Fig 1.
A brief overview of the study methods is shown here, from sample collection to data analysis. Abbreviations: NESDA (Netherlands Study of Depression and Anxiety); MDD (major depressive disorder); CMA (comorbid MDD and anxiety disorder(s)).
Fig 2.
Sample exclusion for NESDA patient groups and controls after data pre-processing.
Numbers are indicated in brackets. Red boxes = initial data after pre-processing; blue boxes = excluded data; green boxes = data after exclusion. Participants were excluded if they were not fasting or if they had a current/lifetime anxiety disorder or dysthymia only, current minor depression, a depressive and/or anxiety diagnosis within two years of the baseline measurement, or a lifetime bipolar disorder diagnosed at the two-year assessment. Abbreviations: NESDA (Netherlands Study of Depression and Anxiety); MDD (major depressive disorder); CMA (comorbid MDD and anxiety disorder(s)).
Fig 3.
Analytes with significant interactions between log2-transformed serum concentration and sex in MDD compared to controls.
The natural logarithm of the odds ratio (OR; the ratio of the odds of MDD diagnosis associated with a two-fold increase in the untransformed serum concentration of that analyte from the logistic model) is shown for males and females with 95% confidence intervals. P- and q-values (FDR-adjusted p-values) are shown for the interaction tests. Abbreviations: OR (odds ratio); Q (q-value, FDR-adjusted p—value); TFF3 (trefoil factor 3); IGFBP (insulin-like growth factor binding protein); B2M (β2-microglobulin); uPAR (urokinase-type plasminogen activator receptor); FABP (fatty acid-binding protein); TBG (thyroxine-binding globulin); HGF (hepatocyte growth factor); vWF (von Willebrand factor); PPP (pancreatic polypeptide); TN-C (tenascin-C); CRP (C-reactive protein); CD5L (CD5 antigen-like); OPG (osteoprotegerin); TNFR2 (tumor necrosis factor receptor 2); VCAM (vascular cell adhesion molecule); FAS (FASLG receptor); MDC (macrophage derived chemokine); PARC (pulmonary and activation-regulated chemokine); MMP (matrix metalloproteinase); MIP-3B (macrophage inflammatory protein-3β); IL-2RA (interleukin-2 receptor α). † Eotaxin-1 was no longer significant when analyzed using multiple imputation (see S4 Table).
Fig 4.
Analytes with overlapping significant interactions between sex and log2-transformed serum concentration in MDD and (A) CMA and (B) remitted MDD compared to controls.
The natural logarithm of the odds ratio (OR; ratio of the odds of diagnosis associated with a two-fold increase in the untransformed serum concentration of that analyte from the logistic model) is shown for males and females with 95% confidence intervals. P- and q-values (FDR-adjusted p-values) are shown for the interaction tests. Analytes are plotted in the same order as Fig 3. Abbreviations: CMA (comorbid MDD and anxiety disorder(s)); OR (odds ratio); Q (q-value, FDR-adjusted p—value); TFF3 (trefoil factor 3); IGFBP (insulin-like growth factor binding protein); B2M (β2-microglobulin); FAS (FASLG receptor); MIP-3B (macrophage inflammatory protein-3β).
Fig 5.
ROC curve illustrating classification of MDD patients from controls for males and females using repeated ten-fold cross validation of logistic regression with BIC forward stepwise selection of all analytes.
The legend shows AUCs and median p-values of tests on repeated cross validations in brackets. Markers selected in forward stepwise selection of log2-transformed analyte data are shown in the right panel. Abbreviations: AUC (area under the ROC curve); P (median p-value); MDD (major depressive disorder); CD5L (CD5 antigen-like); IGFBP (insulin-like growth factor binding protein); TFF3 (trefoil factor 3); HGF (hepatocyte growth factor); EGF (epidermal growth factor).