Inflammatory Phenotype of Depression Symptom Structure: A Network Perspective

There has been increasing interest in classifying inflammatory phenotypes of depression. Most investigations into inflammatory phenotypes solely have tested whether increased inflammation is associated with increased depression. This study expanded the definition of phenotype to include the structure of depression as a function of inflammation. Network models of depression symptoms were estimated in a sample of 4,537 adults 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) and non-elevated CRP as well as moderated network models with CRP moderating the associations between depression symptoms. Differences emerged at three levels of analysis (global, symptom-specific, symptom—symptom associations). Specifically, the elevated CRP group had greater global connectivity. Further, difficulty concentrating had higher expected influence (concordance with other symptoms) in the elevated CRP group. Finally, 14 out of 38 symptom—symptom associations were moderated by CRP. This study provides consistent evidence that the structure of depression symptoms varies as a function of CRP levels.