Detecting Associations between Major Depressive Disorder Treatment and Essential Hypertension using Electronic Health Records.
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ABSTRACT:
SUBMITTER: Pathak J
PROVIDER: S-EPMC4419773 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
Detecting Associations between Major Depressive Disorder Treatment and Essential Hypertension using Electronic Health Records.
Pathak Jyotishman J Simon Gyorgy G Li Dingcheng D Biernacka Joanna M JM Jenkins Gregory J GJ Chute Christopher G CG Hall-Flavin Daniel K DK Weinshilboum Richard M RM
AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science 20140407
In this observational study, we investigate the correlation between depression and hypertension on a cohort of patients treated for major depressive disorder using Selective Serotonin Reuptake Inhibitors (SSRIs) and assess the effect of depression treatment on the diagnoses and treatment for essential hypertension. Our results indicate that the positive effect of successful depression treatment can be discovered and estimated from electronic health record (EHR) data even for a small sample size. ...[more]
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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.
2011-10-04 | E-GEOD-19738 | biostudies-arrayexpress
Project description:Many healthcare facilities enforce security on their electronic health records (EHRs) through a corrective mechanism: some staff nominally have almost unrestricted access to the records, but there is a strict ex post facto audit process for inappropriate accesses, i.e., accesses that violate the facility's security and privacy policies. This process is inefficient, as each suspicious access has to be reviewed by a security expert, and is purely retrospective, as it occurs after damage may have been incurred. This motivates automated approaches based on machine learning using historical data. Previous attempts at such a system have successfully applied supervised learning models to this end, such as SVMs and logistic regression. While providing benefits over manual auditing, these approaches ignore the identity of the users and patients involved in a record access. Therefore, they cannot exploit the fact that a patient whose record was previously involved in a violation has an increased risk of being involved in a future violation. Motivated by this, in this paper, we propose a collaborative filtering inspired approach to predicting inappropriate accesses. Our solution integrates both explicit and latent features for staff and patients, the latter acting as a personalized "finger-print" based on historical access patterns. The proposed method, when applied to real EHR access data from two tertiary hospitals and a file-access dataset from Amazon, shows not only significantly improved performance compared to existing methods, but also provides insights as to what indicates an inappropriate access.
| S-EPMC3967851 | biostudies-other
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.
2011-10-05 | GSE19738 | GEO
Project description:Major depressive disorder (MDD) exhibits numerous clinical, epidemiological, and molecular features that are consistent with partially inherited and partially acquired epigenetic misregulation. We performed microarray based DNA modification study of MDD, utilizing affected and unaffected samples from white blood cells from monozygotic twins discordant for MDD, post-mortem prefrontal cortex tissues, and sperm samples. We performed DNA methylome analysis on white blood cells from monozygotic twins discordant for depression (n=200), pre-frontal cortex (n=71), and germline samples (n=33) from affected individuals and controls (total n=304). DNA samples were enriched for unmodified fraction of the genome using DNA-modification sensitive restriction enzyme digestion followed by adaptor-mediated PCR. The enriched fractions were labelled with a fluorescent dye (Cy5) and hybridized onto the array with a common reference pool (Cy3) generated from individuals unrelated to this study.
2012-04-27 | E-GEOD-37579 | biostudies-arrayexpress
Project description:The purpose of this case-control genetic association study was to explore potential relationships between polymorphisms in the limbic system-associated membrane protein (LSAMP) gene and mood and anxiety disorders. A total of 21 single-nucleotide polymorphisms (SNPs) from the LSAMP gene were analyzed in 591 unrelated patients with the diagnoses of major depressive disorder (MDD) or panic disorder (PD) and in 384 healthy control subjects. The results showed a strong association between LSAMP SNPs and MDD, and a suggestive association between LSAMP SNPs and PD. This is the first evidence of a possible role of LSAMP gene in mood and anxiety disorders in humans.
| S-EPMC3432189 | biostudies-literature
Project description:Identify blood proteins relevant to paroxetine response in patients with major depressive disorder (MDD)
2022-05-20 | PXD028947 | Pride
Project description:BACKGROUND:Electronic mental (e-mental) health care for depression aims to overcome barriers to and limitations of face-to-face treatment. Owing to the high and growing demand for mental health care, a large number of such information and communication technology systems have been developed in recent years. Consequently, a diverse system landscape formed. OBJECTIVE:This literature review aims to give an overview of this landscape of e-mental health systems for the prevention and treatment of major depressive disorder, focusing on three main research questions: (1) What types of systems exist? (2) How technologically advanced are these systems? (3) How has the system landscape evolved between 2000 and 2017? METHODS:Publications eligible for inclusion described e-mental health software for the prevention or treatment of major depressive disorder. Additionally, the software had to have been evaluated with end users and developed since 2000. After screening, 270 records remained for inclusion. We constructed a taxonomy concerning software systems, their functions, how technologized these were in their realization, and how systems were evaluated, and then, we extracted this information from the included records. We define here as functions any component of the system that delivers either treatment or adherence support to the user. For this coding process, an elaborate classification hierarchy for functions was developed yielding a total of 133 systems with 2163 functions. The systems and their functions were analyzed quantitatively, with a focus on technological realization. RESULTS:There are various types of systems. However, most are delivered on the World Wide Web (76%), and most implement cognitive behavioral therapy techniques (85%). In terms of content, systems contain twice as many treatment functions as adherence support functions, on average. Furthermore, autonomous systems, those not including human guidance, are equally as technologized and have one-third less functions than guided ones. Therefore, lack of guidance is neither compensated with additional functions nor compensated by technologizing functions to a greater degree. Although several high-tech solutions could be found, the average system falls between a purely informational system and one that allows for data entry but without automatically processing these data. Moreover, no clear increase in the technological capabilities of systems showed in the field, between 2000 and 2017, despite a marked growth in system quantity. Finally, more sophisticated systems were evaluated less often in comparative trials than less sophisticated ones (OR 0.59). CONCLUSIONS:The findings indicate that when developers create systems, there is a greater focus on implementing therapeutic treatment than adherence support. Although the field is very active, as evidenced by the growing number of systems developed per year, the technological possibilities explored are limited. In addition to allowing developers to compare their system with others, we anticipate that this review will help researchers identify opportunities in the field.
| S-EPMC6997926 | biostudies-literature
Project description:Resistant hypertension is defined as high blood pressure that remains above treatment goals in spite of the concurrent use of three antihypertensive agents from different classes. Despite the important health consequences of resistant hypertension, few studies of resistant hypertension have been conducted. To perform a genome-wide association study for resistant hypertension, we defined and identified cases of resistant hypertension and hypertensives with treated, controlled hypertension among >47,500 adults residing in the US linked to electronic health records (EHRs) and genotyped as part of the electronic MEdical Records & GEnomics (eMERGE) Network. Electronic selection logic using billing codes, laboratory values, text queries, and medication records was used to identify resistant hypertension cases and controls at each site, and a total of 3,006 cases of resistant hypertension and 876 controlled hypertensives were identified among eMERGE Phase I and II sites. After imputation and quality control, a total of 2,530,150 SNPs were tested for an association among 2,830 multi-ethnic cases of resistant hypertension and 876 controlled hypertensives. No test of association was genome-wide significant in the full dataset or in the dataset limited to European American cases (n = 1,719) and controls (n = 708). The most significant finding was CLNK rs13144136 at p = 1.00x10-6 (odds ratio = 0.68; 95% CI = 0.58-0.80) in the full dataset with similar results in the European American only dataset. We also examined whether SNPs known to influence blood pressure or hypertension also influenced resistant hypertension. None was significant after correction for multiple testing. These data highlight both the difficulties and the potential utility of EHR-linked genomic data to study clinically-relevant traits such as resistant hypertension.
| S-EPMC5319785 | biostudies-literature
Project description:We examined the genetic profile of postmortem brain (hippocampal) samples; 15 brains from patients diagnosed with MDD were matched to brains from healthy subjects based on gender, race and age. Gene expression profiles in the dentate gyrus and CA1 subregions of the hippocampus were assessed by cDNA hybridization to 48K human HEEBO whole genome microarrays (Microarray, Inc). Two-group comparison: MDD (13 male, 8 female) vs. Control (11 male, 7 female). Dentate Gyrus (DG): 15 pairs of samples (1 array per pair); CA1: 15 pairs of samples (1 array per pair). Biological replicates. We can not provide a list of normalized values for each individual hybridization (per chip), but rather have a list of average expression values for all hybridizations used in the experiment (n=15). See supplementary files below. CODES: AAm, African American; C, Caucasian; CO, carbon monoxide; CVD, cardiovascular disease; ETOH, ethanol; F, female; Hx, history of alcohol abuse but not currently active; M, male; MDD, Major Depressive disorder, ND, no psychotropic medication detected; NOS, not otherwise specified, OD, drug overdose; PE, prior episode of major depression with psychotic features; PMI, postmortem interval (hours); SIGSW, self-inflicted gunshot wound; [1], Psychotrophic prescriptions within last month; [2], MDD in remission; [3], prescriptions for six days prior to death; *, samples present only in array sets for the dentate gyrus; **, samples present only in array sets for CA1.
2010-10-17 | E-GEOD-24095 | biostudies-arrayexpress
Project description:BackgroundIdentifying implausible clinical observations (e.g., laboratory test and vital sign values) in Electronic Health Record (EHR) data using rule-based procedures is challenging. Anomaly/outlier detection methods can be applied as an alternative algorithmic approach to flagging such implausible values in EHRs.MethodsThe primary objectives of this research were to develop and test an unsupervised clustering-based anomaly/outlier detection approach for detecting implausible observations in EHR data as an alternative algorithmic solution to the existing procedures. Our approach is built upon two underlying hypotheses that, (i) when there are large number of observations, implausible records should be sparse, and therefore (ii) if these data are clustered properly, clusters with sparse populations should represent implausible observations. To test these hypotheses, we applied an unsupervised clustering algorithm to EHR observation data on 50 laboratory tests from Partners HealthCare. We tested different specifications of the clustering approach and computed confusion matrix indices against a set of silver-standard plausibility thresholds. We compared the results from the proposed approach with conventional anomaly detection (CAD) approaches, including standard deviation and Mahalanobis distance.ResultsWe found that the clustering approach produced results with exceptional specificity and high sensitivity. Compared with the conventional anomaly detection approaches, our proposed clustering approach resulted in significantly smaller number of false positive cases.ConclusionOur contributions include (i) a clustering approach for identifying implausible EHR observations, (ii) evidence that implausible observations are sparse in EHR laboratory test results, (iii) a parallel implementation of the clustering approach on i2b2 star schema, and (3) a set of silver-standard plausibility thresholds for 50 laboratory tests that can be used in other studies for validation. The proposed algorithmic solution can augment human decisions to improve data quality. Therefore, a workflow is needed to complement the algorithm's job and initiate necessary actions that need to be taken in order to improve the quality of data.
| S-EPMC6652024 | biostudies-literature