Depression and immunity in adolescents: early precursors to disease?

© 2012 Dr. Michelle Lynn ByrneInflammation and immune dysfunction have been proposed to be mechanisms relevant to clinical depression. However, research on this topic is limited by the paucity of lifespan and longitudinal studies, making it difficult to address causality. This project aimed to examine inflammatory and depressive measures in adolescents from the community using both cross-sectional and prospective longitudinal designs. Experiment 1 was a cross-sectional, two-group study of 13 clinically depressed adolescents aged 13-18 years (11 females), and 13 age- and sex-matched healthy controls, both recruited from the community. Sixteen cytokines were measured in saliva and serum. Depressed adolescents displayed significantly elevated levels of C-reactive protein (CRP), Haptoglobin, Serum Amyloid P (SAP), and Alpha-2-macroglobulin (A2M) in saliva compared to controls, but not in serum, or for any other cytokine. Depressed adolescents also did not display a higher ratio of T helper cell 1- to T helper cell 2-type cytokines compared to controls. Experiment 2 was a prospective study of 67 adolescents (27 females) followed from 12-18 years of age and recruited from the community. Self-report depressive symptoms measured by the Center for Epidemiological Studies Depression Scale (CES-D) and Axis-I psychopathology measured by The Schedule for Affective Disorder and Schizophrenia for School-age Children (KSADS) were measured at four phases, and four salivary acute-phase proteins (CRP, Haptoglobin, SAP, and A2M) were measured at Phase II. Temperamental negative emotionality (NEM) was also assessed at age 12. Results showed that elevated CRP was significantly correlated with elevated CES-D scores cross-sectionally, but no inflammatory markers predicted the onset of a depressive illness or an increase in depressive symptoms over time. There was a significant Sex x CRP interaction effect on CES-D measured at Phase I, II, and IV, with a relationship between CRP and CES-D only apparent for females. Examining only females demonstrated significant associations between CRP and CES-D at all four phases, including CES-D measured two years prior to inflammation, suggesting that for females, depressive symptoms may precede elevated levels of CRP, however, further longitudinal research is required that measures inflammation at more than one time point. At Phase II, there were significant interactions of NEM temperament x CRP on CES-D, with a relationship between CRP and CES-D only for those with a high NEM score. Post-hoc analyses showed that body mass index (BMI) was also a significant moderator of the relationship between CRP and CES-D at Phase II, with a stronger association for participants with a higher BMI score. Measures of early-life stress and childhood trauma were not associated with inflammatory markers. These results suggest that salivary CRP is a marker of adolescent depression, but levels of this inflammatory marker do not predict the development of depressive illness. The results, along with other research, suggest that depressive symptoms may be a risk factor for chronic inflammation and associated medical diseases, especially for females. Furthermore, obesity may be another consequence of depression which can lead to this observed elevated inflammation. Finally, sex hormones should be considered in models of depression, obesity, and inflammation