Risk of Major Depressive Disorder Spikes Following a Medical Diagnosis, Endures for Decades: New Data

The risk of major depressive disorder (MDD) is significantly elevated following the onset of a range of medical conditions, according to a large Danish cohort study published in The Lancet Public Health. Led by a team from Copenhagen University Hospital, researchers analyzed more than 100 million person-years of data and found that individuals recently diagnosed with any of 9 categories of physical illnesses face more than double the risk of developing MDD compared to their healthy peers.1

The risk appears to peak within the first month after diagnosis and the uptick is further elevated among those aged 60 years or older, patients who are hospitalized, and individuals with multiple comorbidities.

Specifically investigators found that after onset of any medical condition, the risk of developing MDD was more than 2 times greater (hazard ratio [HR] 2.26; 95% CI 2.25–2.28) among affected individuals compared to those without a medical condition. Within the first month of onset, the MDD risk doubled to more than 4 times greater (HR, 4.62, 95% CI 4.50–4.74). During that first month following onset, the highest rates of MDD were recorded in:

• Hospitalized patients (HR 11.83, 11.25–12.45),
• Adults aged 60 years and older (HR 9.04, 8.63–9.47)
• Individuals with at least 2 comorbid conditions (HR 8.92, 8.74–9.11)

Even 20 years after onset of a condition, the absolute risk for MDD was 18.9% in men and 24.4% in women compared with 6.9% in matched men without a medical condition and 10.7% in matched women.1

Global Impact of MDD Rising

The global burden of major depressive disorder continues to climb, with current WHO projections suggesting it will top the ranks of disabling conditions by 2030.2 WHO currently ranks MDD as the third greatest contributor to "life-years lost due to ill health, disability, or early death."2 Corresponding author Per E Sigvardsen, PhD, and colleagues state that while previous research has established the frequent overlap of depression and medical conditions, most studies have been limited by confounding baseline illness and lacked clear indication of temporal sequence. Even as the debate over screening for depression in adults persists, left untreated, comorbid depression is known to worsen outcomes in chronic disease management, the authors wrote.1

This study aimed to clarify whether MDD risk increases immediately or is delayed after the diagnosis of a chronic medical condition, and whether certain subgroups are more susceptible than others.1

Study Design and Methods

Sigvardsen et al utilized Denmark’s comprehensive nationwide health registries to retrospectively follow 6,528,353 residents between January 1, 1995, and December 31, 2022. Exclusion criteria included any diagnosis of depression or a medical condition during a 5-year washout period before entering the cohort. The study examined onset of MDD across 9 medical categories: circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, hematological, cancers, and neurologic conditions.

For purposes of the study, MDD was defined by ICD-10 codes or repeated prescription of antidepressants. Adjusted Cox regression models accounted for key covariates, with subgroup analyses by age, number of comorbidities, clinical setting of diagnosis, and sex.1

Additional Findings

• Musculoskeletal conditions had the strongest association with MDD (HR 2.50), and endocrine conditions had the weakest association (HR 1.35).
• Haematologic conditions showed the highest risk in the first month after diagnosis.
• Pulmonary conditions showed the lowest risk in the first month after diagnosis.

For other categories (neurological, cancers, gastrointestinal, urogenital, circulatory), the exact HRs were not reported in the summary materials, but all categories showed an elevated risk compared to individuals without a medical condition.1

Among the study's limitations the authors acknowledged the observational design and the restriction that poses on generalizing findings to populations outside Denmark. They also noted that MDD case numbers may have been inflated given that antidepressant prescriptions were used to identify depression cases and the medications may have been used for other indications. On the other hand, mild cases managed without medication likely went undetected. Lack of data on illness severity and duration of hospitalization further tempers interpretation.1

Authors' Observations. This large-scale, register-based analysis affirms a heightened—especially immediate— and enduring risk of major depressive disorder following the onset of chronic medical conditions. The authors underscored the substantial public health implications linked to their results. "Policy makers should prioritise better integration of mental health services into primary and specialist medical care settings, which could facilitate early detection and treatment of major depressive disorder." Physicians across specialties should remain highly attuned to early MDD symptoms in newly diagnosed patients, with an emphasis on the elderly, hospitalized, and those managing multiple conditions, they added. Integrating mental health screenings and support into primary and specialty care stands to improve outcomes for this vulnerable population.1

References

1. Sigvardsen PE, Fosbøl E, Jørgensen A, Torp-Pedersen C, Køber L, Kofoed KF. Medical conditions and the risk of subsequent major depressive disorder: a nationwide, register-based, retrospective cohort study. Lancet Public Health. 2025;10:e503–11. doi:10.1016/ S2468-2667(25)00073-8

2. Chan VKY, Leung MYM, Chan SSM, et al. Projecting the 10-year costs of care and mortality burden of depression until 2032: a Markov modelling study developed from real-world data. Lancet Reg Health West Pac. 2024;45:101026. doi: 10.1016/j.lanwpc.2024.101026