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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.

SUBMITTER: Lamers F

PROVIDER: S-EPMC5545705 | biostudies-other | 2016 Jul

REPOSITORIES: biostudies-other

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Serum proteomic profiles of depressive subtypes.

Lamers F F Bot M M Jansen R R Chan M K MK Cooper J D JD Bahn S S Penninx B W J H BW

Translational psychiatry 20160712 7

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 wi ...[more]

PMID: 27404283

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Project description:BACKGROUND:Major depressive disorder and bipolar disorder are prevalent and debilitating psychiatric disorders that are difficult to distinguish, as their diagnosis is based on behavioural observations and subjective symptoms. Quantitative protein profile analysis might help to objectively distinguish between these disorders and increase our understanding of their pathophysiology. Thus, this study was conducted to compare the peripheral protein profiles between the two disorders. METHODS:Serum samples were collected from 18 subjects with major depressive disorder and 15 subjects with bipolar disorder. After depleting abundant proteins, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and label-free quantification were performed. Data-dependent acquisition data were statistically analysed from the samples of 15 subjects with major depressive disorder and 10 subjects with bipolar disorder who were psychotropic drug-free. Two-sided t-tests were performed for pairwise comparisons of proteomes to detect differentially-expressed proteins (DEPs). Ingenuity Pathway Analysis of canonical pathways, disease and functions, and protein networks based on these DEPs was further conducted. RESULTS:Fourteen DEPs were significant between subjects with major depressive disorder and those with bipolar disorder. Ras-related protein Rab-7a (t = 5.975, p = 4.3 × 10- 6) and Rho-associated protein kinase 2 (t = 4.782, p = 8.0 × 10- 5) were significantly overexpressed in subjects with major depressive disorder and Exportin-7 (t = -4.520, p = 1.5 × 10- 4) was significantly overexpressed in subjects with bipolar disorder after considering multiple comparisons. Bioinformatics analysis showed that cellular functions and inflammation/immune pathways were significantly different. CONCLUSIONS:Ras-related protein Rab-7a, Rho-associated protein kinase 2, and Exportin-7 were identified as potential peripheral protein candidates to distinguish major depressive disorder and bipolar disorder. Further large sample studies with longitudinal designs and validation processes are warranted.

Project description:BackgroundThe culture and expansion of human cells for clinical use requires the presence of human serum or plasma in culture media. Although these supplements have been extensively characterized in their chemical composition, only recently it has been possible to provide by high throughput protein analysis, a comprehensive profile of the soluble factors contributing to cell survival. This study analyzed and compared the presence of 100 proteins including chemokines, cytokines and soluble factors in six different types of media supplements: serum, plasma, recalcified plasma, heat inactivated serum, heat inactivated plasma and heat inactivated recalcified plasma.MethodsSerum, plasma, recalcified plasma, and heat inactivated supplements were prepared from ten healthy subjects. The levels of 100 soluble factors were measured in each sample using a multiplexed ELISA assay and compared by Eisen hierarchical clustering analysis.ResultsA comparison of serum and plasma levels of soluble factors found that 2 were greater in plasma but 18 factors were greater in serum including 11 chemokines. The levels of only four factors differed between recalcified plasma and plasma. Heat inactivation had the greatest effect on soluble factors. Supervised Eisen hierarchical clustering indicated that the differences between heat inactivated supplements and those that were not were greater than the differences within these two groups. The levels of 36 factors differed between heat inactivated plasma and plasma. Thirty one of these factors had a lower concentration in heat inactivated plasma including 12 chemokines, 4 growth factors, 4 matrix metalloproteases, and 3 adhesion molecules. Heat inactivated decalcified plasma is often used in place of heat inactivated serum and the levels of 19 soluble factors differed between these two supplements.ConclusionOur report provides a comprehensive protein profile of serum, plasma recalcified plasma, and heat inactivated supplements. This profile represents a qualitative and quantitative database that can aid in the selection of the appropriate blood derived supplement for human cell cultures with special requirements.

Dataset Information

Serum proteomic profiles of depressive subtypes.

Publications

Serum proteomic profiles of depressive subtypes.

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