Inflammatory phenotype of depression symptom structure: A network perspective

Background: There has been increasing interest in classifying inflammatory phenotypes of depression. Most investigations into inflammatory phenotypes only have tested whether elevated inflammation is associated with elevated levels of depression symptoms, or risk for a diagnosis. This study expanded the definition of phenotype to include the structure of depression symptoms as a function of inflammation. Methods: Network models of depression symptoms were estimated in a sample of 4157 adults (mean age = 47.6, 51% female) from the 2015–2016 National Health and Nutrition Examination Survey (NHANES). Analyses included comparisons of networks between those with elevated (C-reactive protein (CRP) values ≥ 3.0 mg/L; N = 1696) and non-elevated CRP (N = 2841) as well as moderated network models with CRP group status and raw CRP values moderating the associations between depression symptoms. Results: Differences emerged at all levels of analysis (global, symptom-specific, symptom—symptom associations). Specifically, the elevated CRP group had greater symptom connectivity (stronger total associations between symptoms). Further, difficulty concentrating and psychomotor difficulties had higher expected influence (concordance with other symptoms) in the elevated CRP group. Finally, there was evidence that several symptom—symptom associations were moderated by CRP. Conclusions: This study provides consistent evidence that the structure of depression symptoms varies as a function of CRP levels. Greater symptom connectivity might contribute to why elevated CRP is associated with treatment-resistant depression. Additionally, differences in symptom structure might highlight different maintenance mechanisms and treatment targets for individuals with compared to those without elevated CRP. Finally, differences in symptom structure as a function of CRP highlight a potential misalignment of standard depression measures (the structure of which are evaluated on groups unselected for CRP levels) and the presentation of depression symptoms in those with elevated CRP.