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BMJ Open May 2024Late-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a...
INTRODUCTION
Late-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a risk factor for cognitive decline. Slow wave sleep (SWS) has been implicated in key processes including synaptic plasticity and memory. A deficiency in SWS may be a core component of depression pathophysiology. The anaesthetic propofol can induce electroencephalographic (EEG) slow waves that resemble SWS. Propofol may enhance SWS and oral antidepressant therapy, but relationships are unclear. We hypothesise that propofol infusions will enhance SWS and improve depression in older adults with LL-TRD. This hypothesis has been supported by a recent small case series.
METHODS AND ANALYSIS
SWIPED (Slow Wave Induction by Propofol to Eliminate Depression) phase I is an ongoing open-label, single-arm trial that assesses the safety and feasibility of using propofol to enhance SWS in older adults with LL-TRD. The study is enrolling 15 English-speaking adults over age 60 with LL-TRD. Participants will receive two propofol infusions 2-6 days apart. Propofol infusions are individually titrated to maximise the expression of EEG slow waves. Preinfusion and postinfusion sleep architecture are evaluated through at-home overnight EEG recordings acquired using a wireless headband equipped with dry electrodes. Sleep EEG recordings are scored manually. Key EEG measures include sleep slow wave activity, SWS duration and delta sleep ratio. Longitudinal changes in depression, suicidality and anhedonia are assessed. Assessments are performed prior to the first infusion and up to 10 weeks after the second infusion. Cognitive ability is assessed at enrolment and approximately 3 weeks after the second infusion.
ETHICS AND DISSEMINATION
The study was approved by the Washington University Human Research Protection Office. Recruitment began in November 2022. Dissemination plans include presentations at scientific conferences, peer-reviewed publications and mass media. Positive results will lead to a larger phase II randomised placebo-controlled trial.
TRIAL REGISTRATION NUMBER
NCT04680910.
Topics: Humans; Propofol; Cognitive Dysfunction; Aged; Sleep, Slow-Wave; Electroencephalography; Male; Anesthetics, Intravenous; Depressive Disorder, Treatment-Resistant; Female; Middle Aged; Clinical Trials, Phase I as Topic
PubMed: 38816055
DOI: 10.1136/bmjopen-2024-087516 -
BMJ Open May 2024Depressed mood is a psychological state characterised by sadness or loss of interest in activities. Depressed mood is a highly prevalent symptom across major mental... (Review)
Review
INTRODUCTION
Depressed mood is a psychological state characterised by sadness or loss of interest in activities. Depressed mood is a highly prevalent symptom across major mental disorders. However, there is limited understanding of the burden and management of comorbid depressed mood across major mental disorders. Therefore, this scoping review aims to summarise knowledge on depressed mood among persons with anxiety and/or psychosis. The specific aims are to describe the epidemiology and risk factors of depressed mood as a transdiagnostic target among persons with anxiety and/or psychosis, to identify commonly used outcome measures for depressed mood and to outline initial evidence of psychometric robustness and to identify and summarise the effectiveness of commonly applied depressed mood modification interventions. Our hope is that the proposed review will provide insights into the burden of depressed mood in persons with anxiety and psychosis and help to identify evidence gaps and recommendations for future research.
METHODS AND ANALYSIS
This scoping review will be conducted per Arksey and O'Malley's framework. We will first search for peer-reviewed articles and grey literature published from 2004 to 2023 in PubMed, Scopus, Web of Science, Africa-Wide Information, CINAHL, PsycINFO, Academic Search Premier, Humanities International Complete, Sabinet, SocINDEX, Open Grey and Google Scholar. We will include articles reporting depressed mood (subthreshold depression) among persons with anxiety and/or psychosis. Studies recruiting participants meeting depression diagnostic criteria and those published in non-English languages will be excluded. Two independent researchers will extract the data. We will analyse and chart data collaboratively with researchers with lived experiences of depressed mood.
ETHICS AND DISSEMINATION
This study does not require ethical approval as it is a literature review. The results will be submitted for publication in a peer-reviewed journal.
Topics: Humans; Psychotic Disorders; Depression; Research Design; Review Literature as Topic; Anxiety Disorders; Anxiety
PubMed: 38816047
DOI: 10.1136/bmjopen-2023-077695 -
Psychiatrike = Psychiatriki May 2024Esketamine is a non-selective, competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor in the brain. Through NMDA receptor antagonism, esketamine causes a...
Esketamine is a non-selective, competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor in the brain. Through NMDA receptor antagonism, esketamine causes a transient increase in glutamate release, leading to increases in neurotrophic signaling and restoration of synaptic function in brain regions involved in mood regulation and emotional behavior. Several randomized clinical trials have shown its effectiveness in reducing the symptoms of depression in some people, despite its short-term side effects that include mainly disorientation, dizziness, nausea, and increased blood pressure. In 2019, the United States Food and Drug Administration (FDA) as well as the European Medicines Agency approved the use of esketamine nasal spray in combination with an oral antidepressant for treatment-resistant depression in adults. Our study aimed to evaluate the effectiveness of this new therapeutic proposal in a case series of five Greek patients with treatment- resistant depression. Intranasal esketamine was administered under medical supervision in combination with an oral antidepressant. Depressive symptoms were evaluated at three time points (baseline, end of treatment, and one-year post-treatment) using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Patient Health Questionnaire (PHQ-9), the CGI Clinical Global Impression Scale, and the Perceived Deficits Questionnaire for Depression (PDQ-D). Possible side effects were assessed using the Richmond Suppression Agitation Scale (RASS), the Sheehan Disability Scale (SDS), the CADSS Disruptive States Scale, and a predefined list of adverse events (AEs) and serious adverse events (SAEs). Patients followed an individualized treatment plan for seven to twelve months depending on the achievement of an adequate response. Statistical analysis of the results revealed a significant improvement (p<0.05) on all scales used. All participants maintained their level of improvement at follow-up after twelve months. Adverse effects were found to be mild and tolerable. It is worth noting that significant side effects were reported only by the two patients with comorbid personality disorder. The results, despite limited to a small sample, indicate the positive effect of esketamine on the stable reduction of depressive symptoms among patients with resistant depression, even after the completion of treatment.
PubMed: 38814267
DOI: 10.22365/jpsych.2024.006 -
EClinicalMedicine May 2024Postpartum blues (PPB) is a frequent syndrome of sad mood, crying spells, anxiety, restlessness, reduced appetite, and irritability, typically peaking day 5 postpartum....
BACKGROUND
Postpartum blues (PPB) is a frequent syndrome of sad mood, crying spells, anxiety, restlessness, reduced appetite, and irritability, typically peaking day 5 postpartum. When severe, it greatly increases risk for later postpartum depression. This trial compared a dietary supplement to placebo on PPB severity. The supplement was designed to counter downstream effects of elevated monoamine oxidase A level, implicated in causing PPB.
METHODS
Participants recruited by advertisement from the Toronto region completed procedures at CAMH, Canada and/or participants' homes. Oral supplement or identical appearing relatively inert placebo were administered in randomised, double-blind fashion. Supplement was blueberry juice and extract given four times between nighttime day 3 and morning day 5 postpartum; tryptophan 2 g nighttime day 4 postpartum, and tyrosine 10 g morning day 5 postpartum. On day 5, depressed mood induction procedure (MIP) and postpartum blues were assessed. All data is presented (NCT03296956 closed, clinicaltrials.gov).
FINDINGS
Between January 2019 and December 2022, participants took supplement (n = 51) or placebo (n = 52). There was no significant effect on primary outcome MIP on visual analogue scale for depressed mood (mean difference = -0.39 mm, 95% CI: -6.42 to 5.65 mm). Stein Maternity Blues scores, exploratory PPB measure, was lower in the active group (effect size 0.62; median, interquartile range (IQR): active 2.00 (IQR 1, 4); placebo 4.00 (IQR 1.5, 6); regression with general linear model, supplement effect, β coefficient = -1.50 (95%: CI -2.60, -0.40), p = 0.008; effect of CES-D crying category before supplement, p = 0.03-0.00000023). Twenty-six and 40 different adverse events occurred within 25% and 42% of supplement and placebo cases respectively (Chi-Square, p = 0.06).
INTERPRETATION
The primary outcome was negative for effect on depressed mood induction, however the supplement moderately reduced PPB.
FUNDING
CAMH/Exeltis.
PubMed: 38813444
DOI: 10.1016/j.eclinm.2024.102593 -
BMC Psychiatry May 2024Cerebral resting-state networks were suggested to be strongly associated with depressive disorders. However, the causal relationship between cerebral networks and...
BACKGROUND
Cerebral resting-state networks were suggested to be strongly associated with depressive disorders. However, the causal relationship between cerebral networks and depressive disorders remains controversial. In this study, we aimed to investigate the effect of resting-state networks on depressive disorders using a bidirectional Mendelian randomization (MR) design.
METHODS
Updated summary-level genome-wide association study (GWAS) data correlated with resting-state networks were obtained from a meta-analysis of European-descent GWAS from the Complex Trait Genetics Lab. Depression-related GWAS data were obtained from the FinnGen study involving participants with European ancestry. Resting-state functional magnetic resonance imaging and multiband diffusion imaging of the brain were performed to measure functional and structural connectivity in seven well-known networks. Inverse-variance weighting was used as the primary estimate, whereas the MR-Pleiotropy RESidual Sum and Outliers (PRESSO), MR-Egger, and weighted median were used to detect heterogeneity, sensitivity, and pleiotropy.
RESULTS
In total, 20,928 functional and 20,573 structural connectivity data as well as depression-related GWAS data from 48,847 patients and 225,483 controls were analyzed. Evidence for a causal effect of the structural limbic network on depressive disorders was found in the inverse variance-weighted limbic network (odds ratio, [Formula: see text]; 95% confidence interval, [Formula: see text]; [Formula: see text]), whereas the causal effect of depressive disorders on SC LN was not found(OR=1.0025; CI,1.0005-1.0046; P=0.012). No significant associations between functional connectivity of the resting-state networks and depressive disorders were found in this MR study.
CONCLUSIONS
These results suggest that genetically determined structural connectivity of the limbic network has a causal effect on depressive disorders and may play a critical role in its neuropathology.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Magnetic Resonance Imaging; Nerve Net; Depressive Disorder; Brain; Female; Connectome; Male
PubMed: 38811927
DOI: 10.1186/s12888-024-05857-2 -
BMC Psychiatry May 2024Motor alterations and lowered physical activity are common in affective disorders. Previous research has indicated a link between depressive symptoms and declining... (Observational Study)
Observational Study
The association between maximal muscle strength, disease severity and psychopharmacotherapy among young to middle-aged inpatients with affective disorders - a prospective pilot study.
BACKGROUND
Motor alterations and lowered physical activity are common in affective disorders. Previous research has indicated a link between depressive symptoms and declining muscle strength primarily focusing on the elderly but not younger individuals. Thus, we aimed to evaluate the relationship between mood and muscle strength in a sample of N = 73 young to middle-aged hospitalized patients (18-49 years, mean age 30.7 years) diagnosed with major depressive, bipolar and schizoaffective disorder, with a focus on moderating effects of psychopharmacotherapy. The study was carried out as a prospective observational study at a German psychiatric university hospital between September 2021 and March 2022.
METHODS
Employing a standardized strength circuit consisting of computerized strength training devices, we measured the maximal muscle strength (F) using three repetitions maximum across four muscle regions (abdomen, arm, back, leg) at three time points (t-t) over four weeks accompanied by psychometric testing (MADRS, BPRS, YRMS) and blood lipid profiling in a clinical setting. For analysis of psychopharmacotherapy, medication was split into activating (AM) and inhibiting (IM) medication and dosages were normalized by the respective WHO defined daily dose.
RESULTS
While we observed a significant decrease of the MADRS score and increase of the relative total F (rTF) in the first two weeks (t-t) but not later (both p < .001), we did not reveal a significant bivariate correlation between disease severity (MADRS) and muscle strength (rTF) at any of the timepoints. Individuals with longer disease history displayed reduced rTF (p = .048). IM was significantly associated with decreased rTF (p = .032). Regression models provide a more substantial effect of gender, age, and IM on muscle strength than the depressive episode itself (p < .001).
CONCLUSIONS
The results of the study indicate that disease severity and muscle strength are not associated in young to middle-aged inpatients with affective disorders using a strength circuit as observational measurement. Future research will be needed to differentiate the effect of medication, gender, and age on muscle strength and to develop interventions for prevention of muscle weakness, especially in younger patients with chronic affective illnesses.
Topics: Humans; Muscle Strength; Male; Pilot Projects; Adult; Female; Prospective Studies; Middle Aged; Young Adult; Adolescent; Inpatients; Bipolar Disorder; Depressive Disorder, Major; Psychotic Disorders; Severity of Illness Index
PubMed: 38811916
DOI: 10.1186/s12888-024-05849-2 -
Scientific Reports May 2024Depression has been reported as one of the most prevalent psychiatric illnesses globally. This study aimed to obtain information on the global burden of depression and...
Depression has been reported as one of the most prevalent psychiatric illnesses globally. This study aimed to obtain information on the global burden of depression and its associated spatiotemporal variation, by exploring the correlation between the global burden of depression and the social development index (SDI) and associated risk factors. Using data from the Global Burden of Disease study from 1990 to 2019, we described the prevalence and burden of disease in 204 countries across 21 regions, including sex and age differences and the relationship between the global disease burden and SDI. The age-standardized rate and estimated annual percentage change were used to assess the global burden of depression. Individuals with documented depression globally ranged from 182,183,358 in 1990 to 290,185,742 in 2019, representing an increase of 0.59%. More patients experienced major depressive disorder than dysthymia. The incidence and disability-adjusted life years of depression were the highest in the 60-64 age group and much higher in females than in males, with this trend occurring across all ages. The age-standardized incidence and adjusted life-years-disability rates varied with different SDI levels. Relevant risk factors for depression were identified. National governments must support research to improve prevention and treatment interventions.
Topics: Humans; Global Burden of Disease; Male; Female; Middle Aged; Adult; Aged; Risk Factors; Depression; Prevalence; Adolescent; Young Adult; Incidence; Global Health; Depressive Disorder, Major; Cost of Illness; Disability-Adjusted Life Years; Spatio-Temporal Analysis; Child
PubMed: 38811645
DOI: 10.1038/s41598-024-62381-9 -
Translational Psychiatry May 2024Testosterone has complex effects on psychological traits and behavior; it is associated with social dominance and competition and is a potential human sex pheromone....
Testosterone has complex effects on psychological traits and behavior; it is associated with social dominance and competition and is a potential human sex pheromone. This study aimed to investigate the associations between testosterone levels, aggressive behavior, and manic symptoms using a network analysis among bipolar disorder (BD) patients in psychiatric emergency departments (PED). Data from January 2021 and March 2022 BD patients in PED were analyzed. Manic symptoms were assessed using the Young Mania Rating Scale (YMRS). Aggression was assessed with subscale of the PANSS scale (PANSS-AG). The undirected network structures of testosterone levels, aggressive behavior, and manic symptoms were estimated, and centrality and bridge centrality indices were examined. Network stability was examined using the case-dropping procedure. The Network Comparison Test (NCT) was conducted to evaluate whether network characteristics differed by gender. We recruited a total of 898 BD patients, with the mean YMRS score as 13.30 ± 9.58. The prevalence of level II aggression was 35.6% (95%CI = 32.5%-38.7%), level III aggression was 29.5% (95%CI = 26.3%-32.6%), and level VI aggression was 7.0% (95%CI = 5.4%-8.8%). The male participants had a mean testosterone level of 391.71 (Standard Deviation (SD):223.39) compared to 36.90 (SD:30.50) for female participants in the whole sample. Through network analysis, "Increased motor activity-energy" emerged as the central symptom, with the highest centrality expected influence, followed by "Emotional Instability" and "Disruptive/aggression behavior". Notably, "Emotional Instability" appeared to be the bridge symptom linking manic symptoms to aggressive behavior. Within the flow network model, "Speech rate and amount" exhibited the strongest positive correlation with testosterone levels, followed closely by "Disruptive/aggression behavior". The constructed network model demonstrated robust stability, with gender showing no significant impact on the structure. In this study, "Increased motor activity-energy" stood out as the most influential symptom, and "Speech rate and amount" acted as the main bridge symptom linking testosterone levels, aggressive behavior, and manic symptoms. Targeting the central and bridge symptoms may improve the outcomes of aggression interventions implemented among BD patients in psychiatric emergency care.
Topics: Humans; Bipolar Disorder; Aggression; Testosterone; Male; Female; Adult; Cross-Sectional Studies; Middle Aged; Comorbidity; Mania; Psychiatric Status Rating Scales; Young Adult
PubMed: 38811572
DOI: 10.1038/s41398-024-02957-1 -
Translational Psychiatry May 2024Omega-3 fatty acids have been implicated in the aetiology of depressive disorders, though trials supplementing omega-3 to prevent major depressive disorder (MDD) have so...
Omega-3 fatty acids have been implicated in the aetiology of depressive disorders, though trials supplementing omega-3 to prevent major depressive disorder (MDD) have so far been unsuccessful. Whether this association is causal remains unclear. We used two sample Mendelian randomization (MR) to investigate causality. Genetic variants associated with circulating omega-3 and omega-6 fatty acids in UK Biobank (UKBB, n = 115,078) were selected as exposures. The Psychiatric Genomics Consortium (PGC) genome-wide association studies (GWAS) of MDD (n = 430,775; cases = 116,209; controls = 314,566) and recurrent depression (rMDD, n = 80,933; cases = 17,451; controls = 62,482), were used as outcomes. Multivariable MR (MVMR) models were used to account for biologically correlated lipids, such as high- and low-density cholesterol and triglycerides, and to explore the relative importance of longer-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) using data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE, n = 8866). Genetic colocalization analyses were used to explore the presence of a shared underlying causal variant between traits. Genetically predicted total omega-3 fatty acids reduced the odds of MDD (OR 0.96 per standard deviation (SD, i.e. 0.22 mmol/l) (95% CIs 0.93-0.98, p = 0.003)). The largest point estimates were observed for eicosapentaenoic acid (EPA), a long-chain omega-3 fatty acid (OR 0.92; 95% CI 0.88-0.96; p = 0.0002). The effect of omega-3 fatty acids was robust to MVMR models accounting for biologically correlated lipids. 'Leave-one-out' analyses highlighted the FADS gene cluster as a key driver of the effect. Colocalization analyses suggested a shared causal variant using the primary outcome sample, but genomic confounding could not be fully excluded. This study supports a role for omega-3 fatty acids, particularly EPA, in the aetiology of depression, although pleiotropic mechanisms cannot be ruled out. The findings support guidelines highlighting the importance of EPA dose and ratio for MDD and question whether targeted interventions may be superior to universal prevention trials, as modest effect sizes will limit statistical power.
Topics: Humans; Mendelian Randomization Analysis; Depressive Disorder, Major; Fatty Acids, Omega-3; Genome-Wide Association Study; Female; Male; Polymorphism, Single Nucleotide; Middle Aged; Eicosapentaenoic Acid; Docosahexaenoic Acids; Delta-5 Fatty Acid Desaturase; Fatty Acid Desaturases; Adult; Fatty Acids, Omega-6; Aged; United Kingdom
PubMed: 38811538
DOI: 10.1038/s41398-024-02932-w -
PloS One 2024To determine whether a bidirectional causal relationship exists between major depressive disorder (MDD) and heart failure (HF).
OBJECTIVE
To determine whether a bidirectional causal relationship exists between major depressive disorder (MDD) and heart failure (HF).
METHODS
Our two-sample bidirectional Mendelian randomization (MR) study consisted of two parts. In the first part, we conducted a forward MR analysis where MDD was considered as the exposure and HF as the outcome. In the second part, a reverse MR analysis was performed, treating HF as the exposure and MDD as the outcome. Summary data on MDD and HF were obtained from the IEU Open GWAS database.
RESULTS
Based on the results of the MR-Egger regression intercept test, there was no evidence of horizontal pleiotropy in this study. Furthermore, the IVW results consistently suggested estimates of causal effect values. The findings revealed that individuals with MDD had a 16.9% increased risk of HF compared to those without MDD (OR = 1.169, 95%CI: 1.044-1.308, P = 0.007). However, there was no evidence to support that HF would increase the risk of MDD (OR = 1.012, 95%CI: 0.932-1.099, P = 0.773). Heterogeneity in SNPs of MDD and HF was observed through the heterogeneity test and funnel plot. Additionally, the leave-one-out method did not identify any instances where a single SNP was biased toward or dependent on causation.
CONCLUSION
Our study provides evidence supporting a one-way causal relationship between MDD and HF. Specifically, MDD increases the risk of developing HF. However, our findings did not provide any evidence suggesting that HF increases the risk of developing MDD.
Topics: Humans; Depressive Disorder, Major; Heart Failure; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Genetic Predisposition to Disease; Risk Factors
PubMed: 38809848
DOI: 10.1371/journal.pone.0304379