scholarly journals A metabolome-wide association study in the general population reveals decreased levels of serum laurylcarnitine in people with depression

2021 ◽  
Author(s):  
Helena U. Zacharias ◽  
Johannes Hertel ◽  
Hamimatunnisa Johar ◽  
Maik Pietzner ◽  
Karoline Lukaschek ◽  
...  
Keyword(s):  
Suicidal Ideation ◽  
Multiple Testing ◽  
Depressive Disorders ◽  
Antidepressant Medication ◽  
Sensitivity Analyses ◽  
Acid Oxidation ◽  
Multiple Testing Correction ◽  
Metabolomics Data ◽  
Trend Study ◽  
Regression Tests

AbstractDepression constitutes a leading cause of disability worldwide. Despite extensive research on its interaction with psychobiological factors, associated pathways are far from being elucidated. Metabolomics, assessing the final products of complex biochemical reactions, has emerged as a valuable tool for exploring molecular pathways. We conducted a metabolome-wide association analysis to investigate the link between the serum metabolome and depressed mood (DM) in 1411 participants of the KORA (Cooperative Health Research in the Augsburg Region) F4 study (discovery cohort). Serum metabolomics data comprised 353 unique metabolites measured by Metabolon. We identified 72 (5.1%) KORA participants with DM. Linear regression tests were conducted modeling each metabolite value by DM status, adjusted for age, sex, body-mass index, antihypertensive, cardiovascular, antidiabetic, and thyroid gland hormone drugs, corticoids and antidepressants. Sensitivity analyses were performed in subcohorts stratified for sex, suicidal ideation, and use of antidepressants. We replicated our results in an independent sample of 968 participants of the SHIP-Trend (Study of Health in Pomerania) study including 52 (5.4%) individuals with DM (replication cohort). We found significantly lower laurylcarnitine levels in KORA F4 participants with DM after multiple testing correction according to Benjamini/Hochberg. This finding was replicated in the independent SHIP-Trend study. Laurylcarnitine remained significantly associated (p value < 0.05) with depression in samples stratified for sex, suicidal ideation, and antidepressant medication. Decreased blood laurylcarnitine levels in depressed individuals may point to impaired fatty acid oxidation and/or mitochondrial function in depressive disorders, possibly representing a novel therapeutic target.

scholarly journals Genetic biomarkers in the VEGF pathway predicting response to anti-VEGF therapy in age-related macular degeneration

2019 ◽  
Vol 4 (1) ◽  
pp. e000273
Author(s):  
Irina Balikova ◽  
Laurence Postelmans ◽  
Brigitte Pasteels ◽  
Pascale Coquelet ◽  
Janet Catherine ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Treatment Response ◽  
Multiple Testing ◽  
Age Related Macular Degeneration ◽  
Patient Specific ◽  
Multiple Testing Correction ◽  
Anti Vegf ◽  
Age Related ◽  
Vegf Pathway

ObjectiveAge-related macular degeneration (ARMD) is a leading cause of visual impairment. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard treatment for wet ARMD. There is however, variability in patient responses, suggesting patient-specific factors influencing drug efficacy. We tested whether single nucleotide polymorphisms (SNPs) in genes encoding VEGF pathway members contribute to therapy response.Methods and analysisA retrospective cohort of 281 European wet ARMD patients treated with anti-VEGF was genotyped for 138 tagging SNPs in the VEGF pathway. Per patient, we collected best corrected visual acuity at baseline, after three loading injections and at 12 months. We also registered the injection number and changes in retinal morphology after three loading injections (central foveal thickness (CFT), intraretinal cysts and serous neuroepithelium detachment). Changes in CFT after 3 months were our primary outcome measure. Association of SNPs to response was assessed by binomial logistic regression. Replication was attempted by associating visual acuity changes to genotypes in an independent Japanese cohort.ResultsAssociation with treatment response was detected for seven SNPs, including in FLT4 (rs55667289: OR=0.746, 95% CI 0.63 to 0.88, p=0.0005) and KDR (rs7691507: OR=1.056, 95% CI 1.02 to 1.10, p=0.005; and rs2305945: OR=0.963, 95% CI 0.93 to 1.00, p=0.0472). Only association with rs55667289 in FLT4 survived multiple testing correction. This SNP was unavailable for testing in the replication cohort. Of six SNPs tested for replication, one was significant although not after multiple testing correction.ConclusionIdentifying genetic variants that define treatment response can help to develop individualised therapeutic approaches for wet ARMD patients and may point towards new targets in non-responders.

scholarly journals Systematic review and meta-analysis of the prevalence of depressive symptoms, dysthymia and major depressive disorders among homeless people

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e040061
Author(s):  
Getinet Ayano ◽  
Asmare Belete ◽  
Bereket Duko ◽  
Light Tsegay ◽  
Berihun Assefa Dachew
Keyword(s):  
Systematic Review ◽  
Depressive Symptoms ◽  
Depressive Disorders ◽  
Meta Analysis ◽  
Random Effect ◽  
Homeless People ◽  
Sensitivity Analyses ◽  
Prevalence Rates ◽  
Major Depressive ◽  
Major Depressive Disorders

ObjectivesTo assess the global prevalence estimates of depressive symptoms, dysthymia and major depressive disorders (MDDs) among homeless people.DesignSystematic review and meta-analysis.Data sourcesDatabases including PubMed, Scopus and Web of Science were systematically searched up to February 2020 to identify relevant studies that have reported data on the prevalence of depressive symptoms, dysthymia and MDDs among homeless people.Eligibility criteriaOriginal epidemiological studies written in English that addressed the prevalence of depressive problems among homeless people.Data extraction and synthesisA random-effect meta-analysis was performed to pool the prevalence estimated from individual studies. Subgroup and sensitivity analyses were employed to compare the prevalence across the groups as well as to identify the source of heterogeneities. The Joanna Briggs Institute’s quality assessment checklist was used to measure the study quality. Cochran’s Q and the I2 test were used to assess heterogeneity between the studies.ResultsForty publications, including 17 215 participants, were included in the final analysis. This meta-analysis demonstrated considerably higher prevalence rates of depressive symptoms 46.72% (95% CI 37.77% to 55.90%), dysthymia 8.25% (95% CI 4.79% to 11.86%), as well as MDDs 26.24% (95% CI 21.02% to 32.22%) among homeless people. Our subgroup analysis showed that the prevalence of depressive symptoms was high among younger homeless people (<25 years of age), whereas the prevalence of MDD was high among older homeless people (>50 years of age) when compared with adults (25–50 years).ConclusionThis review showed that nearly half, one-fourth and one-tenth of homeless people are suffering from depressive symptoms, dysthymia and MDDs, respectively, which are notably higher than the reported prevalence rates in the general population. The findings suggest the need for appropriate mental health prevention and treatment strategies for this population group.

scholarly journals 2dFDR: a new approach to confounder adjustment substantially increases detection power in omics association studies

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sangyoon Yi ◽  
Xianyang Zhang ◽  
Lu Yang ◽  
Jinyan Huang ◽  
Yuanhang Liu ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Statistical Power ◽  
Association Studies ◽  
Control Procedure ◽  
Multiple Testing Correction ◽  
New Approach ◽  
False Discovery ◽  
Traditional Procedure ◽  
Extensive Evaluation ◽  
Confounder Adjustment

AbstractOne challenge facing omics association studies is the loss of statistical power when adjusting for confounders and multiple testing. The traditional statistical procedure involves fitting a confounder-adjusted regression model for each omics feature, followed by multiple testing correction. Here we show that the traditional procedure is not optimal and present a new approach, 2dFDR, a two-dimensional false discovery rate control procedure, for powerful confounder adjustment in multiple testing. Through extensive evaluation, we demonstrate that 2dFDR is more powerful than the traditional procedure, and in the presence of strong confounding and weak signals, the power improvement could be more than 100%.

scholarly journals Using the 11-item Version of the RCADS to Identify Anxiety and Depressive Disorders in Adolescents

2021 ◽  
Author(s):  
Jerica Radez ◽  
Polly Waite ◽  
Bruce Chorpita ◽  
Cathy Creswell ◽  
Faith Orchard ◽  
...  
Keyword(s):  
Suicidal Ideation ◽  
Depressive Disorders ◽  
Community Sample ◽  
Depression Scale ◽  
Parent Report ◽  
Depression Symptoms ◽  
Adolescent Report ◽  
Two Samples ◽  
Sensitivity Specificity ◽  
Anxiety Depression

AbstractThe purpose of this study was to identify items from the Revised Children’s Anxiety and Depression Scale – RCADS-C/P that provided a brief, reliable and valid screen for anxiety and/or depressive disorders in adolescents. In addition, we examined whether adding items assessing suicidal ideation (Moods and Feelings Questionnaire – MFQ- C/P) and symptom impact and duration (items adapted from the Strengths and Difficulties Questionnaire – SDQ) improved the identification of adolescents with anxiety and/or depressive disorders. We compared two samples of adolescents and their parents – a community sample, recruited through secondary schools in England (n = 214) and a clinic-referred sample, who met diagnostic criteria for anxiety and/or depressive disorder and were recruited through a university-based research clinic (n = 246). Participants completed the RCADS-C/P with additional symptom impact and duration items, and the MFQ-C/P. Using ROC curve analyses, we identified a set of 11 RCADS-C/P items (6 addressing anxiety and 5 depression symptoms) for adolescent- and parent-report. This set of 11 symptom items achieved sensitivity/specificity values > .75, which were comparable to corresponding values for the RCADS-47-C/P. Combining adolescent and parent-report improved the identification of anxiety/depression in adolescents compared to using adolescent-report alone. Finally, adding two symptom impact items further improved the sensitivity/specificity of the 11 symptom items, whereas adding suicidal ideation items did not. The 11 RCADS items accurately discriminated between the community and clinic-referred sample with anxiety and/or depressive disorders and have the potential to quickly and accurately identify adolescents with these disorders in community settings.

What are the reciprocal influences of randomized clinical trials and the patient–psychiatrist relationship?

1999 ◽  
Vol 14 (2) ◽  
pp. 93-100
Author(s):  
J. Catteau ◽  
C. Cyran ◽  
R. Bordet ◽  
C.E. Thomas ◽  
B.A. Dupuis
Keyword(s):  
Clinical Trials ◽  
Depressive Disorders ◽  
Randomized Clinical Trials ◽  
Antidepressant Drugs ◽  
Antidepressant Medication ◽  
Study Data ◽  
Phase Iii ◽  
Double Blind ◽  
Phase Iii Clinical Trials ◽  
Reciprocal Influences

SummaryThe goal of this prospective investigation was to study the course and the quality of patient-psychiatrist relationships during phase II / phase III clinical trials of antidepressant medication prescribed for depressive disorders. All patients who participated in the clinical trials (and subsequently in this survey) signed written informed consent statements and were subject to random double blind treatment assignment. Retrospective analysis of 118 investigations was carried out, and the patients involved were questioned concerning their experiences and impressions during and after the study. Data show that the outcome of clinical trials of antidepressant drugs are not a function of pre-existing good patient-psychiatrist relationships. On the other hand, no effects on the patient-psychiatrist relationship were found as a result of the experimental procedure, and it can be concluded that no detrimental effects on future patient-psychiatrist relationships were incurred.

scholarly journals NRG1 Genetic Variant Influences the Efficacy of Androgen-Deprivation Therapy in Men with Prostate Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 528
Author(s):  
Shu-Pin Huang ◽  
Yei-Tsung Chen ◽  
Lih-Chyang Chen ◽  
Cheng-Hsueh Lee ◽  
Chao-Yuan Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Tyrosine Kinases ◽  
Multiple Testing ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Androgen Deprivation ◽  
Nucleotide Polymorphisms ◽  
Multiple Testing Correction ◽  
Cancer Specific Survival

Neuregulins (NRGs) activate receptor tyrosine kinases of the ErbB family, and play essential roles in the proliferation, survival, and differentiation of normal and malignant tissue cells. We hypothesized that genetic variants of NRG signalling pathway genes may influence treatment outcomes in prostate cancer. To test this hypothesis, we performed a comprehensive analysis to evaluate the associations of 459 single-nucleotide polymorphisms in 19 NRG pathway genes with cancer-specific survival (CSS), overall survival (OS), and progression-free survival (PFS) in 630 patients with prostate cancer receiving androgen-deprivation therapy (ADT). After multivariate Cox regression and multiple testing correction, we found that NRG1 rs144160282 C > T is significantly associated with worsening CSS, OS, and PFS during ADT. Further analysis showed that low expression of NRG1 is closely related to prostate cancer, as indicated by a high Gleason score, an advanced stage, and a shorter PFS rate. Meta-analysis of 16 gene expression datasets of 1,081 prostate cancer samples and 294 adjacent normal samples indicate lower NRG1 expression in the former compared with the latter (p < 0.001). These results suggest that NRG1 rs144160282 might be a prognostic predictor of the efficacy of ADT. Further studies are required to confirm the significance of NRG1 as a biomarker and therapeutic target for prostate cancer.

scholarly journals Case-control study of adverse childhood experiences and multiple sclerosis risk and clinical outcomes

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262093
Author(s):  
Mary K. Horton ◽  
Shannon McCurdy ◽  
Xiaorong Shao ◽  
Kalliope Bellesis ◽  
Terrence Chinn ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcomes ◽  
Adverse Childhood Experiences ◽  
Multiple Testing ◽  
Multiple Testing Correction ◽  
Latent Factors ◽  
Childhood Experiences ◽  
Adverse Childhood ◽  
Rich Data ◽  
Control Study

Background Adverse childhood experiences (ACEs) are linked to numerous health conditions but understudied in multiple sclerosis (MS). This study’s objective was to test for the association between ACEs and MS risk and several clinical outcomes. Methods We used a sample of adult, non-Hispanic MS cases (n = 1422) and controls (n = 1185) from Northern California. Eighteen ACEs were assessed including parent divorce, parent death, and abuse. Outcomes included MS risk, age of MS onset, Multiple Sclerosis Severity Scale score, and use of a walking aid. Logistic and linear regression estimated odds ratios (ORs) (and beta coefficients) and 95% confidence intervals (CIs) for ACEs operationalized as any/none, counts, individual events, and latent factors/patterns. Results Overall, more MS cases experienced ≥1 ACE compared to controls (54.5% and 53.8%, respectively). After adjusting for sex, birthyear, and race, this small difference was attenuated (OR = 1.01, 95% CI: 0.87, 1.18). There were no trends of increasing or decreasing odds of MS across ACE count categories. Consistent associations between individual ACEs between ages 0–10 and 11–20 years and MS risk were not detected. Factor analysis identified five latent ACE factors, but their associations with MS risk were approximately null. Age of MS onset and other clinical outcomes were not associated with ACEs after multiple testing correction. Conclusion Despite rich data and multiple approaches to operationalizing ACEs, no consistent and statistically significant effects were observed between ACEs with MS. This highlights the challenges of studying sensitive, retrospective events among adults that occurred decades before data collection.

scholarly journals Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions

2018 ◽  
Author(s):  
David M. Howard ◽  
Mark J. Adams ◽  
Toni-Kim Clarke ◽  
Jonathan D. Hafferty ◽  
Jude Gibson ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Drug Repositioning ◽  
Association Studies ◽  
Meta Analysis ◽  
Enrichment Analysis ◽  
Brain Regions ◽  
Genome Wide Association Studies ◽  
Multiple Testing Correction ◽  
Synaptic Structure ◽  
Genome Wide

AbstractMajor depression is a debilitating psychiatric illness that is typically associated with low mood, anhedonia and a range of comorbidities. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximise sample size, we meta-analysed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 gene-sets associated with depression, including both genes and gene-pathways associated with synaptic structure and neurotransmission. Further evidence of the importance of prefrontal brain regions in depression was provided by an enrichment analysis. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant following multiple testing correction. Based on the putative genes associated with depression this work also highlights several potential drug repositioning opportunities. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding aetiology and developing new treatment approaches.

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