scenarios. In mouse models, alterations in Pde4b expression were observed in those mice displaying anxiety-like behavior after exposure to chronic stress in the prefrontal cortex (P = .002; t = -3.33) and the hippocampus (P = .001; t = -3.72). We also found a single-nucleotide polymorphism heritability of 28% (standard error = 0.027) and that the genetic signature of anxiety and stress-related overlapped with psychiatric traits, educational outcomes, obesity-related phenotypes, smoking, and reproductive success. This study highlights anxiety and stress-related disorders as complex heritable phenotypes with intriguing genetic correlations not only with psychiatric traits, but also with educational outcomes and multiple obesity-related phenotypes. Furthermore, we highlight the candidate gene PDE4B as a robust risk locus pointing to the potential of PDE4B inhibitors in treatment of these disorders.

Comparison of exhaustion symptoms in patients with stress-related and other psychiatric and somatic diagnoses

BackgroundSeveral rating scales assessing stress-related symptoms of exhaustion have emerged in recent years. However, more knowledge is needed about the performance of these rating scales in patients with stress-related disorders as well as in other patient groups. With the recently developed Karolinska Exhaustion Disorder Scale (KEDS), we compared symptoms of exhaustion in different patient groups that were sorted according to diagnosis.MethodsPatients were sampled consecutively from departments of occupational medicine (DOM) at three Danish hospitals. The total study group comprised 698 care-seeking patients (487 women). Patients with stress-related diagnoses (n = 217; the International Classification of Diseases [ICD]-10 code F43: reaction to severe stress and adjustment disorder) were compared to a diverse group of patients with a range of somatic diagnoses (n = 338) and to patients with other psychiatric diagnoses (n = 143), including subgroups with major depression disorder (n = 34; F32 and F33) and problems related to employment and unemployment (n = 99; Z56). The data were analysed using linear mixed models with the SPSS statistical program.ResultsThe mean KEDS sum score in patients with stress-related diagnoses (29.3; SD = 8.0) was significantly higher than in patients with other psychiatric diagnoses (25.9; SD = 9.5) and in patients with somatic diagnoses (17.6; SD = 10.8). The subgroup with a major depression disorder had high mean KEDS sum scores (31.4, SD = 8.1), similar to patients with stress-related diagnoses, while the mean KEDS sum score in patients with problems related to employment and unemployment (Z56) was 23.5 (SD = 9.0). Young and old patients scored similarly on KEDS, but in patients with somatic diagnoses, female patients scored significantly higher than male patients.ConclusionThe symptoms of exhaustion measured with KEDS were higher in patients with stress-related diagnoses and major depression disorder than in patients with somatic diagnoses. The intermediate level of the symptoms of exhaustion that were associated with problems related to employment and unemployment, (Z56) compared to the lower level of the symptoms with somatic diagnoses, suggests that KEDS might be useful in detecting mild, prodromal states of exhaustion. This needs further investigation.

66 - GENOME-WIDE ASSOCIATION STUDY OF ANXIETY AND STRESS-RELATED DISORDERS

Background In Europe, over 70 million people are annually suffering from anxiety and stress-related disorders and over 90% of patients with these disorders have another comorbid mental or somatic disorder. Therefore, it is of strong interest to identify the risk factors of these disorders. Heritability estimates vary between 30% and 50%, however first Genome-Wide Association Studies (GWAS) have been limited by their small sample sizes. As anxiety and stress-related disorders are likely to configure various expressions of abnormalities in the basic stress-response system, we aimed to conduct a GWAS aggregating a large number of cases with varying diagnoses of anxiety and stress-related disorders. Methods The study is making use of a Danish nation-wide population-based sample collected by the Lundbeck Foundation Initiative for Integrative Psychiatric Research including 14,711 cases with anxiety and stress-related diagnoses and 17,857 controls. Data were processed using the Ricopili pipeline; imputation is based on the 1000 genomes phase 3 as reference panel. GWAS was conducted using the imputed marker dosages and an additive logistic regression model. Analyses were supplemented by comparing severe mental disorder with comorbid anxiety and stress-related disorder to those without, using a propensity-score-matched design. SNP heritability and genetic correlation with other traits were computed using LD-score regression. Results In case-control design several SNPs located in the PDE4B gene achieved genome-wide significance. The analyses comparing mental disorders with and without comorbid anxiety and stress-related disorders reveled no significant signal. The SNP heritability estimate for anxiety was 14%, 33% for stress-related disorders and 26% for the combined phenotype. We found a positive significant genetic correlation of anxiety and stress-related disorders with neuroticism, depression, bipolar disorder, schizophrenia and smoking; and a negative genetic correlation with college completion, years of schooling, age at menarche and age of first birth. Discussion This is the first GWAS meta-analysis on anxiety and stress-related disorders demonstrating influences of common genetic variation in the etiology of these disorders and indicating PDE4B as a susceptibility locus. Consistent with phenotypic observations, anxiety and stress-related disorders share genetic variants with psychiatric traits in the expected direction.