Factors associated with new onset of depression and anxiety symptoms differ by sex in the COPDGene study

Kirsten Voorhies; Jess G Fiedorowicz; Abebaw M Yohannes; Gregory L Kinney; Dawn L DeMeo; Elizabeth A Regan; James D Crapo; Edwin K Silverman; Christoph Lange; Karin F Hoth; Sharon M Lutz

doi:10.1016/j.jpsychores.2025.112345

Factors associated with new onset of depression and anxiety symptoms differ by sex in the COPDGene study

J Psychosom Res. 2025 Oct:197:112345. doi: 10.1016/j.jpsychores.2025.112345. Epub 2025 Aug 7.

Authors

Affiliations

¹ Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, MA, USA.
² The Ottawa Hospital, Ottawa Hospital Research Institute, and University of Ottawa, Ottawa, Ontario, Canada.
³ Department of Physical Therapy, University of Alabama at Birmingham, Birmingham, AL, USA; Division of Pulmonary, Allergy and Critical Care, University of Alabama at Birmingham, Birmingham, AL, USA.
⁴ Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁵ Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Department of Medicine, National Jewish Health, Denver, CO, USA.
⁷ Department of Biostatistics, T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
⁸ Department of Psychiatry and Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA.
⁹ Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, MA, USA; Department of Biostatistics, T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. Electronic address: smlutz@hsph.harvard.edu.

PMID: 40840304
DOI: 10.1016/j.jpsychores.2025.112345

Abstract

Objective: Examine clinical and demographic variables associated with new onset depression and anxiety symptoms and assess moderation by sex in COPDGene, a cohort study of current and former smokers at risk for or with chronic obstructive pulmonary disease (COPD).

Methods: In the COPDGene study, 2653 adults had the hospital anxiety (HADS-A) and depression (HADS-D) scales available at phase 2 and 3, as well as clinical and demographic variables available at 2 and non-elevated HADS at phase 2. We defined new onset depression symptoms as HADS-D elevated at phase 3 (HADS-D ≥ 8) versus no new onset as HADS-D not elevated at either phase (HADS-D < 8). New onset anxiety symptoms were defined identically using HADS-A. We used logistic regression models among all participants and stratified by sex and assessed sex interactions for variables associated with the outcome for only one sex.

Results: Among males, COPD Assessment test (CAT) score was positively associated with new onset depression (β = 0.08, p = 1.9 × 10^-5) and anxiety (β = 0.06, p = 1.4 × 10^-3) symptoms. Among females, the modified Medical Research Council (mMRC) dyspnea was positively associated with new onset anxiety symptoms (β = 0.33, p = 1.4 × 10^-3). We found sex by CAT score (β = -0.06, p = 0.02) and sex by mMRC dyspnea (β = 0.42, p = 5.1 × 10^-3) interactions on new onset anxiety symptoms, and sex by CAT score interaction (β = -0.05, p = 0.04) on new onset depression symptoms.

Conclusions: These findings highlight the importance of understanding factors that increase risk for depression and anxiety among smokers at risk for or with COPD and are moderated by sex.

Keywords: Anxiety; Depression; Hospital anxiety and depression scale (HADS); Sex.

MeSH terms

Aged
Anxiety* / epidemiology
Cohort Studies
Depression* / epidemiology
Female
Humans
Male
Middle Aged
Pulmonary Disease, Chronic Obstructive* / epidemiology
Pulmonary Disease, Chronic Obstructive* / psychology
Risk Factors
Sex Factors
Smoking* / epidemiology