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The World Journal of Biological... Oct 2023Due to the common neurodevelopmental origin and easy accessibility, the retina serves as a surrogate marker for changes in the brain. Hence, Optical Coherence Tomography... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Due to the common neurodevelopmental origin and easy accessibility, the retina serves as a surrogate marker for changes in the brain. Hence, Optical Coherence Tomography (OCT), a tool to examine the neuronal layers of retina has gained importance in investigating psychiatric disorders. Several studies in the last decade have reported retinal structural alterations in schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). However, the findings are inconsistent. Hence, we conducted a meta-analysis to investigate alterations in OCT parameters in patients with SCZ, BD and MDD.
METHODS
We searched electronic databases for studies that examined OCT parameters in patients with SCZ, BD and MDD published up to January 2023. The primary outcome measures were thickness and volumes of the retinal Nerve Fibre Layer (RNFL). We conducted meta-analysis using a random effects model.
RESULTS
The searches yielded 2638 publications of which 43 studies were included in the final analysis across all disorders. Compared to controls, the RNFL was thinner in SCZ patients (SMD = -0.37, = <0.001) and BD patients (SMD = -0.67, = < 0.001), but not in MDD patients (SMD = -0.08, = 0.54). On quadrant wise analysis, temporal quadrant RNFL was thinner in SCZ but not in BD, while all other quadrants were thinner in both SCZ and BD.
CONCLUSION
We found significant reductions in RNFL thickness in SCZ and BD, but not in MDD. The differential involvement in various quadrants and parameters across the disorders has potential implications for using retinal parameters as a diagnostic biomarker.
Topics: Humans; Depressive Disorder, Major; Bipolar Disorder; Schizophrenia; Tomography, Optical Coherence; Brain
PubMed: 37070475
DOI: 10.1080/15622975.2023.2203231 -
Psychiatry Research Jan 2024Major depressive disorder (MDD) and postpartum depression (PPD) are common and burdensome conditions. This study aims to evaluate the efficacy and safety of zuranolone,... (Meta-Analysis)
Meta-Analysis Review
Major depressive disorder (MDD) and postpartum depression (PPD) are common and burdensome conditions. This study aims to evaluate the efficacy and safety of zuranolone, a neuroactive steroid γ-aminobutyric acid type A receptors-positive allosteric modulator, in treating MDD and PPD. A comprehensive literature search was conducted until September 2023, identifying seven randomized controlled trials (RCTs). The results demonstrated that zuranolone significantly decreased Hamilton Rating Scale for Depression (HAM-D) scores in patients with PPD or MDD at day 15 (concluding the 14-day course) and day 42-45 (4 weeks after treatment cessation) compared with the placebo, albeit exhibiting a diminishing trend. Moreover, a higher percentage of patients with PPD or MDD achieved HAM-D response and remission with zuranolone treatment compared with placebo at day 15. However, zuranolone did not significantly increase the proportion of MDD patients achieving HAM-D remission at 42/43 days. Adverse events (AEs) such as somnolence, dizziness, and sedation were linked to zuranolone, with a higher but not statistically significant rate of discontinuation due to AEs in the zuranolone group. Overall, our findings support the rapid antidepressant effects of zuranolone in MDD and PPD, along with a relatively favorable safety and tolerability. Large-scale longitudinal RCTs are needed to evaluate the long-term efficacy of zuranolone.
Topics: Female; Humans; Depression; Antidepressive Agents; Pregnanolone; Depressive Disorder, Major; Treatment Outcome; Double-Blind Method
PubMed: 38029628
DOI: 10.1016/j.psychres.2023.115640 -
Neuroscience and Biobehavioral Reviews Sep 2023Whether remitted major depressive disorder (rMDD) and MDD present common or distinct neuropathological mechanisms remains unclear. We performed a meta-analysis of... (Meta-Analysis)
Meta-Analysis Review
Common and distinct patterns of task-related neural activation abnormalities in patients with remitted and current major depressive disorder: A systematic review and coordinate-based meta-analysis.
Whether remitted major depressive disorder (rMDD) and MDD present common or distinct neuropathological mechanisms remains unclear. We performed a meta-analysis of task-related whole-brain functional magnetic resonance imaging (fMRI) using anisotropic effect-size signed differential mapping software to compare brain activation between rMDD/MDD patients and healthy controls (HCs). We included 18 rMDD studies (458 patients and 476 HCs) and 120 MDD studies (3746 patients and 3863 HCs). The results showed that MDD and rMDD patients shared increased neural activation in the right temporal pole and right superior temporal gyrus. Several brain regions, including the right middle temporal gyrus, left inferior parietal, prefrontal cortex, left superior frontal gyrus and striatum, differed significantly between MDD and rMDD. Meta-regression analyses revealed that the percentage of females with MDD was positively associated with brain activity in the right lenticular nucleus/putamen. Our results provide valuable insights into the underlying neuropathology of brain dysfunction in MDD, developing more targeted and efficacious treatment and intervention strategies, and more importantly, providing potential neuroimaging targets for the early screening of MDD.
Topics: Female; Humans; Depressive Disorder, Major; Brain; Brain Mapping; Prefrontal Cortex; Temporal Lobe; Magnetic Resonance Imaging
PubMed: 37315658
DOI: 10.1016/j.neubiorev.2023.105284 -
Journal of Affective Disorders Mar 2024Depression is a major cause of suicide and mortality worldwide. This study aims to conduct a systematic review to identify metabolic biomarkers and pathways for major... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Depression is a major cause of suicide and mortality worldwide. This study aims to conduct a systematic review to identify metabolic biomarkers and pathways for major depressive disorder (MDD), a prevalent subtype of clinical depression.
METHODS
We searched for metabolomics studies on depression published between January 2000 and January 2023 in the PubMed and Web of Science databases. The reported metabolic biomarkers were systematically evaluated and compared. Pathway analysis was implemented using MetaboAnalyst 5.0.
RESULTS
We included 26 clinical studies on MDD and 78 metabolomics studies on depressive-like animal models. A total of 55 and 77 high-frequency metabolites were reported consistently in two-thirds of clinical and murine studies, respectively. In the comparison between murine and clinical studies, we identified 9 consistently changed metabolites (tryptophan, tyrosine, phenylalanine, methionine, fumarate, valine, deoxycholic acid, pyruvate, kynurenic acid) in the blood, 1 consistently altered metabolite (indoxyl sulfate) in the urine and 14 disturbed metabolic pathways in both types of studies. These metabolic dysregulations and pathways are mainly implicated in enhanced inflammation, impaired neuroprotection, reduced energy metabolism, increased oxidative stress damage and disturbed apoptosis, laying solid molecular foundations for MDD.
LIMITATIONS
Due to unavailability of original data like effect-size results in many metabolomics studies, a meta-analysis cannot be conducted, and confounding factors cannot be fully ruled out.
CONCLUSIONS
This systematic review delineated metabolic biomarkers and pathways related to depression in the murine and clinical samples, providing opportunities for early diagnosis of MDD and the development of novel diagnostic targets.
Topics: Humans; Mice; Animals; Depressive Disorder, Major; Animal Experimentation; Depression; Biomarkers; Metabolomics
PubMed: 38211744
DOI: 10.1016/j.jad.2024.01.053 -
CNS Drugs Oct 2023A significant proportion of adults with major depressive disorder (MDD) do not respond to treatments which are currently used in clinical practice such as...
BACKGROUND
A significant proportion of adults with major depressive disorder (MDD) do not respond to treatments which are currently used in clinical practice such as first-generation monoamine-based antidepressants.
OBJECTIVES
The objective of this systematic review was to assess the efficacy, safety, and mechanisms of action of AXS-05, a combination of the NMDA-receptor antagonist dextromethorphan with bupropion, in adults with MDD.
METHODS
We searched PubMed, Embase, Google Scholar, and ClinicalTrials.gov for current studies reporting on efficacy and/or safety of AXS-05 in patients with MDD. The search terms included: "AXS-05" OR "dextromethorphan and bupropion" AND "depression". Studies from database inception to January 2023 were evaluated. Risk of bias was assessed using the Cochrane Risk of Bias tool.
RESULTS
The search yielded 54 studies of which 5 were included. All studies had low risk of bias. Depression severity, measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) significantly decreased as early as 1-week post-treatment from baseline when compared to a placebo-controlled group (LS mean difference 2.2; 95% CI 0.6-3.9; p = 0.007) and at 2 weeks compared to an active control group (LS mean difference 4.7; 95% CI 0.6-8.8; p = 0.024). Treatment efficacy could be maintained for up to 12 months with mean MADRS score reduction of 23 points from baseline. Clinical remission and response rates also improved at week 1 and were maintained for 12 months. The treatment was well-tolerated, with some transient adverse events reported.
CONCLUSION
Current evidence suggests that the combination of dextromethorphan and bupropion is a well-tolerated, rapid-acting treatment option for adults with MDD. Initial success with AXS-05 supports the mechanistic role of glutamatergeric and sigma 1 signaling in the pathophysiology of MDD.
Topics: Adult; Humans; Antidepressive Agents; Bupropion; Depression; Depressive Disorder, Major; Dextromethorphan; Clinical Trials as Topic
PubMed: 37792265
DOI: 10.1007/s40263-023-01032-5 -
Neuropsychopharmacology Reports Mar 2024This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy,... (Meta-Analysis)
Meta-Analysis
AIM
This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy, acceptability, tolerability, and safety profiles of brexpiprazole (BRE) and aripiprazole (ARI) for Japanese with major depressive disorder (MDD) who were inadequately responsive to antidepressants.
METHODS
Outcome measures were scores on the Montgomery Åsberg Depression Rating Scale (primary), the Clinical Global Impression severity scale, and social functioning scale; the non-response rate; the non-remission rate; all-cause discontinuation; discontinuation due to adverse events (DAE); at least one adverse event (1AE); serious adverse event, akathisia; tremor; weight gain.
RESULTS
A literature search identified three double-blind, randomized, placebo-controlled trials. These comprised one BRE study (with a 1 mg/day [BRE1] and a 2 mg/day [BRE2]) and two ARI studies (with a 3 mg/day arm and a flexible-dose arm[within the dosage range approved in Japan]) (n = 1736). Both BRE and ARI demonstrated better efficacy than the placebo. BRE but not ARI had a higher DAE than the placebo. ARI but not BRE had a higher 1AE than the placebo. BRE and ARI had a higher risk of akathisia and weight gain than the placebo. There were no significant differences between BRE and ARI for any of the outcomes. Although BRE1 had good efficacy, it carried risk of weight gain. Although BRE2 also had efficacy, it carried risks of DAE, akathisia, and weight gain. However, the risk of akathisia in BRE2 was reduced by an initial dose of 0.5 mg/day rather than 1.0 mg/day.
CONCLUSIONS
Overall BRE showed similar utility to ARI and a good risk-benefit balance.
Topics: Humans; Aripiprazole; Depressive Disorder, Major; Japan; Psychomotor Agitation; Network Meta-Analysis; Weight Gain; Randomized Controlled Trials as Topic; Thiophenes; Quinolones
PubMed: 38219278
DOI: 10.1002/npr2.12414 -
Journal of Affective Disorders Nov 2023This systematic review and meta-analysis aimed to explore whether early interventions can reduce affective symptoms and have long-term benefits among individuals at risk... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review and meta-analysis aimed to explore whether early interventions can reduce affective symptoms and have long-term benefits among individuals at risk of bipolar disorder (BD).
METHODS
The PubMed, Embase, and Web of Science databases were searched. The primary outcome was continuous symptom scores before and after treatment. Random effects meta-analyses were conducted for each outcome arm studied and pooled mean difference estimates were calculated.
RESULTS
The search identified 10 controlled studies involving 425 participants and 6 single-arm studies involving 90 participants. For controlled trials, meta-analysis showed that the interventions led to greater reduction in clinical global score than placebo (standardized mean differences (SMD) = -0.96, 95 % CI:-1.32, -0.60), and supported a long-term longitudinal effect for pharmacotherapy (SMD = -0.42, 95 % CI: -0.79, -0.05). For single-arm trials, both pharmacotherapy and psychotherapy showed efficacy for depressive symptoms, while pharmacotherapy only showed efficacy for hypomania symptoms (effect size (ES) = -9.16, 95 % CI:-11.29, -7.04). Discontinuation of pharmacotherapy due to adverse effects did not show a difference.
LIMITATIONS
The primary limitations are the small number of RCTs and the influence of medication dosage.
CONCLUSIONS
Based on the limited available data, early interventions show efficacy for individuals at risk of BD. Psychological therapy might be more beneficial for depressive symptoms and have long-term benefits for hypomania. Pharmacotherapy may be appropriate in situations of severe hypomanic symptoms and the poor functioning. Large, well-designed, double-blind -controlled trials are needed to make solid conclusions about the efficacy of early interventions.
Topics: Humans; Bipolar Disorder; Mania; Psychotherapy; Waiting Lists; Randomized Controlled Trials as Topic
PubMed: 37459972
DOI: 10.1016/j.jad.2023.07.021 -
International Journal of Clinical and... 2024Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder that impairs the cognitive function of individuals. Aerobic exercise stands out as a promising...
BACKGROUND
Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder that impairs the cognitive function of individuals. Aerobic exercise stands out as a promising non-pharmacological intervention for enhancing cognitive function and promoting brain health.While positive impacts of aerobic exercise on executive function in adults with depression have been documented, a comprehensive understanding of its benefits on overall cognitive function, including memory, attention, and processing speed, along with key moderating factors in adults with MDD, remains unexplored. The purpose of the systematic review and meta-analysis was to investigate the effects of aerobic exercise on overall cognitive function in adults with MDD, and to explore whether cognitive sub-domains, aerobic exercise characteristics, and study and sample variables modify the effects of aerobic exercise on cognition.
METHODS
Six English electronic databases (Embase, Cochrane Central, Scopus, APA PsycInfo, PubMed, Web of Science) were searched from inception to 2 April 2023. Randomized trials, including adults aged 18 years or above with a diagnosis of clinical depression, of the effects of aerobic exercise on cognitive function in adults with MDD compared to non-aerobic exercise groups were included. A three-level meta-analysis was conducted utilizing a random-effects model in R. The quality of the studies was evaluated using the Physiotherapy Evidence Database (PEDro) scale. The PROSPERO registration number is CRD42022367350.
RESULTS
Twelve randomized trials including 945 adults with MDD were included. Results indicated that aerobic exercise significantly improved overall cognitive function ( = 0.21; 95 % confidence intervals [CI] = 0.07, 0.34), and the sub-domains of memory ( = 0.25; 95 % CI = 0.06, 0.44) and executive function ( = 0.12; 95 % CI = 0.04, 0.20). Significant benefits in cognitive function were found from moderate-to-vigorous (mixed) intensity ( = 0.19; 95 % CI = 0.02, 0.37), aerobic exercise conducted 3 times per week ( = 0.23; 95 % CI = 0.10, 0.38), in sessions < 45 min ( = 0.59; 95 % CI = 0.28, 0.90), and 45-60 min ( = 0.16; 95 % CI = 0.07, 0.26), in aerobic exercise intervention ≤ 12 weeks ( = 0. 26; 95 % CI = 0.08, 0.44).
LIMITATIONS
This review only included peer-reviewed English-language studies, which may lead to a language bias. The results of the Egger's test suggested a potential publication bias.
CONCLUSIONS
Aerobic exercise is efficacious in improving overall cognitive function and the sub-domains of memory and executive function in adults with major depressive disorder.
PubMed: 38371396
DOI: 10.1016/j.ijchp.2024.100447 -
Translational Psychiatry Jun 2024Mapping brain-behaviour associations is paramount to understand and treat psychiatric disorders. Standard approaches involve investigating the association between one... (Review)
Review
Mapping brain-behaviour associations is paramount to understand and treat psychiatric disorders. Standard approaches involve investigating the association between one brain and one behavioural variable (univariate) or multiple variables against one brain/behaviour feature ('single' multivariate). Recently, large multimodal datasets have propelled a new wave of studies that leverage on 'doubly' multivariate approaches capable of parsing the multifaceted nature of both brain and behaviour simultaneously. Within this movement, canonical correlation analysis (CCA) and partial least squares (PLS) emerge as the most popular techniques. Both seek to capture shared information between brain and behaviour in the form of latent variables. We provide an overview of these methods, review the literature in psychiatric disorders, and discuss the main challenges from a predictive modelling perspective. We identified 39 studies across four diagnostic groups: attention deficit and hyperactive disorder (ADHD, k = 4, N = 569), autism spectrum disorders (ASD, k = 6, N = 1731), major depressive disorder (MDD, k = 5, N = 938), psychosis spectrum disorders (PSD, k = 13, N = 1150) and one transdiagnostic group (TD, k = 11, N = 5731). Most studies (67%) used CCA and focused on the association between either brain morphology, resting-state functional connectivity or fractional anisotropy against symptoms and/or cognition. There were three main findings. First, most diagnoses shared a link between clinical/cognitive symptoms and two brain measures, namely frontal morphology/brain activity and white matter association fibres (tracts between cortical areas in the same hemisphere). Second, typically less investigated behavioural variables in multivariate models such as physical health (e.g., BMI, drug use) and clinical history (e.g., childhood trauma) were identified as important features. Finally, most studies were at risk of bias due to low sample size/feature ratio and/or in-sample testing only. We highlight the importance of carefully mitigating these sources of bias with an exemplar application of CCA.
Topics: Humans; Brain; Mental Disorders; Autism Spectrum Disorder; Depressive Disorder, Major; Canonical Correlation Analysis; Attention Deficit Disorder with Hyperactivity; Least-Squares Analysis
PubMed: 38824172
DOI: 10.1038/s41398-024-02954-4 -
Journal of Affective Disorders Oct 2023A disruption of the kynurenine (KYN) pathway may exist in major depressive disorder (MDD). However, the changing pattern of the KYN pathway across the different disease... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A disruption of the kynurenine (KYN) pathway may exist in major depressive disorder (MDD). However, the changing pattern of the KYN pathway across the different disease states in MDD is unclear. Herein, we performed a meta-analysis to examine the differences in KYN metabolites between patients in the current episode of MDD (cMDD) and patients in remission (rMDD), as well as the changes after treatments.
METHODS
Literature was systematically searched from electronic databases, from inception up to September 2022. Random-effect models were used to quantify the differences in KYN metabolites between patients with MDD across acute depressive episode and remission phases, as well as the changes after treatments.
RESULTS
Fifty-one studies involving 7056 participants were included. Tryptophan (TRP), KYN, kynurenic acid (KYNA), KYNA/quinolinic acid (QA), KYNA/3-hydroxykynurenine (3-HK), and KYNA/KYN were significantly lower, while KYN/TRP was significantly higher in patients with cMDD. Moreover, these effect sizes were generally larger in medication-free patients. No significant differences were found between patients with rMDD and HCs. Additionally, KYNA was found negatively correlated with depression severity and significantly increased after treatments, while the alteration was not found in QA.
LIMITATIONS
The number of included studies of patients with rMDD and longitudinal studies investigating the change of the KYN metabolites after treatment with antidepressants was limited. In addition, the heterogeneity across included studies was relatively high.
CONCLUSIONS
These findings showed a comprehensive image of the unique dysfunction pattern of the KYN pathway across different MDD states and highlighted KYNA as a potentially sensitive biomarker of MDD.
Topics: Humans; Kynurenine; Depressive Disorder, Major; Tryptophan; Depression; Biomarkers; Kynurenic Acid; Quinolinic Acid
PubMed: 37467793
DOI: 10.1016/j.jad.2023.07.078