Using network analysis to examine links between individual depressive symptoms, inflammatory markers, and covariates

Abstract

Background Studies investigating the link between depressive symptoms and inflammation have yielded inconsistent results, which may be due to two factors. First, studies differed regarding the specific inflammatory markers studied and covariates accounted for. Second, specific depressive symptoms may be differentially related to inflammation. We address both challenges using network psychometrics. Methods We estimated seven regularized Mixed Graphical Models in the Netherlands Study of Depression and Anxiety (NESDA) data (N = 2321) to explore shared variances among (1) depression severity, modeled via depression sum-score, nine DSM-5 symptoms, or 28 individual depressive symptoms; (2) inflammatory markers C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α); (3) before and after adjusting for sex, age, body mass index (BMI), exercise, smoking, alcohol, and chronic diseases. Results The depression sum-score was related to both IL-6 and CRP before, and only to IL-6 after covariate adjustment. When modeling the DSM-5 symptoms and CRP in a conceptual replication of Jokela et al., CRP was associated with ‘sleep problems’, ‘energy level’, and ‘weight/appetite changes’; only the first two links survived covariate adjustment. In a conservative model with all 38 variables, symptoms and markers were unrelated. Following recent psychometric work, we re-estimated the full model without regularization: the depressive symptoms ‘insomnia’, ‘hypersomnia’, and ‘aches and pain’ showed unique positive relations to all inflammatory markers. Conclusions We found evidence for differential relations between markers, depressive symptoms, and covariates. Associations between symptoms and markers were attenuated after covariate adjustment; BMI and sex consistently showed strong relations with inflammatory markers.

Inflammatory phenotype of depression symptom structure: A network perspective

“…We found that several structural characteristics (i.e., global strength, expected influence, and symptom-symptom associations) of depression networks are moderated by CRP. This extends previous work that found that CRP is not equally associated with all symptoms of depression (e.g., Fried et al, 2019;Haroon et al, 2016;Jokela et al, 2016;Moriarity et al, 2020a), to demonstrate that differences in CRP might be associated with differences in depression symptom structure. Two of the three group-differences hypotheses were supported, with mixed support for the third.…”

“…This has led to calls for the inflammatory phenotyping of depression (Felger et al, 2018) and increased modeling of specific symptoms and symptom subtypes in immunopsychiatry . These pursuits have included profiling symptoms associated with inflammation (Fried et al, 2019;Jokela et al, 2016;Kappelmann et al, 2020;Moriarity et al, 2020a) as well as inflammatory proteins and cell counts associated with MDD (Lynall et al, 2020). Although there are many different inflammatory proteins, CRP, an acute phase reactant, arguably is the most widely studied.…”

The complex neurobiology of resilient functioning after childhood maltreatment

“…For example, we recently utilised network analysis to examine the complex interrelations of resilience factors and their relations with mental health symptoms in adolescents reporting childhood adversity [178], addressing the complexity of resilience. Resilient functioning results from complex interactions between multiple bodily systems [179] and network analyses make it possible to examine interactions between different symptoms and neurobiology at an unprecedented level of detail [180]. In sum, recent statistical innovations have the potential to approach questions of resilience using frameworks that fully embrace the complexity inherent in resilience research.…”

Psychotherapy or medication for depression? Using individual symptom meta-analyses to derive a Symptom-Oriented Therapy (SOrT) metric for a personalised psychiatry

“…Similarly, there are reports that lowgrade inflammation shows specificity for somatic symptoms of depression (e.g. sleep problems, low energy, or increased appetite) [101][102][103][104], so ongoing studies evaluating immunotherapy as a treatment for depression may benefit from symptom-based treatment allocation rules. We therefore encourage researchers to apply the SOrT metric to other treatment comparisons to evaluate its value as a precision medicine tool.…”