Inflammatory markers as predictors of depression and anxiety in adolescents: Statistical model building with component-wise gradient boosting

Background: Immune system abnormalities have been repeatedly observed in several psychiatric disorders, including severe depression and anxiety. However, whether specific immune mediators play an early role in the etiopathogenesis of these disorders remains unknown. Methods: In a longitudinal design, component-wise gradient boosting was used to build models of depression, assessed by the Mood-Feelings Questionnaire-Child (MFQC), and anxiety, assessed by the Screen for Child Anxiety Related Emotional Disorders (SCARED) in 254 adolescents from a large set of candidate predictors, including sex, race, 39 inflammatory proteins, and the interactions between those proteins and time. Each model was reduced via backward elimination to maximize parsimony and generalizability. Results: Component-wise gradient boosting and model reduction found that female sex, growth- regulated oncogene (GRO), and transforming growth factor alpha (TGF-alpha) predicted depression, while female sex predicted anxiety. Limitations: Differential onset of puberty as well as a lack of control for menstrual cycle may also have been responsible for differences between males and females in the present study. In addition, investigation of all possible nonlinear relationships between the predictors and the outcomes was beyond the computational capacity and scope of the present research. Conclusions: This study highlights the need for novel statistical modeling to identify reliable biological predictors of aberrant psychological behavior.