A metabolome-wide association study in the general population reveals decreased levels of serum laurylcarnitine in people with depression.
TL;DR: In this article, a metabolome-wide association analysis was conducted to investigate the link between the serum metabolome and depressed mood in 1411 participants of the KORA (Cooperative Health Research in the Augsburg Region) F4 study.
Abstract: Depression 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.
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TL;DR: In this paper, the authors investigated metabolic dysfunction on a systemic, cellular, and molecular level in unmedicated patients with major depressive disorder compared with matched healthy controls (HC) and found that despite comparable BMI scores and absence of cardiometabolic disease, patients with significant dyslipidemia.
11 citations
TL;DR: In this paper , the potential causal role of acylcarnitine metabolism in depression by leveraging genomics and Mendelian randomization was examined, and the association with depression was driven by the medium-chain acyclarnitines C8 (OR 1.04, 95%CIs 1.02-1.07) and C10 (OR = 1.06) and was confirmed in follow-up analyses using genetic instruments derived from a GWAS meta-analysis including up to 16,841 samples.
9 citations
TL;DR: In this article, a large multi-ethnic sample of 6838 participants aged 50 years old (mean age 62.4 ± 8.3 years) from West China Health and Aging Trend (WCHAT) study was analyzed.
8 citations
TL;DR: The most consistent evidence found was regarding kynurenine and acylcarnitine, which were identified as consistent with depression and response to treatment.
Abstract: Although the understanding of the pathophysiology of major depressive disorder (MDD) has advanced greatly, this has not been translated into improved outcomes. To date, no biomarkers have been identified for the diagnosis, prognosis, and therapeutic management of MDD. Thus, we aim to review the biomarkers that are differentially expressed in MDD. A systematic review was conducted in January 2022 in the PubMed/MEDLINE, Scopus, Embase, PsycINFO, and Gale Academic OneFile databases for clinical studies published from January 2001 onward using the following terms: “Depression” OR “Depressive disorder” AND “Metabolomic.” Multiple metabolites were found at altered levels in MDD, demonstrating the involvement of cellular signaling metabolites, components of the cell membrane, neurotransmitters, inflammatory and immunological mediators, hormone activators and precursors, and sleep controllers. Kynurenine and acylcarnitine were identified as consistent with depression and response to treatment. The most consistent evidence found was regarding kynurenine and acylcarnitine. Although the data obtained allow us to identify how metabolic pathways are affected in MDD, there is still not enough evidence to propose changes to current diagnostic and therapeutic actions. Some limitations are the heterogeneity of studies on metabolites, methods for detection, analyzed body fluids, and treatments used. The experiments contemplated in the review identified increased or reduced levels of metabolites, but not necessarily increased or reduced the activity of the associated pathways. The information acquired through metabolomic analyses does not specify whether the changes identified in the metabolites are a cause or a consequence of the pathology.
8 citations
TL;DR: In this article , a large multi-ethnic sample of 6838 participants aged 50 years old (mean age 62.4 ± 8.3 years) from West China Health and Aging Trend (WCHAT) study was analyzed.
8 citations
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TL;DR: In this paper, a different approach to problems of multiple significance testing is presented, which calls for controlling the expected proportion of falsely rejected hypotheses -the false discovery rate, which is equivalent to the FWER when all hypotheses are true but is smaller otherwise.
Abstract: SUMMARY The common approach to the multiplicity problem calls for controlling the familywise error rate (FWER). This approach, though, has faults, and we point out a few. A different approach to problems of multiple significance testing is presented. It calls for controlling the expected proportion of falsely rejected hypotheses -the false discovery rate. This error rate is equivalent to the FWER when all hypotheses are true but is smaller otherwise. Therefore, in problems where the control of the false discovery rate rather than that of the FWER is desired, there is potential for a gain in power. A simple sequential Bonferronitype procedure is proved to control the false discovery rate for independent test statistics, and a simulation study shows that the gain in power is substantial. The use of the new procedure and the appropriateness of the criterion are illustrated with examples.
83,420 citations
TL;DR: The study suggests that the PHQ has diagnostic validity comparable to the original clinician-administered PRIME-MD, and is more efficient to use.
Abstract: ContextThe Primary Care Evaluation of Mental Disorders (PRIME-MD) was developed
as a screening instrument but its administration time has limited its clinical
usefulness.ObjectiveTo determine if the self-administered PRIME-MD Patient Health Questionnaire
(PHQ) has validity and utility for diagnosing mental disorders in primary
care comparable to the original clinician-administered PRIME-MD.DesignCriterion standard study undertaken between May 1997 and November 1998.SettingEight primary care clinics in the United States.ParticipantsOf a total of 3000 adult patients (selected by site-specific methods
to avoid sampling bias) assessed by 62 primary care physicians (21 general
internal medicine, 41 family practice), 585 patients had an interview with
a mental health professional within 48 hours of completing the PHQ.Main Outcome MeasuresPatient Health Questionnaire diagnoses compared with independent diagnoses
made by mental health professionals; functional status measures; disability
days; health care use; and treatment/referral decisions.ResultsA total of 825 (28%) of the 3000 individuals and 170 (29%) of the 585
had a PHQ diagnosis. There was good agreement between PHQ diagnoses and those
of independent mental health professionals (for the diagnosis of any 1 or
more PHQ disorder, κ = 0.65; overall accuracy, 85%; sensitivity, 75%;
specificity, 90%), similar to the original PRIME-MD. Patients with PHQ diagnoses
had more functional impairment, disability days, and health care use than
did patients without PHQ diagnoses (for all group main effects, P<.001). The average time required of the physician to review the
PHQ was far less than to administer the original PRIME-MD (<3 minutes for
85% vs 16% of the cases). Although 80% of the physicians reported that routine
use of the PHQ would be useful, new management actions were initiated or planned
for only 117 (32%) of the 363 patients with 1 or more PHQ diagnoses not previously
recognized.ConclusionOur study suggests that the PHQ has diagnostic validity comparable to
the original clinician-administered PRIME-MD, and is more efficient to use.
7,444 citations
TL;DR: This year's update to the HMDB, HMDB 4.0, represents the most significant upgrade to the database in its history and should greatly enhance its ease of use and its potential applications in nutrition, biochemistry, clinical chemistry, clinical genetics, medicine, and metabolomics science.
Abstract: The Human Metabolome Database or HMDB (www.hmdb.ca) is a web-enabled metabolomic database containing comprehensive information about human metabolites along with their biological roles, physiological concentrations, disease associations, chemical reactions, metabolic pathways, and reference spectra. First described in 2007, the HMDB is now considered the standard metabolomic resource for human metabolic studies. Over the past decade the HMDB has continued to grow and evolve in response to emerging needs for metabolomics researchers and continuing changes in web standards. This year's update, HMDB 4.0, represents the most significant upgrade to the database in its history. For instance, the number of fully annotated metabolites has increased by nearly threefold, the number of experimental spectra has grown by almost fourfold and the number of illustrated metabolic pathways has grown by a factor of almost 60. Significant improvements have also been made to the HMDB's chemical taxonomy, chemical ontology, spectral viewing, and spectral/text searching tools. A great deal of brand new data has also been added to HMDB 4.0. This includes large quantities of predicted MS/MS and GC-MS reference spectral data as well as predicted (physiologically feasible) metabolite structures to facilitate novel metabolite identification. Additional information on metabolite-SNP interactions and the influence of drugs on metabolite levels (pharmacometabolomics) has also been added. Many other important improvements in the content, the interface, and the performance of the HMDB website have been made and these should greatly enhance its ease of use and its potential applications in nutrition, biochemistry, clinical chemistry, clinical genetics, medicine, and metabolomics science.
2,608 citations
TL;DR: The authors present severity proportions; burden by country, region, age, sex, and year; as well as burden of depressive disorders as a risk factor for suicide and ischemic heart disease.
Abstract: Background: Depressive disorders were a leading cause of burden in the Global Burden of Disease (GBD) 1990 and 2000 studies. Here, we analyze the burden of depressive disorders in GBD 2010 and present severity proportions, burden by country, region, age, sex, and year, as well as burden of depressive disorders as a risk factor for suicide and ischemic heart disease. Methods and Findings: Burden was calculated for major depressive disorder (MDD) and dysthymia. A systematic review of epidemiological data was conducted. The data were pooled using a Bayesian meta-regression. Disability weights from population survey data quantified the severity of health loss from depressive disorders. These weights were used to calculate years lived with disability (YLDs) and disability adjusted life years (DALYs). Separate DALYs were estimated for suicide and ischemic heart disease attributable to depressive disorders. Depressive disorders were the second leading cause of YLDs in 2010. MDD accounted for 8.2% (5.9%–10.8%) of global YLDs and dysthymia for 1.4% (0.9%–2.0%). Depressive disorders were a leading cause of DALYs even though no mortality was attributed to them as the underlying cause. MDD accounted for 2.5% (1.9%–3.2%) of global DALYs and dysthymia for 0.5% (0.3%–0.6%). There was more regional variation in burden for MDD than for dysthymia; with higher estimates in females, and adults of working age. Whilst burden increased by 37.5% between 1990 and 2010, this was due to population growth and ageing. MDD explained 16 million suicide DALYs and almost 4 million ischemic heart disease DALYs. This attributable burden would increase the overall burden of depressive disorders from 3.0% (2.2%–3.8%) to 3.8% (3.0%–4.7%) of global DALYs. Conclusions: GBD 2010 identified depressive disorders as a leading cause of burden. MDD was also a contributor of burden allocated to suicide and ischemic heart disease. These findings emphasize the importance of including depressive disorders as a public-health priority and implementing cost-effective interventions to reduce its burden. Please see later in the article for the Editors’ Summary.
2,240 citations
TL;DR: The ability of the PHQ-9 to detect depression outcome and changes over time is demonstrated in three groups of patients whose depression status either improved, remained unchanged, or deteriorated over time.
1,207 citations