Network Motif Detection in the Network of Inflammatory Markers and Depression Symptoms among Patients with Stable Coronary Heart Disease: Insights from the Heart and Soul Study

Background. Network motif analysis is a technique used to explore recurrent and statistically significant subgraphs within a network. Applying a motif analysis to the complex network of inflammation and depression may yield nuanced insight into the specific interaction mechanisms between inflammatory markers and individual depression symptoms, which is our aim. Methods. This cross-sectional study is based on patients with stable coronary heart disease (CHD). A partial correlation network was initially constructed to link inflammatory markers, including C-reactive protein (CRP), Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), individual depression symptoms, and covariates. A network-centric approach searched all possible non-isomorphic subgraph patterns of size k = 4 in the network. Results. Although CRP, IL-6, and TNF-α displayed an insignificant association with specific depression symptoms, the motif analysis revealed various subgraph patterns of interactions between depression symptoms associated with MCP-1. Generally, MCP-1 formed a closed loop with psychomotor problems and sleep disturbances, and this configuration was connected in various forms with other symptoms, particularly cognitive (e.g., feelings of worthlessness, concentration difficulty, and suicidal ideation) and neurovegetative/somatic (e.g., appetite changes and fatigue) symptoms. Moreover, MCP-1 was frequently associated with a closed-loop triangle comprising cognitive and neurovegetative/somatic symptoms but not with mood symptoms (e.g., loss of interest and feelings of sadness). Conclusions. The findings provide insight into how MCP-1 may be involved in the pathology of depression among patients with stable CHD in a more precise manner. This study also proposes future directions for research on depression.