ArticleBMC psychiatry2026
Disentangling comorbidity: symptom dimensions of internalizing and functional disorders in a large general population sample.
Article in BMC psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundInternalizing disorders (IDs) and functional disorders (FDs) are highly comorbid, however the mechanisms underlying their co-occurrence remain unclear. This study investigated the symptom dimensions of major depressive disorder (MDD), generalized anxiety disorder (GAD), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS) symptoms in the general population to understand comorbidity at the symptom level.
methodWe analyzed cross-sectional data from 108,418 adult participants in the Dutch Lifelines Cohort Study, including 30 symptoms from ID and FD diagnostic criteria. The sample was randomly split into two subsets (n = 54,209 each), with exploratory factor analysis conducted in the training set and confirmatory factor analysis in the testing set. Associations between the identified symptom dimensions and known risk factors (e.g., demographics, lifestyle, stress) for IDs and FDs, as well as their alignment with ID and FD diagnoses based on diagnostic criteria, were examined.
resultsFive symptom dimensions best captured the structure of ID and FD symptoms: depression, anxiety, IBS, musculoskeletal pain, and general malaise. Symptoms of ME/CFS and FM did not form separate symptom dimensions but loaded on two distinct dimensions: musculoskeletal pain and general malaise. The general malaise dimension mostly captured the transdiagnostic symptoms that were part of almost all ID/FD diagnoses, such as concentration difficulty, fatigue and unrefreshing sleep, plus a few symptoms from the ME/CFS criteria. This general malaise dimension was correlated with every other dimension (excluding the IBS dimension) and associated with all five disorders. Chronic stress was the one risk factor associated with all dimensions.
conclusionsThe diagnostic symptoms of IDs and FDs load on four disorder-specific dimensions and one dimension with transdiagnostic symptoms, general malaise. The general malaise dimension may be central to disorder comorbidity and a key target for further research. CLINICAL TRIAL NUMBER : Not applicable.
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