Prospective associations between major depressive disorder, generalized anxiety disorder, fibromyalgia, and [ME/CFS], 2025, Thomas et al

[forestglip]

Prospective associations between major depressive disorder, generalized anxiety disorder, fibromyalgia, and myalgic encephalomyelitis/chronic fatigue syndrome

Nathaniel Stembridge Thomas, Michael C. Neale, Kenneth S. Kendler, Hanna M. van Loo, Nathan A. Gillespie

Background
Functional disorders (FDs) are associated with internalizing disorders (IDs). Studies investigating the nature of these associations over time are limited. We tested the direction of causation between measures of IDs (major depressive disorder [MDD], generalized anxiety disorder [GAD]) and FDs (fibromyalgia [FM] and myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS]) measured across two waves of longitudinal data (N = 108,034 and N = 73,590).

Methods
The Lifelines Cohort Study is a large prospective population-based cohort study in the northeast of the Netherlands. We tested competing causal models for the longitudinal association between IDs and FDs and, to follow-up results from the model with all IDs and FDs, tested the direction of causation between MDD and FM.

Results
FDs were more stable over time than IDs. Initial model comparisons support a bidirectional relationship between most IDs and FDs. Follow-up analyses support a unidirectional model where FM predicts MDD over time (β = 0.14, 95% confidence interval = [0.11, 0.18]), but not vice versa.

Conclusions
The cross-time associations between ME/CFS, MDD, and GAD appear bidirectional (causal in both directions). Our results are consistent with, but not demonstrative of, a causal relationship from FM to MDD. The consequences of specific FDs vary, underscoring the value of studying these conditions as distinct constructs.

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[Utsikt]

The diagnostic criteria for current ME/CFS were assessed using the 1994 Centers for Disease Control and Prevention (CDC) criteria (Fukuda et al., Reference Fukuda, Straus, Hickie, Sharpe, Dobbins and Komaroff1994). To meet the CDC diagnostic criteria, participants had to indicate (1) that they had experienced chronic fatigue for 6 or more months, and (2) that the fatigue significantly interfered with daily activities and work in the past 6 months. In addition, (3) the participant had to report concurrently four or more of the eight mentioned additional symptoms in the past 6 months. Each of these three criteria was used as binary items for factor analysis.

That sounds like a very broad set of criteria that would give a lot of false positives.

Yup, table 1 has the prevalence at 6.9 % for wave 2 and 8.8 % for wave 3.

 

[Utsikt]

And wouldn’t you expect a relationship to both of the FDs if your theory is that they are basically caused by the same factors?

Doesn’t this point towards chronic fatigue (that’s all we can say based on the criteria) and chronic pain being caused by two different mechanisms?

Isn’t this a huge blow to their FD models, assuming their methods are valid?