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Nature. Mental Health 2024Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical...
Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples ( = 1,384) of medication-free individuals with first-episode and recurrent MDD ( = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls ( = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals ( = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter ( = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter ( = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) ( = -18.3, 95% CI (-34.3 to -2.3), = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.
PubMed: 38948238
DOI: 10.1038/s44220-023-00187-w -
Theranostics 2024: Recent evidence highlights the pivotal role of mitochondrial dysfunction in mood disorders, but the mechanism involved remains unclear. We studied whether the...
: Recent evidence highlights the pivotal role of mitochondrial dysfunction in mood disorders, but the mechanism involved remains unclear. We studied whether the Hippo/YAP/14-3-3η signaling pathway mediates mitochondrial abnormalities that result in the onset of major depressive disorder (MDD) in a mouse model. : The ROC algorithm was used to identify a subpopulation of mice that were exposed to chronic unpredictable mild stress (CUMS) and exhibited the most prominent depressive phenotype (Dep). Electron microscopy, biochemical assays, quantitative PCR, and immunoblotting were used to evaluate synaptic and mitochondrial changes in the basolateral amygdala (BLA). RNA sequencing was used to explore changes in the Hippo pathway and downstream target genes. pharmacological inhibition and immunoprecipitation was used to confirm YAP/14-3-3η interaction and its role in neuronal mitochondrial dysfunction. We used virus-mediated gene overexpression and knockout in YAP transgenic mice to verify the regulatory effect of the Hippo/YAP/14-3-3η pathway on depressive-like behavior. : Transcriptomic data identified a large number of genes and signaling pathways that were specifically altered from the BLA of Dep mice. Dep mice showed notable synaptic impairment in BLA neurons, as well as mitochondrial damage characterized by abnormal mitochondrial morphology, compromised function, impaired biogenesis, and alterations in mitochondrial marker proteins. The Hippo signaling pathway was activated in Dep mice during CUMS, and the transcriptional regulatory activity of YAP was suppressed by phosphorylation of its Ser127 site. 14-3-3η was identified as an important co-regulatory factor of the Hippo/YAP pathway, as it can respond to chronic stress and regulate cytoplasmic retention of YAP. Importantly, the integrated Hippo/YAP/14-3-3η pathway mediated neuronal mitochondrial dysfunction and depressive behavior in Dep mice. : The integrated Hippo/YAP/14-3-3η pathway in the BLA neuron is critical in mediating depressive-like behaviors in mice, suggesting a causal role for this pathway in susceptibility to chronic stress-induced depression. This pathway therefore may present a therapeutic target against mitochondrial dysfunction and synaptic impairment in MDD.
Topics: Animals; Disease Models, Animal; Mice; Mitochondria; YAP-Signaling Proteins; Signal Transduction; Hippo Signaling Pathway; Basolateral Nuclear Complex; Protein Serine-Threonine Kinases; Male; Stress, Psychological; 14-3-3 Proteins; Adaptor Proteins, Signal Transducing; Depressive Disorder, Major; Depression; Mice, Inbred C57BL; Neurons; Mice, Transgenic
PubMed: 38948066
DOI: 10.7150/thno.92676 -
Frontiers in Public Health 2024Postpartum fatigue (PPF) can impair the physical and mental well-being of women. The aims of this study were to assess the associations between fatigue and maternal...
BACKGROUND
Postpartum fatigue (PPF) can impair the physical and mental well-being of women. The aims of this study were to assess the associations between fatigue and maternal health-related variables, specifically, sleep quality, depression symptoms, and resilience, and to explore the moderating role of resilience in the relationships between sleep quality, depression symptoms, and fatigue.
METHODS
This cross-sectional study used data collected from mothers during the postpartum period via an online platform. PPF was assessed using the Fatigue Severity Scale, whereas sleep quality and depression symptoms were assessed using the Pittsburgh Sleep Quality Index and Edinburgh Postnatal Depression Scale, respectively. The Brief Resilience Scale was used to assess resilience. Simple and multiple binary logistic regression analyses were performed to examine the association of each independent variable with PPF and to determine the most significant predictors of PFF. The data were analyzed using SPSS, and structural equation modeling was performed using AMOS 23. A moderation analysis was performed to explore the moderating role of resilience using the Hayes PROCESS macro.
RESULTS
A total of 1,443 postpartum mothers were included in the analysis. The simple binary logistic regression analysis showed that having chronic disease (odds: 1.52; = 0.02), mother's age (odds: 0.97; = 0.03), mother's body mass index (BMI; odds: 1.03; = 0.01), depression symptoms (odds: 1.09; ≤ 0.0001), sleep quality (odds: 1.17; ≤ 0.0001), and resilience (odds: 0.42; p ≤ 0.0001) all contributed to fatigue during postpartum. Multivariate logistic regression showed that the mother's BMI, sleep quality, depression symptoms, and resilience were significant predictors of PPF. Moderation analyses showed that resilience was not a significant moderator between the main effects of sleep quality and fatigue (interaction effect: = 0.01, = 0.31, 95% CI: -0.01 to 0.04) or between the main effects of depression symptoms and fatigue during postpartum (interaction effect: = 0.01, = 0.82, 95% CI: -0.01 to 0.02).
CONCLUSION
Given the deleterious effects of PPF on maternal health outcomes, factors associated with PPF should be assessed regularly. In addition to mothers' BMI, sleep quality, and depression symptoms, resilience could also be a crucial factor in predicting fatigue severity during this critical time for mothers even though it was not a significant moderator among this sample.
Topics: Humans; Female; Cross-Sectional Studies; Adult; Fatigue; Resilience, Psychological; Postpartum Period; Mothers; Sleep Quality; Surveys and Questionnaires; Depression, Postpartum; Depression; Risk Factors; Logistic Models
PubMed: 38947349
DOI: 10.3389/fpubh.2024.1394380 -
MedRxiv : the Preprint Server For... Jun 2024Cannabis is one of the most widely used drugs globally. Decriminalization of cannabis is further increasing cannabis consumption. We performed genome-wide association...
Cannabis is one of the most widely used drugs globally. Decriminalization of cannabis is further increasing cannabis consumption. We performed genome-wide association studies ( ) of lifetime ( 131,895) and frequency ( 73,374) of cannabis use. Lifetime cannabis use GWAS identified two loci, one near (rs11922956, =2.40E-11) and another near (rs12673181, =6.90E-09). Frequency of use GWAS identified one locus near (rs4856591, =8.10E-09; =0.76 with rs11922956). Both traits were heritable and genetically correlated with previous GWASs of lifetime use and cannabis use disorder ( ), as well as other substance use and cognitive traits. Polygenic scores ( ) for lifetime and frequency of cannabis use associated cannabis use phenotypes in participants. Phenome-wide association study of lifetime cannabis use PGS in a hospital cohort replicated associations with substance use and mood disorders, and uncovered associations with celiac and infectious diseases. This work demonstrates the value of GWASs of CUD transition risk factors.
PubMed: 38947071
DOI: 10.1101/2024.06.14.24308946 -
MedRxiv : the Preprint Server For... Jun 2024Impulsivity can be a risk factor for serious complications for those with mood disorders. To understand intra-individual impulsivity variability, we analyzed...
Impulsivity can be a risk factor for serious complications for those with mood disorders. To understand intra-individual impulsivity variability, we analyzed longitudinal data of a novel gamified digital Go/No-Go (GNG) task in a clinical sample (n=43 mood disorder participants, n=17 healthy controls) and an open-science sample (n=121, self-reported diagnoses). With repeated measurements within-subject, we disentangled two aspects of GNG: reaction time and accuracy in response inhibition (i.e., incorrect No-Go trials) with respect to diurnal and potential learning effects. Mixed-effects models showed diurnal effects in reaction time but not accuracy, with a significant effect of hour on reaction time in the clinical sample and the open-science sample. Moreover, subjects improved on their response inhibition but not reaction time. Additionally, significant interactions emerged between depression symptom severity and time-of-day in both samples, supporting that repeated administration of our GNG task can yield mood-dependent circadian rhythm-aware biomarkers of neurocognitive function.
PubMed: 38947017
DOI: 10.1101/2024.06.12.24308834 -
MedRxiv : the Preprint Server For... Jun 2024Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative....
IMPORTANCE
Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative. Distributed white matter (WM) impairments in individuals with heroin use disorder (iHUD) have been associated with increased drug craving, a reliable predictor of treatment outcomes. However, little is known about the extent of whole-brain structural connectivity changes with inpatient treatment and abstinence in iHUD.
OBJECTIVE
To assess WM microstructure and associations with drug craving changes with inpatient treatment in iHUD (effects of time/re-scan compared to controls; CTL).
DESIGN
Longitudinal cohort study (12/2020-09/2022) where iHUD and CTL underwent baseline magnetic resonance imaging (MRI#1) and follow-up (MRI#2) scans, (mean interval of 13.9 weeks in all participants combined).
SETTING
The iHUD and CTL were recruited from urban inpatient treatment facilities and surrounding communities, respectively.
PARTICIPANTS
Thirty-four iHUD (42.1yo; 7 women), 25 age-/sex-matched CTL (40.5yo; 9 women).
INTERVENTION
Between scans, inpatient iHUD continued their medically-assisted treatment and related clinical interventions. CTL participants were scanned at similar time intervals.
MAIN OUTCOMES AND MEASURES
Changes in white matter diffusion metrics [fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivities (RD)] in addition to baseline and cue-induced drug craving, and other clinical outcome variables (mood, sleep, affect, perceived stress, and therapy attendance).
RESULTS
Main findings showed HUD-specific WM microstructure changes encompassing mostly frontal major callosal, projection, and association tracts, characterized by increased FA (.949<1- p<.986) and decreased MD (.949<1-p<.997) and RD (.949<1-p<.999). The increased FA (r=- 0.72, p<.00001) and decreased MD (r=0.69, p<.00001) and RD (r=0.67, p<.0001) in the genu and body of the corpus callosum and the left anterior corona radiata in iHUD were correlated with a reduction in baseline craving (.949<1-p<.999). No other WM correlations with outcome variables reached significance.
CONCLUSIONS AND RELEVANCE
Our findings suggest whole-brain normalization of structural connectivity with inpatient medically-assisted treatment in iHUD encompassing recovery in frontal WM pathways implicated in emotional regulation and top-down executive control. The association with decreases in baseline craving further supports the relevance of these WM markers to a major symptom in drug addiction, with implications for monitoring clinical outcomes.
KEY POINTS
Does white matter (WM) microstructure change with medication-assisted treatment in individuals with heroin use disorder (iHUD)? In this longitudinal cohort study, diffusion MRI was acquired in 34 inpatient iHUD and 25 healthy controls (CTL) twice, separated by a mean of 13.9 weeks. We found HUD- specific WM microstructure changes with time, characterized by increased anisotropy and decreased diffusivity in fronto-striatal WM pathways. These changes were correlated with decreased baseline drug craving with treatment. Frontal WM changes and associated drug craving decreases suggest brain-behavior recovery with inpatient treatment in iHUD, potentially contributing to reduced drug use and sustained abstinence.
PubMed: 38946983
DOI: 10.1101/2024.06.10.24308719 -
Physiology & Behavior Jun 2024The roles of metabolic signals, including Glucagon-like peptide 1 (GLP-1), have been implicated in multiple domains outside metabolic regulation. There is a growing... (Review)
Review
INTRODUCTION
The roles of metabolic signals, including Glucagon-like peptide 1 (GLP-1), have been implicated in multiple domains outside metabolic regulation. There is a growing interest in repurposing Glucagon-like peptide 1 receptor agonists (GLP-1RAs) as therapeutics for motivation and reward-related behavioural disturbances. Herein, we aim to systematically review the extant evidence on the potential effects of GLP-1RAs on the reward system.
METHODS
The study followed PRISMA guidelines using databases such as OVID, PubMed, Scopus, and Google Scholar. The search focused on "Reward Behavior" and "Glucagon Like Peptide 1 Receptor Agonists" and was restricted to human studies. Quality assessment achieved by the NIH's Quality Assessment of Controlled Intervention Studies RESULTS: GLP-1RAs consistently reduced energy intake and influenced reward-related behaviour. These agents have been associated with decreased neurocortical activation in response to higher rewards and food cues, particularly high-calorie foods, and lowered caloric intake and hunger levels.
DISCUSSION
GLP-1RAs show promise in addressing reward dysfunction linked to food stimuli, obesity, and T2DM. They normalize insulin resistance, and might also modulate dopaminergic signalling and reduce anhedonia. Their effects on glycemic variability and cravings suggest potential applications in addiction disorders.
PubMed: 38945189
DOI: 10.1016/j.physbeh.2024.114622 -
Brain Research Jun 2024Oxidative stress plays a pivotal role in various neurological disorders, encompassing both neurodegenerative diseases such as Alzheimer's and Parkinson's, and mood...
Oxidative stress plays a pivotal role in various neurological disorders, encompassing both neurodegenerative diseases such as Alzheimer's and Parkinson's, and mood disorders like depression. The balance between the generation of reactive oxygen species (ROS) and the cell's antioxidant defenses, when disrupted, can lead to neuronal damage and neurologic dysfunction. In this study, we focused on the pathogenic role of oxidative stress in various neurologic disease models in vitro and investigated the neuroprotective capabilities of some novel bicyclic γ-butyrolactone compounds, with particular emphasis on the compound designated as 'bd'. Our investigation leveraged the HT22 and SH-SY5Y cells to model oxidative stress induced by HO or corticosterone (CORT), common triggers of neuronal damage in neurodegenerative and mood disorders. We discovered that compound bd robustly reduced ROS production and suppressed neuronal apoptosis, suggesting its potential in treating a wider array of neurological conditions influenced by oxidative stress. In conclusion, our research underscores the importance of addressing oxidative stress in the context of diverse neurological disorders. The identification of compound bd as a neuroprotective agent with potential efficacy against ROS-induced apoptosis in neural cells opens new horizons for therapeutic development, offering hope for patients suffering from neurodegenerative diseases, depression, and other stress-related neurological conditions.
PubMed: 38942352
DOI: 10.1016/j.brainres.2024.149099 -
Medicine Jun 2024Observational studies have reported a relationship between multiple common dermatoses and mental illness. To assess the potential bidirectional causality between 3 skin...
Observational studies have reported a relationship between multiple common dermatoses and mental illness. To assess the potential bidirectional causality between 3 skin disorders (psoriasis, eczema, and urticaria) and 4 psychiatric disorders (bipolar disorder, schizophrenia, major depressive disorder, and anxiety) in the European population, we used Mendelian randomization (MR) analysis, which provides definitive evidence for causal inference. Eligible single nucleotide polymorphisms were screened for dermatological and psychiatric disorders using a genome-wide association study database. We conducted bidirectional, 2-sample MR analysis using instrumental variables related to psoriasis, eczema, and urticaria as exposure factors, and bipolar disorder, schizophrenia, major depression, and anxiety as outcomes. Reverse MR analysis with bipolar disorder, schizophrenia, major depression, and anxiety as exposure and psoriasis, eczema, and urticaria as outcomes were also performed, and the causality was analyzed using inverse-variance weighting (IVW), MR-Egger, and weighted median methods. To thoroughly assess causality, sensitivity analyses were conducted using the IVW, MR-PRESSO, and MR-Egger methods. The results showed that bipolar disorder increased the incidence of psoriasis (odds ratio = 1.271, 95% confidence interval = 1.003-1.612, P = .047), heterogeneity test with Cochran Q test in the IVW showed P value > .05, (P = .302), the MR-Pleiotropy and MR-PRESSO (outlier methods) in the multiplicity test showed P value > .05, (P = .694; P = .441), and MR-Pleiotropy evidence showed no apparent intercept (intercept = -0.060; SE = 0.139; P = .694). Major depression increased the risk of eczema (odds ratio = 1.002, 95% confidence interval = 1.000-1.004, P = .024), heterogeneity test showed P value > .05, (P = .328), multiplicity detection showed P value > .05, (P = .572; P = .340), and MR-Pleiotropy evidence showed no apparent intercept (intercept = -0.099; SE = 0.162; P = .572). Sensitivity analyses of the above results were reliable, and no heterogeneity or multiplicity was found. This study demonstrated a statistically significant causality between bipolar disorder and psoriasis, major depression, and eczema in a European population, which could provide important information for physicians in the clinical management of common skin conditions.
Topics: Humans; Mendelian Randomization Analysis; Psoriasis; Eczema; Europe; Polymorphism, Single Nucleotide; Urticaria; Mental Disorders; Genome-Wide Association Study; Bipolar Disorder; Female; Schizophrenia; Depressive Disorder, Major; Causality; Male
PubMed: 38941419
DOI: 10.1097/MD.0000000000038586 -
MAJOR DEPRESSIVE DISORDERS IN PAEDIATRIC SURGICAL PATIENTS: AN OVERVIEW OF THE NIGERIAN ADOLESCENTS.Annals of Ibadan Postgraduate Medicine Apr 2024Less than three decades ago, depression was seen as a predominantly adult disorder as children were considered too developmentally immature to experience depressive...
INTRODUCTION
Less than three decades ago, depression was seen as a predominantly adult disorder as children were considered too developmentally immature to experience depressive disorders, and adolescent low mood was considered as part of 'normal' teenage mood swings. Major depressive disorder in children and adolescents is a serious psychiatric illness especially in paediatric surgical patients. This may be due to their altered metabolic rate and heighten metabolic response to trauma which has significant implications for the psychological development of the child, yet it remains under-recognized and undertreated. The well-being of the care givers is also not left out as the care givers are inundated with the task of sourcing and providing finance for hospital care., in addition to the stress of providing care for the patient. This may result in loss of man hour, sleeplessness, and physical exhaustion associated with caring for these ill children which can ultimately significantly increase the risk of them having depressive episode. The aim of this commentary is to highlight the fact that paediatric surgical patients are not exempt to having a major depressive disorder and the care givers should also be evaluated during hospital admission of their wards.
METHODOLOGY
This is a commentary on depressive disorders among Nigerian paediatric surgical patients. Related publications on children and adolescents presenting to hospital were searched using the domain - Depression in Nigerian adolescent, Paediatric surgery patients on PubMed, Google Scholar, and MEDLINE to appraise this review.
CONCLUSION
Mood disorders, especially depression in children and adolescents have been studied increasingly over the last two decades and surgical conditions worsen the outlook, culminating in increased knowledge about the presentation, and treatment. Despite this, it is still often missed or misdiagnosed because it sometimes presents with uncharacteristic symptoms. Prevalence of depressiion among paediatric surgical patient were found to be between 46-82% in this review among Nigerian patients.
PubMed: 38939881
DOI: No ID Found