title: Serum proteomic profiles of depressive subtypes.
abstract: Depression is a highly heterogeneous disorder. Accumulating evidence suggests biological and genetic differences between subtypes of depression that are homogeneous in symptom presentation. We aimed to evaluate differences in serum protein profiles between persons with atypical and melancholic depressive subtypes, and compare these profiles with serum protein levels of healthy controls. We used the baseline data from the Netherlands Study of Depression and Anxiety on 414 controls, 231 persons with a melancholic depressive subtype and 128 persons with an atypical depressive subtype for whom the proteomic data were available. Depressive subtypes were previously established using a data-driven analysis, and 171 serum proteins were measured on a multi-analyte profiling platform. Linear regression models were adjusted for several covariates and corrected for multiple testing using false discovery rate q-values. We observed differences in analytes between the atypical and melancholic subtypes (9 analytes, q<0.05) and between atypical depression and controls (23 analytes, q<0.05). Eight of the nine markers differing between the atypical and melancholic subtype overlapped with markers from the comparison between atypical subtype and controls (mesothelin, leptin, IGFBP1, IGFBP2, FABPa, insulin, C3 and B2M), and were mainly involved in cellular communication and signal transduction, and immune response. No markers differed significantly between the melancholic subtype and controls. To conclude, although some uncertainties exist in our results as a result of missing data imputation and lack of proteomic replication samples, many of the identified analytes are inflammatory or metabolic markers, which supports the notion of atypical depression as a syndrome characterized by metabolic disturbances and inflammation, and underline the importance and relevance of subtypes of depression in biological and genetic research, and potentially in the treatment of depression.
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Lamers
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Bot
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: R
authors.identifier: 0000-0002-3333-6737
authors.initials: R
authors.lastname: Jansen
authors.affiliation: Department of Chemical Engineering and Biotechnology, Institute of Biotechnology, University of Cambridge, Cambridge, UK.
authors.forename: M K
authors.initials: MK
authors.lastname: Chan
authors.affiliation: Department of Chemical Engineering and Biotechnology, Institute of Biotechnology, University of Cambridge, Cambridge, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Cooper
authors.affiliation: Department of Chemical Engineering and Biotechnology, Institute of Biotechnology, University of Cambridge, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: Bahn
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: B W J H
authors.initials: BW
authors.lastname: Penninx
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003176:Complement C3 / Q000378:metabolism; D003866:Depressive Disorder / Q000097:blood* / Q000145:classification / Q000523:psychology; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D020738:Leptin / Q000097:blood; D016014:Linear Models; D008297:Male; D000090204:Mesothelin; D008875:Middle Aged; D009426:Netherlands; D040901:Proteomics; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D003176:Complement C3; D050556:Fatty Acid-Binding Proteins; D058851:GPI-Linked Proteins; C032231:IGFBP1 protein, human; C577903:IGFBP2 protein, human; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D020738:Leptin; D001613:beta 2-Microglobulin; D000090204:Mesothelin