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ASMT gene expression correlates with cognitive impairment in patients with recurrent depressive disorder.

ABSTRACT: BACKGROUND: Recurrent depressive disorder is a multifactorial disease; one of the typical features is cognitive impairment. The purpose of this study was analysis of ASMT gene expression both on mRNA and protein levels in patients with recurrent depressive disorder (rDD) and assessment of the relationship between plasma level of ASMT protein, gene expression on mRNA level, and cognitive performance. MATERIAL AND METHODS: The study included 236 subjects: patients with rDD (n=131) and healthy subjects (n=105, CG). Cognitive function assessment was based on: Trail Making Test, The Stroop Test, Verbal Fluency Test (VFT), and Auditory Verbal Learning Test (AVLT). RESULTS: Both mRNA and protein expression levels of ASMT gene were significantly higher in healthy subjects when compared to rDD. The average ASMT mRNA expression level measured for the entire group was M=0.21 (SD=0.09), and the protein level was M=12.84 (SD=3.29). In patients with rDD, statistically significant correlations occurred between both mRNA and protein expression levels and part A of the TMT (negative correlation) and verbal fluency test (positive correlation). In the group CG, there was no statistically significant association between the analyzed variables. In the entire group there was a statistically significant correlation between both ASMT mRNA and protein expression levels and all the neuropsychological tests used in the survey. CONCLUSIONS: 1. Our study confirms previous results showing decreased mRNA and protein expression levels of ASMT gene in depression. 2. Our data suggest a relationship between decreased mRNA and protein expression levels of ASMT gene and cognitive impairment.

SUBMITTER: Talarowska M

PROVIDER: S-EPMC4052942 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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ASMT gene expression correlates with cognitive impairment in patients with recurrent depressive disorder.

Talarowska Monika M Szemraj Janusz J Zajączkowska Marlena M Gałecki Piotr P

Medical science monitor : international medical journal of experimental and clinical research 20140602

<h4>Background</h4>Recurrent depressive disorder is a multifactorial disease; one of the typical features is cognitive impairment. The purpose of this study was analysis of ASMT gene expression both on mRNA and protein levels in patients with recurrent depressive disorder (rDD) and assessment of the relationship between plasma level of ASMT protein, gene expression on mRNA level, and cognitive performance.<h4>Material and methods</h4>The study included 236 subjects: patients with rDD (n=131) and ...[more]

PMID: 24881886

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Project description:ObjectivesDepressive symptoms and cognitive impairment often concur in older persons. Differentiating the cause of cognitive impairment in older persons with Depressive Disorder (DD) from other diseases such as Alzheimer's Disease (AD) is challenging. The goal of this study was to characterize cognitive impairment in older persons with DD.DesignCross-sectional retrospective observational clinical cohort study using patient records from 2014 to 2018.SettingGerontopsychiatric services of Ulm University at Bezirkskrankenhaus Günzburg serving as primary psychiatric care institution and tertiary referral center for psychiatric care for older persons.PartcipantsDD was diagnosed according to ICD-10 criteria. When indicated by the medical history or neuropsychological assessment further diagnostic procedures were initiated. Cerebrospinal fluid (CSF) tap was routinely the first additional procedure. If patients did not consent to CSF tap or contraindications were present, 18F-fluordesoxyglucose-PET (FDG-PET) or Amyloid-PET (Am-PET) were performed.Materials and methodsExtensive neuropsychological test battery to assess cognitive profile.Results457 subjects were diagnosed with DD (DD-all; age 50-94; 159 males, 298 females). Biomarkers were assessed in 176 persons; in 90 of these subjects AD-biomarkers were negative (DD-BM-; age 54-89; 40 males, 50 females), and in 86 subjects at least one biomarker was compatible with AD (DD-BM+; age 60-90; 31 males, 55 females). Cognitive performance was below healthy controls (HC; n = 56; age 50-80; 30 males, 26 females) for all groups of patients with DD. With case-control matching of HC and DD-BM- we find that executive functions are impaired in about one out of three and delayed recall in about two out of three patients with DD.ConclusionCognitive impairment is frequent in older persons with DD. Cognitive profile in older patients with DD without and with biomarkers of AD is not distinguishable. Therefore, cognitive impairment due to DD should be diagnosed after exclusion of comorbid AD.

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

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ASMT gene expression correlates with cognitive impairment in patients with recurrent depressive disorder.

Publications

ASMT gene expression correlates with cognitive impairment in patients with recurrent depressive disorder.

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