Comorbidity and sex differences in functional disorders and internalizing disorders.
Thomas, Nathaniel S, Gillespie, Nathan A, Kendler, Kenneth S et al. · General hospital psychiatry · 2024 · DOI
Quick Summary
This study looked at how often ME/CFS, fibromyalgia, and irritable bowel syndrome occur together with depression and anxiety in over 107,000 people. The researchers found that people with one of these conditions are much more likely to also have depression or anxiety than would be expected by chance. Interestingly, these connections were even stronger in men than in women.
Why It Matters
Understanding the high rates of comorbidity between ME/CFS and mood/anxiety disorders is crucial for improving clinical recognition and treatment strategies. This finding suggests that patients with ME/CFS should be routinely screened for depression and anxiety, and vice versa, which may lead to more comprehensive and effective care. The sex-based differences highlighted here also point toward potentially different biological or psychosocial mechanisms in men and women, informing future mechanistic research.
Observed Findings
Functional disorders and internalizing disorders show high comorbidity with odds ratios ranging from 3.2 to 12.6.
Comorbidity associations were significantly stronger in men than in women.
Participants with three or more concurrent diagnoses (e.g., ME/CFS + FM + depression) occurred more frequently than statistically expected by chance.
The study included 107,849 participants with mean age 49.3 years, 58.6% women.
Inferred Conclusions
Functional disorders and internalizing disorders share common etiological mechanisms or pathways that produce higher-than-chance comorbidity patterns.
Sex differences in comorbidity patterns suggest biological or psychosocial factors may operate differently in men versus women.
Clinical assessment of these conditions should incorporate screening for co-occurring diagnoses, as multiple simultaneous diagnoses appear to cluster beyond random probability.
Remaining Questions
What are the causal and temporal relationships between functional disorders and internalizing disorders—does one precede the other, or do they share a common biological pathway?
Why are comorbidity associations stronger in men, and what biological or psychosocial mechanisms explain this sex difference?
What This Study Does Not Prove
This study cannot establish whether depression and anxiety cause ME/CFS, result from it, or share a common underlying cause—only that they frequently co-occur. The cross-sectional design means we cannot determine the temporal sequence of symptom onset. Additionally, the results are based on self-reported diagnoses using criteria rather than clinical evaluation, which may affect accuracy and generalizability beyond the Dutch population studied.
Tags
Symptom:PainFatigue
Method Flag:PEM Not DefinedExploratory OnlyMixed CohortSex-Stratified
Are there distinct biological subtypes of these conditions characterized by different comorbidity patterns, and how might this inform personalized treatment approaches?
Whether these findings replicate across diverse populations outside the Netherlands and in clinical samples versus population-based cohorts.