Endocannabinoid signaling in the etiology and treatment of major depressive illness.
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ABSTRACT:
SUBMITTER: Hillard CJ
PROVIDER: S-EPMC4002665 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
Endocannabinoid signaling in the etiology and treatment of major depressive illness.
Hillard Cecilia J CJ Liu Qing-song QS
Current pharmaceutical design 20140101 23
The purpose of this review is to examine human and preclinical data that are relevant to the following hypotheses. The first hypothesis is that deficient CB1R-mediated signaling results in symptoms that mimic those seen in depression. The second hypothesis is that activation of CB1R-mediated signaling results in behavioral, endocrine and other effects that are similar to those produced by currently used antidepressants. The third hypothesis is that conventional antidepressant therapies act throu ...[more]
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Project description:ObjectiveReducing unsuccessful treatment trials could improve depression treatment. Quantitative EEG (QEEG) may predict treatment response and is being commercially marketed for this purpose. The authors sought to quantify the reliability of QEEG for response prediction in depressive illness and to identify methodological limitations of the available evidence.MethodThe authors conducted a meta-analysis of diagnostic accuracy for QEEG in depressive illness, based on articles published between January 2000 and November 2017. The review included all articles that used QEEG to predict response during a major depressive episode, regardless of patient population, treatment, or QEEG marker. The primary meta-analytic outcome was the accuracy for predicting response to depression treatment, expressed as sensitivity, specificity, and the logarithm of the diagnostic odds ratio. Raters also judged each article on indicators of good research practice.ResultsIn 76 articles reporting 81 biomarkers, the meta-analytic estimates showed a sensitivity of 0.72 (95% CI=0.67-0.76) and a specificity of 0.68 (95% CI=0.63-0.73). The logarithm of the diagnostic odds ratio was 1.89 (95% CI=1.56-2.21), and the area under the receiver operator curve was 0.76 (95% CI=0.71-0.80). No specific QEEG biomarker or specific treatment showed greater predictive power than the all-studies estimate in a meta-regression. Funnel plot analysis suggested substantial publication bias. Most studies did not use ideal practices.ConclusionsQEEG does not appear to be clinically reliable for predicting depression treatment response, as the literature is limited by underreporting of negative results, a lack of out-of-sample validation, and insufficient direct replication of previous findings. Until these limitations are remedied, QEEG is not recommended for guiding selection of psychiatric treatment.
| S-EPMC6312739 | biostudies-literature
Project description:The endocannabinoid (eCB) system is implicated in the pathophysiology of depression and is responsive to acute exercise in healthy adults.PurposeWe aimed to describe acute changes in serum eCB across a prescribed moderate (MOD) and a self-selected/preferred (PREF) intensity exercise session in women with major depressive disorder (MDD) and determine relationships between changes in eCB and mood states.MethodsWomen with MDD (n = 17) exercised in separate sessions for 20 min on a cycle ergometer at both MOD or PREF in a within-subjects design. Blood was drawn before and within 10 min after exercise. Serum concentrations of eCB (anandamide [AEA], 2-arachidonoylglycerol) and related lipids (palmitoylethanolamine, oleoylethanolamine, 2-oleoylglycerol) were quantified using stable isotope-dilution, liquid chromatography/mass spectrometry/mass spectrometry. The profile of mood states and state-trait anxiety inventory (state only) were completed before, 10 min and 30 min postexercise.ResultsSignificant elevations in AEA (P = 0.013) and oleoylethanolamine (P = 0.024) occurred for MOD (moderate effect sizes: Cohen's d = 0.58 and 0.41, respectively). Significant (P < 0.05) moderate negative associations existed between changes in AEA and mood states for MOD at 10 min (depression, confusion, fatigue, total mood disturbance [TMD] and state anxiety) and 30 min postexercise (confusion, TMD and state anxiety). Significant (P < 0.05) moderate negative associations existed between 2-arachidonoylglycerol and mood states at 10 min (depression and confusion) and 30 min postexercise (confusion and TMD). Changes in eCB or related lipids or eCB-mood relationships were not found for PREF.ConclusionGiven the broad, moderate-strength relationships between improvements in mood states and eCB increases after MOD, it is plausible that the eCB system contributes to the mood-enhancing effects of prescribed acute exercise in MDD. Alternative mechanisms are likely involved in the positive mood state effects of preferred exercise.
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Project description:BackgroundMajor depressive disorder, a highly prevalent mental health condition, can be challenging to treat.ObjectiveWe aimed to characterize treatment patterns within and across multiple major depressive episodes in patients receiving treatment for major depressive disorder.MethodsAdults with newly diagnosed major depressive disorder and one or more major depressive episodes were identified using the IBM® MarketScan® Commercial database. Eligible patients had 12 months of continuous enrollment before and after diagnosis. Lines of therapy were periods of continuous treatment with one or more antidepressant claims. Antidepressant, atypical antipsychotic, or mood stabilizer regimens as monotherapy or adjunctive therapy were characterized by lines of therapy and major depressive episodes. Descriptive analyses were performed.ResultsA total of 455,082 patients were included in the analysis. The majority of treatment regimens were monotherapy, which decreased with subsequent lines of therapy, while adjunctive treatments increased with subsequent lines of therapy. There were 1860 unique adjunctive regimens identified. Of the 40,315 patients (9%) who received adjunctive therapy, 8024 (20%; 2% of all patients) received atypical antipsychotic-adjunctive regimens. Only 19% of patients treated with atypical antipsychotic-adjunctive therapy discontinued treatment versus 42% of monotherapy-treated patients. On average, patients who received an adjunctive atypical antipsychotic received it as their third line of therapy and approximately 400 days after the initial antidepressant treatment.ConclusionsIn this study, many patients continued monotherapy major depressive disorder regimens and experienced multiple treatment changes. Few patients were treated with adjunctive therapy. These results suggest underutilization of potentially effective treatments, which represents an opportunity to optimize the treatment of patients with major depressive disorder.
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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