Connecting the dots: Network structures of internalizing and functional symptoms in a population-based cohort

Objective: Comorbidities between internalizing disorders (IDs) and functional disorders (FDs) are welldocumented, indicating shared pathways. However, their symptom-level relationships have been largely unexplored. This exploratory study employs a network approach to investigate symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS) to identify bridge symptoms explaining comorbidity between the two domains. Methods: We used cross-sectional data on 72,919 adult subjects from the Lifelines Cohort Study, a Dutch general population sample. A total of 38 symptoms representing diagnostic criteria of IDs and FDs were assessed with validated questionnaires. Network models were estimated using eLasso, based on the Ising model, to identify bridge symptoms. The Network Comparison Test (NCT) was used to test whether there were differences in network structure and strength across sex and age. Results: Symptoms were moderately connected, with a network density of 52.7%. ID and FD symptoms clustered in their respective domains, but were connected through the bridge symptoms, fatigue, difficulty concentrating, trouble sleeping, and unrefreshing sleep. Fatigue and difficulty concentrating had the most connections, associated with 86.6% and 78.9% of the other symptoms, respectively. NCTs indicated no differences in network connectivity between females versus males or younger versus older adults (>50 years). Conclusions: ID and FD symptoms are moderately interconnected. Bridge symptoms displaying strong connections to multiple disorders may play a central role in the mechanisms underpinning the comorbidity between IDs and FDs.