Neurobiological Effects of Work-related Adjustment Disorder (NeuroWAD)

INTRODUCTION: Stress is one of the greatest burdens of our society and often imply impairments in cognitive and emotional functions. The investigators hypothesize that changes in the brain's dopamine(DA)-based mesocorticolimbic projections in patients with work-related stress (adjustment disorder) will manifest in altered glucose metabolism in relation to neural activity and altered DA radiotracer binding potential at neurotransmitter and receptor level.

MATERIAL AND METHODS: Subjects and healthy controls undergo neuropsychiatric tests and PET/MR imaging with three tracers: [18F]FDG to measure glucose metabolism as a marker of neural activity, [11C]raclopride to investigate the DA binding potential in the striatum, and [11C]FLB 457 to study possible impaired mesocortical dopaminergic transmission. To demonstrate difference in glucose metabolism ≥2x41 patients/controls are needed.

OUTCOME: The investigators expect to find that symptoms of cognitive and motivational/reward deficits could be attributable to changes in frontal lobe and striatal glucose metabolism in >50% of patients and that changes in striatal D2 receptors and impaired mesocortical dopaminergic transmission in the prefrontal cortex are contributing factors.

CONCLUSION: This project aims to generate entirely new and objective evidence of stress-induced cerebral illness and provide a basis for in depth research and more rational management of this strenuous disorder.

Study Overview

• Status: Enrolling by invitation
• Conditions: Adjustment Disorder With Work Inhibition
• Intervention / Treatment: Radiation: PET/MR scans

Detailed Description

Recruitment procedure: The department of Occupational and Environmental Medicine (DOE) at OUH have developed a screening procedure to recruit patients diagnosed according to the ICD10 F43.2x, and exposed to predominant psychosocial work stressors. The patients are recruited among women and men aged 18-64. At the DOE subjects undergo a clinical diagnostic interview based on the ICD 10 criteria including screening for stressors in the psychosocial work environment and their relationship to disease development, private life strains, personal back-ground, mental vulnerability, and competing somatic disease, as well as tests for depression and anxiety symptoms, respectively the Beck Anxiety Inventory (BAI) and Major Depression Inventory (MDI). The psychosocial work environ-ment stressors being screened for are: quantitative demands, emotional demands, role conflict, role ambiguity, sup-port and encouragement, organizational justice, adequate education and training (skill level). The experience of stressors is assessed in relation to the most dominant stress models, "demand-control-support" (Karasek), "effort and reward imbalance at work" (Siegrist), "Stress as Offense two self" (Semmer), and classical stress theory focusing on appraisal / coping (Lazarus or Ursin).

The procedure is onward going to be performed automatically in an online environment. Due to the nature of neurobiology the scans must be conducted within a fairly short time period after the initial diagnosis. Hence a declaration of consent will be presented and signed at the day of the first scan, also ensuring that all additional questions can be answered by the main investigator. The scans will be conducted within a fortnight after the fists contact. In connection with the scans, the main investigator will conduct an SCAN-PSE interview for the assessment of mental symptoms to determine if the participant's condition has changed since they decided to participate in the trial. Healthy controls are recruited and matched with regard to gender, age, educational and occupational background. Further, controls are screened for confounding factors in a similar manner as the patient group.

• Study Type: Observational
• Enrollment (Anticipated): 82

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The patients are recruited among women aged 18-64 years.

Description

Inclusion Criteria:

Population and controls:

• Informed consent before study-related activity
• Aged 18 - 64
• Labour market suitability

Study population:

• Patients: F43.2
• Controls: Healthy individuals that meet the following inclusion and

Exclusion criteria.

Population, patients and controls:

• Comorbid diagnoses as for instance: cancer, cardiovascular disease, diabetes.
• Regular medication known to affect the central nervous system.
• Prior exposure to violence and other serious harassment in the workplace
• Psychosocial challenge in private life according to the screening criteria in the protocol.
• Other serious illness
• Metal in body
• Claustrophobia
• Pregnancy
• Confounding drug consumption
• Dependence e.g. alcohol, narcotics or other
• Persons within a period of 1 year have participated in scientific studies that use isotopes, or who have had greater diagnostic tests that utilize ionizing radiation.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Controls; Healthy controls	Radiation: PET/MR scans; Observations of glucose metabolism and dopamine binding potential
Stress patients; Patients diagnosed with work-related Adjustment disorder	Radiation: PET/MR scans; Observations of glucose metabolism and dopamine binding potential

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose metabolism	PET/MR scan	3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dopamine binding potential	PET/MR scan	3-4 years

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: Rigshospitalet, Denmark; University of Southern Denmark
• Investigators: Principal Investigator: Saga Steinmann Madsen, Engineering, OUH

Publications and helpful links

General Publications

• Madsen SS, Gjedde A, Brandt L, Pihl-Thingvad J, Videbech P, Gerke O, Hojlund-Carlsen PF. Neurobiological effects of work-related stress: protocol for a case-control neuroimaging study. Dan Med J. 2018 Nov;65(11):A5513.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2018
• Primary Completion (ANTICIPATED): March 1, 2023
• Study Completion (ANTICIPATED): March 1, 2023

Study Registration Dates

• First Submitted: October 13, 2017
• First Submitted That Met QC Criteria: November 6, 2017
• First Posted (ACTUAL): November 7, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 23, 2022
• Last Update Submitted That Met QC Criteria: September 22, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Occupational Stress; Neurobiology; Dopamine
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Adjustment Disorders
• Other Study ID Numbers: OP_483

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No