OBJECTIVE: Major Depressive Disorder (MDD) is characterized by persistent symptoms such as fatigue, loss of interest in activities, feelings of sadness and worthlessness. MDD often coexist with cardiovascular disease (CVD), yet the precise link between these conditions remains unclear. This review explores factors underlying the development of MDD and CVD, including genetic, epigenetic, platelet activation, inflammation, hypothalamic-pituitary-adrenal (HPA) axis activation, endothelial cell (EC) dysfunction, and blood-brain barrier (BBB) disruption.
RESULTS: Single nucleotide polymorphisms (SNPs) in the membrane-associated guanylate kinase WW and PDZ domain-containing protein 1 (MAGI-1) are associated with neuroticism and psychiatric disorders including MDD. SNPs in MAGI-1 are also linked to chronic inflammatory disorders such as spontaneous glomerulosclerosis, celiac disease, ulcerative colitis, and Crohn\'s disease. Increased MAGI-1 expression has been observed in colonic epithelial samples from Crohn\'s disease and ulcerative colitis patients. MAGI-1 also plays a role in regulating EC activation and atherogenesis in mice and is essential for Influenza A virus (IAV) infection, endoplasmic reticulum stress-induced EC apoptosis, and thrombin-induced EC permeability. Despite being understudied in human disease; evidence suggests that MAGI-1 may play a role in linking CVD and MDD. Therefore, further investigation of MAG-1 could be warranted to elucidate its potential involvement in these conditions.

OBJECTIVE: Major depressive disorder (MDD) is a prevalent psychiatric condition and vortioxetine offers promising antidepressant effects due to its unique pharmacological profile. However, the dose-response relationships of vortioxetine for MDD is not well established. We aimed to conduct dose-response meta-analyses to fill this gap.
METHODS: We systematically searched multiple electronic databases for randomized controlled trials of vortioxetine for MDD, with the last search conducted on 08 February, 2024. The dose-response relationship was evaluated using a one-stage random-effects dose-response meta-analysis with restricted cubic spline model. The primary outcome was efficacy (mean change in depression scale score), with secondary outcomes including response, dropout for any reasons (acceptability), dropout for adverse events (tolerability), and any adverse events (safety).
RESULTS: The dose-response meta-analysis comprised 16 studies, with 4,294 participants allocated to the vortioxetine group and 2,299 participants allocated to the placebo group. The estimated 50% effective dose was 4.37 mg/day, and the near-maximal effective dose (95% effective dose) was 17.93 mg/day. Visual inspection of the dose-efficacy curve suggests that a plateau possibly had not been reached yet at 20 mg/day. Acceptability, tolerability and safety decreased as the dose increased. Subgroup analysis indicated that no significant differences were observed in acceptability, tolerability and safety among the dosage groups.
CONCLUSIONS: Vortioxetine may potentially provide additional therapeutic benefits when exceeding the current licensed dosage without significantly impacting safety. Conducting clinical trials exceeding the current approved dosage appears necessary to fully comprehend its efficacy and risk.

UNASSIGNED: This randomized, placebo-controlled, double-blind, parallel study aimed to evaluate the effect of 3-month supplementation of bovine colostrum (BOV-COL; 8x400 mg per day) on the outcomes of depression treatment in hospitalized patients with substance use disorder (SUD). The hypothesis is that BOV-COL supplementation as an add-on treatment results in favorable alternations in selected blood inflammatory markers or neurotransmitters, leading to better depression treatment outcomes compared with placebo (PLA).
UNASSIGNED: Patients with a Minnesota Multiphasic Personality Inventory-2 score ≥60 points were enrolled. Twenty-nine participants (n=18 in the BOV-COL group and n=11 in the PLA group) completed the protocol.
UNASSIGNED: The mean Beck Depression Inventory-II score was significantly reduced after supplementation in both groups. However, the mean 17-point Hamilton Depression Rating Scale score was decreased in the BOV-COL group, but not in the PLA group. In the BOV-COL group, there was a reduction in interleukin (IL)-1, IL-6, IL-10, the IL-6:IL-10 ratio, IL-17, and tumor necrosis factor alpha (TNF-α), while in the PLA group only IL-6 decreased. Favorable alternations in the total count and differentials of white blood cell subsets were more pronounced in the BOV-COL. There were no changes in neurotransmitter concentrations.
UNASSIGNED: BOV-COL supplementation is a promising add-on therapy in patients with depression and SUD.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin\'s acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression.
METHODS: Fifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures.
CONCLUSIONS: This study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin\'s antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response.
BACKGROUND: ClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.

In ESCAPE-TRD (NCT04338321), esketamine nasal spray (NS) significantly increased the probability of remission at Week 8, and of being relapse-free through Week 32 after remission at Week 8, versus quetiapine extended release (XR) in patients with treatment resistant depression (TRD). Here, we explore the time course, burden and consequences of treatment emergent adverse events (TEAEs) in the phase IIIb ESCAPE‑TRD trial. Patients with TRD were randomised 1:1 to esketamine NS or quetiapine XR, dosed per label alongside an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. In this secondary publication, safety analyses (comprising patients who received ≥1 dose of study treatment) included incidence, severity and durations (Kaplan‑Meier method) of TEAEs, and subsequent dispositional changes. P values were not adjusted for multiple testing. 336 patients were randomised to esketamine NS and 340 to quetiapine XR; 334 and 336 received ≥1 dose of study treatment, respectively. TEAEs were significantly more common with esketamine NS than quetiapine XR (91.9 % versus 78.0 %; p < 0.001), but were typically mild/moderate and transient in nature: a greater proportion resolved on the same-day (92.0 % versus 12.1 %) and lead to treatment discontinuation in significantly fewer patients (4.2 % versus 11.0 %, respectively; p < 0.001). The proportion of days spent with TEAEs was significantly lower with esketamine NS than quetiapine XR (median: 11.9 % versus 21.3 %; p < 0.001). Although more frequent with esketamine NS, TEAEs were typically transient and mild, with discontinuation less likely versus quetiapine XR. Data were consistent with established safety profiles, with no new safety signals identified. Alongside greater efficacy, the demonstrably more favourable tolerability profile of esketamine NS versus quetiapine XR further supports its use for TRD.

UNASSIGNED: Sleep is associated with psychiatric disorders. However, their causality remains unknown.
UNASSIGNED: The study explored the causal relationship between seven sleep parameters (sleep duration, insomnia, sleep apnea, chronotype, daytime dozing, napping during the day, and snoring) and three psychiatric disorders including major depressive disorder (MDD), schizophrenia, and attention-deficit/hyperactivity disorder (ADHD) using two-sample Mendelian randomization (MR). Genome-wide association study (GWAS) summary data for sleep parameters were obtained from the United Kingdom biobank, FinnGen biobank, and EBI databases. MR-Egger, weighted median, inverse-variance weighted (IVW), simple mode, weighted mode, maximum likelihood, penalized weighted median, and IVW(fixed effects) were used to perform the MR analysis. The heterogeneity was detected by Cochran\'s Q statistic. The horizontal pleiotropy was detected by MR Egger. The sensitivity was investigated by the leave-one-out analysis.
UNASSIGNED: Insomnia (OR = 2.02, 95%CI = 1.34-3.03, p = 0.001, False-discovery rate (FDR) corrected p-value = 0.011) and napping during the day (OR = 1.81, 95%CI = 1.34-2.44, FDR corrected p-value<0.001) were associated with an increased risk of MDD. Longer sleep duration (OR = 2.20, 95%CI = 1.24-3.90, FDR corrected p-value = 0.049) had an association with the increased risk of schizophrenia, while daytime dozing (OR = 4.44, 95%CI = 1.20-16.41, corrected p-value = 0.088)and napping during the day (OR = 2.11, 95%CI = 1.11-4.02, FDR corrected p-value = 0.088) had a suggestive association with an increased risk of schizophrenia. Longer sleep duration had a suggestive association with a decreased risk of ADHD (OR = 0.66, 95%CI = 0.42-0.93, FDR corrected p-value = 0.088).
UNASSIGNED: This study provides further evidence for a complex relationship between sleep and psychiatric disorders. Our findings highlight the potential benefits of addressing sleep problems in the prevention of psychiatric disorders.

Ketamine, a pharmacological agent that acts as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, has garnered considerable interest because of its notable and expeditious antidepressant properties observed in individuals diagnosed with major depressive disorder (MDD) who exhibit resistance to conventional therapeutic interventions. A comprehensive and rigorous systematic review was undertaken to evaluate the prevalence of ketamine abuse undergoing ketamine treatment for depressive disorders. A comprehensive search was conducted across the electronic databases to identify pertinent studies published between 2021 and 2023. The present investigation incorporated a comprehensive range of studies encompassing the abuse or misuse of ketamine, including case reports, observational studies, and clinical trials. Data extraction and quality assessment were conducted in accordance with predetermined criteria. The findings of this systematic review demonstrate the importance of monitoring and addressing ketamine abuse in patients receiving ketamine treatment for depressive disorders like MDD. The wide range of reported prevalence rates highlights the need for standardized criteria and measures for defining and assessing ketamine abuse. This study presents a significant contribution to the field by introducing a novel screening questionnaire and assessment algorithm designed to identify and evaluate ketamine misuse among major depressive disorder (MDD) patients undergoing ketamine treatment. This innovative tool holds the potential to enhance clinical practice by providing healthcare professionals with a standardized approach to promptly detect and address ketamine misuse. The integration of this screening tool into routine care protocols can facilitate more effective monitoring and management of ketamine misuse in this population, ultimately leading to improved patient outcomes and safety.

UNASSIGNED: Posttraumatic stress disorder (PTSD) is still-underdiagnosed and often accompanied by other psychiatric disorders affecting treatment and outcomes.
UNASSIGNED: Here we present a case report of a 28-year-old female patient with comorbid PTSD, major depressive disorder (MDD), and anorexia nervosa (AN). The patient had been treated with various medications and attended trauma-focused psychotherapy. Because none of these treatments yielded satisfying improvement, the patient was referred for electroconvulsive therapy (ECT). We had to overcome challenges such as the patient\'s false assumptions about ECT, the simultaneous use of benzodiazepines and the management of the side effects of ECT. The symptoms of MDD and PTSD improved after 12 treatment sessions.
UNASSIGNED: Our report suggests that ECT may be a safe and effective method for treating patients with PTSD and comorbid MDD and AN.

UNASSIGNED: Alterations in the level of neurotransmitters are evident in patients with major depressive disorder (MDD). Vitamin B12 mediates the synthesis of neurotransmitters, and hence, vitamin B12 deficiency could be associated with depression.
UNASSIGNED: To assess the levels of serum vitamin B12, homocysteine (Hcy), and haematological profiles in patients of MDD.
UNASSIGNED: Fifty-nine patients with MDD were recruited based on ICD-10 criteria. Severity of depression was assessed by HAM-D scale. Vitamin B12, Hcy levels, and haematological profiles were analysed.
UNASSIGNED: Vitamin B12 was deficient or depleted in all patients with MDD. The median level of vitamin B12 in serum was 164.2 pg./ml and significantly lower in patients with severe MDD. The mean value of Hcy was 18.34 μmol/L, which was high compared to the normal reference range. The red cell distribution width (RDW-CV) varied significantly between the three groups of MDD patients. Patients consuming non-vegetarian food had a significantly higher median value of serum vitamin B12.
UNASSIGNED: Vitamin B12 deficiency is found in patients with MDD and varies inversely with severity of MDD. Hcy is found to be higher in patients with MDD. The manifestation of depressive symptoms precedes the more commonly known haematological manifestations of vitamin B12 deficiency in this study.

暂无摘要。