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Higher Serum C Reactive Protein Determined C Reactive Protein Single-Nucleotide Polymorphisms Are Involved in Inherited Depression.

ABSTRACT: Objective:The pathogenesis of depression is not fully understood yet, but studies have suggested higher circulating C reactive protein (CRP) level might relate to depression occurrence. However, due to high variability of patients' individual condition, the results to date are inconsistent. Considering CRP single-nucleotide polymorphisms (SNPs) could also regulate plasma CRP levels, in the present study, we hypothesized that inherited CRP allelic variations may co-vary with depressive symptomatology. Methods:We recruited 60 depression patients with family depression history and 60 healthy control volunteers into this project. We detected circulation CRP level as well as genome CRP SNPs from participants of this project. Results:We have found a significantly higher circulating CRP level in patients with a positive family history. Furthermore, we also identified some certain inherited CRP SNPs (A allele in rs1417938 and C allele in rs1205) could up regulate serum CRP level and distributed more in depression patients with family history. Conclusion:Our finding may raise new evidence that genetically increased serum CRP level through SNPs variation is likely to induce family inherited depression.

SUBMITTER: Wang S

PROVIDER: S-EPMC6111223 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Higher Serum C Reactive Protein Determined C Reactive Protein Single-Nucleotide Polymorphisms Are Involved in Inherited Depression.

Wang Shiliang S Zhong Hua H Lu Meijuan M Song Guohua G Zhang Xiaomei X Lin Min M Yang Shengliang S Qian Mincai M

Psychiatry investigation 20180727 8

<h4>Objective</h4>The pathogenesis of depression is not fully understood yet, but studies have suggested higher circulating C reactive protein (CRP) level might relate to depression occurrence. However, due to high variability of patients' individual condition, the results to date are inconsistent. Considering CRP single-nucleotide polymorphisms (SNPs) could also regulate plasma CRP levels, in the present study, we hypothesized that inherited CRP allelic variations may co-vary with depressive sy ...[more]

PMID: 30048584

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Project description:BackgroundPeriventricular extracellular oedema, myelin damage, inflammation, and glial reactions are common neuropathological events that occur in the brain in congenital hydrocephalus. The periventricular white matter is the most affected region. The present study aimed to identify altered molecular and cellular biomarkers in the neocortex that can function as potential therapeutic targets to both treat and evaluate recovery from these neurodegenerative conditions. The hyh mouse model of hereditary hydrocephalus was used for this purpose.MethodsThe hyh mouse model of hereditary hydrocephalus (hydrocephalus with hop gait) and control littermates without hydrocephalus were used in the present work. In tissue sections, the ionic content was investigated using energy dispersive X-ray spectroscopy scanning electron microscopy (EDS-SEM). For the lipid analysis, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) was performed in frozen sections. The expression of proteins in the cerebral white matter was analysed by mass spectrometry. The oligodendrocyte progenitor cells (OPCs) were studied with immunofluorescence in cerebral sections and whole-mount preparations of the ventricle walls.ResultsHigh sodium and chloride concentrations were found indicating oedema conditions in both the periventricular white matter and extending towards the grey matter. Lipid analysis revealed lower levels of two phosphatidylinositol molecular species in the grey matter, indicating that neural functions were altered in the hydrocephalic mice. In addition, the expression of proteins in the cerebral white matter revealed evident deregulation of the processes of oligodendrocyte differentiation and myelination. Because of the changes in oligodendrocyte differentiation in the white matter, OPCs were also studied. In hydrocephalic mice, OPCs were found to be reactive, overexpressing the NG2 antigen but not giving rise to an increase in mature oligodendrocytes. The higher levels of the NG2 antigen, diacylglycerophosphoserine and possibly transthyretin in the cerebrum of hydrocephalic hyh mice could indicate cell reactions that may have been triggered by inflammation, neurocytotoxic conditions, and ischaemia.ConclusionOur results identify possible biomarkers of hydrocephalus in the cerebral grey and white matter. In the white matter, OPCs could be reacting to acquire a neuroprotective role or as a delay in the oligodendrocyte maturation.

Project description:BACKGROUND:C-reactive protein (CRP) is a candidate biomarker for major depressive disorder (MDD), but it is unclear how peripheral CRP levels relate to the heterogeneous clinical phenotypes of the disorder.AimTo explore CRP in MDD and its phenotypic associations. METHOD:We recruited 102 treatment-resistant patients with MDD currently experiencing depression, 48 treatment-responsive patients with MDD not currently experiencing depression, 48 patients with depression who were not receiving medication and 54 healthy volunteers. High-sensitivity CRP in peripheral venous blood, body mass index (BMI) and questionnaire assessments of depression, anxiety and childhood trauma were measured. Group differences in CRP were estimated, and partial least squares (PLS) analysis explored the relationships between CRP and specific clinical phenotypes. RESULTS:Compared with healthy volunteers, BMI-corrected CRP was significantly elevated in the treatment-resistant group (P = 0.007; Cohen's d = 0.47); but not significantly so in the treatment-responsive (d = 0.29) and untreated (d = 0.18) groups. PLS yielded an optimal two-factor solution that accounted for 34.7% of variation in clinical measures and for 36.0% of variation in CRP. Clinical phenotypes most strongly associated with CRP and heavily weighted on the first PLS component were vegetative depressive symptoms, BMI, state anxiety and feeling unloved as a child or wishing for a different childhood. CONCLUSIONS:CRP was elevated in patients with MDD, and more so in treatment-resistant patients. Other phenotypes associated with elevated CRP included childhood adversity and specific depressive and anxious symptoms. We suggest that patients with MDD stratified for proinflammatory biomarkers, like CRP, have a distinctive clinical profile that might be responsive to second-line treatment with anti-inflammatory drugs.Declaration of interestS.R.C. consults for Cambridge Cognition and Shire; and his input in this project was funded by a Wellcome Trust Clinical Fellowship (110049/Z/15/Z). E.T.B. is employed half time by the University of Cambridge and half time by GlaxoSmithKline; he holds stock in GlaxoSmithKline. In the past 3 years, P.J.C. has served on an advisory board for Lundbeck. N.A.H. consults for GlaxoSmithKline. P.d.B., D.N.C.J. and W.C.D. are employees of Janssen Research & Development, LLC., of Johnson & Johnson, and hold stock in Johnson & Johnson. The other authors report no financial disclosures or potential conflicts of interest.

Dataset Information

Higher Serum C Reactive Protein Determined C Reactive Protein Single-Nucleotide Polymorphisms Are Involved in Inherited Depression.

Publications

Higher Serum C Reactive Protein Determined C Reactive Protein Single-Nucleotide Polymorphisms Are Involved in Inherited Depression.

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