The PrimeCog study aims to describe the symptomatology and pathophysiology of stress-induced exhaustion disorder (SED) and major depressive disorder (MDD) compared to healthy controls (HC). The participants will be recruited at primary care centers, and samples of blood, saliva, and hair will be collected. Digital questionnaires covering psychosocial variables and screening instruments for the detection of depression, anxiety, etc., along with a digital cognitive test battery, will be performed at home. Subsequently, an MRI of the brain will be performed, and analysis of biomarkers for stress, inflammation, and neurodegeneration will be conducted. These procedures will be repeated after twelve and twenty-four months. The study will investigate differences in the biomarkers, neuroimaging findings, and cognitive abilities between patients with SED, MDD, and controls over time. Associations between the symptom severity of MDD/SED and psychosocial variables, cognition, MRI, and the biomarkers will also be examined. The aim is to provide new diagnostic tools for differentiation between MDD and SED and guide individualized treatment based on underlying pathophysiology and cognitive function. All necessary competences for conducting this extensive study are represented within the research group. The PrimeCog study is unique in its comprehensive design, addressing knowledge gaps, and directly comparing these diagnoses over time in primary care, where patients are typically treated.

Research problems and specific questions Major depressive disorder (MDD) and stress induced exhaustion disorder (SED) are two growing public health concerns in primary care, causing individual suffering and affecting work productivity. MDD and SED call for different treatment strategies, but diagnosis differentiation pose several difficulties. Both conditions are linked to stress-related factors at work, and prescribed sick leave is a common treatment strategy. The main reasons for sick leave in DEP and UMS is cognitive difficulties, but no objective measures of cognition is used today. The aim of the PrimeCog project is to provide new diagnostic tools for differentiation between MDD and SED and guide individualized treatment based on cognitive function and underlying pathophysiology.

Data and method The project is a multicenter longitudinal, prospective research project on patients with newly diagnosed MDD or SED and healthy controls, n=100/group. The participants will be recruited at primary care centers. Data is collected through a digital cognitive test battery carried out at home, a questionnaire with screening scales and psychosocial risk factors, biomarkers in blood, saliva and hair, and a magnetic resonance imaging (MRI) of the brain. These procedures will be repeated after 12 and 24 months.

Societal relevance and utilization New diagnostic tools are needed for DEP and UMS in primary care to improve differential diagnosis and to individualize treatment in order to get the right intervention and treatment as quickly as possible. This could hypothetically contribute to shorter illness duration and reduce the length of sick leave. By investigating digital cognitive testing in primary care patients with MDD or SED, the PrimeCog project seeks to enhance diagnosis and follow-up which may prevent negative outcomes for individuals and benefit society by advancing mental health care as a whole. Digital cognitive testing is a new tool in primary care, and potentially both time- and cost-effective approach for objectively measuring cognitive symptoms.

Inclusion Criteria:

1. adults 18 to 65 years old;
2. fluent in Swedish;
3. corrected to normal vision and hearing;
4. (for cases), newly diagnosed with MDD or SED (i.e., received as new diagnosis at the visit to the physician) according to the diagnostic criteria from DSM-V (MDD) and the Swedish Board of Health and Welfare (SED)

Exclusion Criteria:

1. already ongoing treatment for MDD/SED or previous diagnosis of MDD/SED within the last year;
2. history of serious mental illness (defined as mental illness that has required psychiatric in-patient care);
3. acute cerebrovascular event or severe head trauma in the last 6 months;
4. known cognitive impairment;
5. substance dependence, ongoing or past;
6. motor disability or impairment affecting interaction with the digital tests;
7. photosensitive epilepsy or -migraines.

For the MRI subgroup, any contraindication to MRI is an exclusion criterion.

Patients and controls in primary care.

Probably upon request from mandated researchers, but yet to be decided.