Femke Lamers1, Yuri Milaneschi2, Johannes H Smit2, Robert A Schoevers3, Gayle Wittenberg4, Brenda W J H Penninx2. 1. Department of Psychiatry, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Electronic address: f.lamers@vumc.nl. 2. Department of Psychiatry, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. 3. Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 4. Janssen Research & Development, Titusville, New Jersey.
Abstract
BACKGROUND: While cross-sectional associations of inflammatory markers interleukin-6 (IL-6) and C-reactive protein with major depressive disorder are well established, evidence for longitudinal associations mostly comes from studies on depression symptoms, not diagnoses. This study examined cross-sectional and bidirectional longitudinal associations between depression diagnosis and symptoms in an adult sample over a 6-year period. METHODS: Data were obtained from the baseline (n = 2416) and 2- and 6-year follow-up assessments (n = 1925 and n = 1924, respectively) of the Netherlands Study of Depression and Anxiety. C-reactive protein and IL-6 were assessed at each wave, as were the Composite International Diagnostic Interview and Inventory of Depressive Symptomatology. Linear mixed models and generalized estimating equation models with a binomial distribution were used to study longitudinal associations between depression and inflammation and vice versa. RESULTS: There was a consistent cross-sectional association between current depressive disorder (vs. no current disorder) and symptoms with IL-6 across all follow-up measurements (Cohen's ddepression diagnosis = 0.06, p = .017; Bstandardized Inventory of Depressive Symptomatology = 0.029, SE = 0.011, p = .008). In longitudinal analyses, higher IL-6 levels predicted subsequent chronic course in those with a diagnosis at baseline in women but not in men (odds ratiowomen = 1.13, 95% confidence interval = 1.04-1.23), and both depressive disorder and high severity predicted higher IL-6 levels at the subsequent follow-up (p values < .01). In contrast, C-reactive protein was not associated with current depression in cross-sectional and longitudinal analyses. CONCLUSIONS: In this longitudinal study, cross-sectional and bidirectional longitudinal associations were found between depression and IL-6 levels. This underlines the importance of targeting inflammation pathways in the treatment of major depressive disorder. IL-6 could be a potential marker for patient profiling in personalized medicine approaches.
BACKGROUND: While cross-sectional associations of inflammatory markers interleukin-6 (IL-6) and C-reactive protein with major depressive disorder are well established, evidence for longitudinal associations mostly comes from studies on depression symptoms, not diagnoses. This study examined cross-sectional and bidirectional longitudinal associations between depression diagnosis and symptoms in an adult sample over a 6-year period. METHODS: Data were obtained from the baseline (n = 2416) and 2- and 6-year follow-up assessments (n = 1925 and n = 1924, respectively) of the Netherlands Study of Depression and Anxiety. C-reactive protein and IL-6 were assessed at each wave, as were the Composite International Diagnostic Interview and Inventory of Depressive Symptomatology. Linear mixed models and generalized estimating equation models with a binomial distribution were used to study longitudinal associations between depression and inflammation and vice versa. RESULTS: There was a consistent cross-sectional association between current depressive disorder (vs. no current disorder) and symptoms with IL-6 across all follow-up measurements (Cohen's ddepression diagnosis = 0.06, p = .017; Bstandardized Inventory of Depressive Symptomatology = 0.029, SE = 0.011, p = .008). In longitudinal analyses, higher IL-6 levels predicted subsequent chronic course in those with a diagnosis at baseline in women but not in men (odds ratiowomen = 1.13, 95% confidence interval = 1.04-1.23), and both depressive disorder and high severity predicted higher IL-6 levels at the subsequent follow-up (p values < .01). In contrast, C-reactive protein was not associated with current depression in cross-sectional and longitudinal analyses. CONCLUSIONS: In this longitudinal study, cross-sectional and bidirectional longitudinal associations were found between depression and IL-6 levels. This underlines the importance of targeting inflammation pathways in the treatment of major depressive disorder. IL-6 could be a potential marker for patient profiling in personalized medicine approaches.
Authors: Erika J Wolf; Mark W Logue; Xiang Zhao; Nikolaos P Daskalakis; Filomene G Morrison; Shaline Escarfulleri; Annjanette Stone; Steven A Schichman; Regina E McGlinchey; William P Milberg; Cidi Chen; Carmela R Abraham; Mark W Miller Journal: Psychoneuroendocrinology Date: 2020-04-13 Impact factor: 4.905
Authors: Julia J Schubert; Mattia Veronese; Tim D Fryer; Roido Manavaki; Manfred G Kitzbichler; Maria A Nettis; Valeria Mondelli; Carmine M Pariante; Edward T Bullmore; Federico E Turkheimer Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2021-01-28