Clinical heterogeneity in major depressive disorder underlies comorbidity with functional disorders

Major depressive disorder (MDD) is clinically heterogeneous. MDD is also often comorbid with functional disorders (FDs) such as fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and irritable bowel syndrome (IBS), but previous studies have not assessed whether individuals with particular MDD subtypes are more likely to experience FDs. We analyzed data from 10,563 lifetime MDD cases (mean age=50.5 (SD=11.9), 71.8% female) from the Lifelines Cohort Study. Lifetime MDD symptoms from DSM-5 criterion A were assessed in 2018. Current FDs were assessed according to diagnostic criteria between 2014-2017. First, we modeled the effect of 12 disaggregated MDD symptoms on FM, ME/CFS, and IBS diagnoses. Next, we used Latent Class Analysis to classify MDD cases based on their symptoms to determine if specific symptom profiles underlie the comorbidity between MDD and FDs. Most, but not all, MDD symptoms were associated with FD diagnoses, suggesting that some features of MDD are particularly important to the comorbidity between MDD and FDs. We found that a five-class solution provided the best fit to the data. Two classes, termed severe typical and anhedonia/weight gain, reported increased prevalence of all FDs. The effect of severe typical class probability on FM and ME/CFS was mediated by a common liability, while the effect of anhedonia/weight gain was, at least in part, specific to each condition. The comorbidity between MDD and FDs does not appear to result from a single mechanism. Identification of the mechanisms that underlie the association between MDD and FDs is a priority for future work.