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PloS One 2024Skin neglected tropical diseases including leprosy and Buruli ulcer (BU)are a group of stigmatizing and disability-inducing conditions and these aspects of the diseases...
BACKGROUND
Skin neglected tropical diseases including leprosy and Buruli ulcer (BU)are a group of stigmatizing and disability-inducing conditions and these aspects of the diseases could lead to poor mental health. The study was designed to assess the burden of poor mental health and wellbeing among persons affected by leprosy or BU in Nigeria.
METHODS
A community based cross-sectional study design was employed. The study involved persons affected by leprosy or BU. Ten local government areas with the highest number of notified leprosy or BU cases between 2014 and 2018 in southern Nigeria were purposively selected. Information were obtained using Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorders-7 (GAD-7), Warwick-Edinburgh Mental Well-being Scale (WEMWBS) and OSLO Social Support Scale. Outcome measure was poor mental health/wellbeing and was determined by proportion of respondents who had depressive symptoms, anxiety disorder and poor mental wellbeing.
RESULTS
A total of 635 persons affected by leprosy or BU participated in the study. The mean age of respondents was 43.8±17.0 years and highest proportion, 22.2% were in age group, 40-49 years. Majority of respondents, 50.7% were males. A higher proportion of respondents, 89.9% had depressive symptoms, 79.4% had anxiety disorders and 66.1% had poor mental wellbeing. Majority, 57.2% had poor mental health/wellbeing. Among the respondents, there was a strong positive correlation between depression and anxiety scores, (r = 0.772, p<0.001). There was a weak negative correlation between depression score and WEMWBS score, (r = -0.457, p<0.001); anxiety score and WEMWBS score, (r = -0.483, p<0.001). Predictors of poor mental health/wellbeing included having no formal education, (AOR = 1.9, 95%CI: 1.1-3.3), being unemployed, (AOR = 3.4, 95%CI: 2.2-5.3), being affected by leprosy, (AOR = 0.2, 95%CI: 0.1-0.4) and having poor social support, (AOR = 6.6, 95%CI: 3.7-11.8).
CONCLUSIONS
The burden of poor mental health/wellbeing among persons affected by leprosy or BU is very high. There is need to include mental health interventions in the management of persons affected with leprosy or BU. Equally important is finding a feasible, cost-effective and sustainable approach to delivering mental health care for persons affected with leprosy or BU at the community level. Improving educational status and social support of persons affected by leprosy or BU are essential. Engaging them in productive activities will be of essence.
Topics: Humans; Leprosy; Male; Nigeria; Female; Buruli Ulcer; Adult; Cross-Sectional Studies; Middle Aged; Mental Health; Depression; Young Adult; Adolescent; Aged; Social Support; Surveys and Questionnaires
PubMed: 38885248
DOI: 10.1371/journal.pone.0304786 -
Frontiers in Medicine 2024The association between depression and musculoskeletal diseases has long been a subject of contentious debate. However, the causal relationship between the two remains...
BACKGROUND
The association between depression and musculoskeletal diseases has long been a subject of contentious debate. However, the causal relationship between the two remains uncertain. This study employs a two-sample Mendelian randomization (MR) analysis to investigate the causality between depression and six musculoskeletal diseases.
METHODS
In this study, we performed MR analysis to systematically explore the causal relationship between depression and six musculoskeletal disorders. Single nucleotide polymorphisms (SNPs) that are linked to depression were employed as instrumental variables. To ensure robust and reliable conclusions, multiple analytical approaches were utilized, including inverse variance weighting(IVW), weighted median, and MR-Egger regression. Additionally, sensitivity analysis methods such as the MR-Egger intercept test, Cochran's Q test, leave-one-out analysis, and funnel plot were employed.
RESULTS
Our MR analysis revealed a significant association between depression and cervical spondylosis (depression: OR 1.003, 95% CI 1.002-1.005, = 8.32E-05; major depressive disorder: OR 1.003, 95% CI 1.001-1.005, = 0.0052). Furthermore, a strong correlation was noted between major depressive disorder (MDD) and knee osteoarthritis (KOA) (OR 1.299, 95% CI 1.154-1.463, = 1.50E-5). Sensitivity analysis confirmed the robustness of these findings. Our independent validation study also corroborated these results.
CONCLUSION
The MR analysis conducted in this study provides evidence supporting a genetic link between depression and cervical spondylosis, as well as KOA. Targeted interventions to manage depression in susceptible populations may contribute to lowering the risk of cervical spondylosis and KOA in these cohorts.
PubMed: 38882662
DOI: 10.3389/fmed.2024.1398203 -
Frontiers in Genetics 2024An association between depression and migraine has been reported in observational studies; however, conventional observational studies are prone to bias. This study aims...
BACKGROUND
An association between depression and migraine has been reported in observational studies; however, conventional observational studies are prone to bias. This study aims to investigate the causal relationship between depression and migraine and to quantify the mediating effects of known risk factors.
METHODS
We applied two-sample Mendelian randomization and utilized single nucleotide polymorphisms as genetic instruments for exposure (depression) and mediators (sleep traits). We utilized summary data on genome-wide association studies for depression, sleep-related traits mediators and migraine. For depression, genome-wide association studies (depression) were utilized as a test cohort for the primary analysis. Moreover, genome-wide association studies (major depressive disorder) were utilized to test the stability of the results for the validation cohort. IVW and MR-Egger regression were applied to test the heterogeneity, and Cochran's Q statistics were calculated to quantitatively evaluate the heterogeneity. MR-PRESSO analyses were utilized to examine and correct possible horizontal pleiotropy through removing outliers, and leave-one-out analyses were utilized to identify outlier SNPs.
RESULTS
Genetically predicted depression was associated with migraine (OR = 1.321, 95% CI: 1.184-1.473, < 0.001). Furthermore, risk factors insomnia was associated with migraine risk (OR = 1.766, 95% CI: 1.120-2.784, = 0.014). The mediator insomnia accounted for 19.5% of the total effect of depression on migraine.
CONCLUSION
These results support a potential causal effect of depression on migraine, partly mediated by insomnia. Therefore, the enhancement of sleep quality and difficulty in falling asleep may reduce the migraine burden occasioned by depression.
PubMed: 38881795
DOI: 10.3389/fgene.2024.1326817 -
Frontiers in Psychiatry 2024Emerging evidence links cellular senescence to the pathogenesis of major depressive disorder (MDD), a life-threatening and debilitating mental illness. However, the...
BACKGROUND
Emerging evidence links cellular senescence to the pathogenesis of major depressive disorder (MDD), a life-threatening and debilitating mental illness. However, the roles of cellular senescence-related genes in MDD are largely unknown and were investigated in this study using a comprehensive analysis.
METHODS
Peripheral blood microarray sequencing data were downloaded from Gene Expression Omnibus (GEO) database and retrieved cellular senescence-related genes from CellAge database. A weighted gene co-expression network analysis was used to screen MDD-associated genes. Protein-protein interactions (PPI) were predicted based on STRING data, and four topological algorithms were used to identify hub genes from the PPI network. Immune infiltration was evaluated using CIBERSORT, followed by a correlation analysis between hub genes and immune cells.
RESULTS
A total of 84 cell senescence-related genes were differentially expressed in patients with MDD compared to healthy control participants. Among the 84 genes, 20 were identified to be associated with the MDD disease phenotype, and these genes were mainly involved in hormone-related signaling pathways (such as estrogen, steroid hormone, and corticosteroid) and immune and inflammatory pathways. Three genes, namely, JUN, CTSD, and CALR, which were downregulated in MDD, were identified as the hub genes. The expression of hub genes significantly moderate correlated with multiple immune cells, such as Tregs, NK cells, and CD4+ T cells, and the abundance of these immune cells markedly differed in MDD samples. Multiple microRNAs, transcription factors, and small-molecule drugs targeting hub genes were predicted to explore their molecular regulatory mechanisms and potential therapeutic value in MDD.
CONCLUSION
JUN, CTSD, and CALR were identified as potential diagnostic markers of MDD and may be involved in the immunoinflammatory mechanism of MDD.
PubMed: 38881549
DOI: 10.3389/fpsyt.2024.1372386 -
Biological & Pharmaceutical Bulletin 2024The increasing number of patients with depressive disorder is a serious socioeconomic problem worldwide. Although several therapeutic agents have been developed and used...
The increasing number of patients with depressive disorder is a serious socioeconomic problem worldwide. Although several therapeutic agents have been developed and used clinically, their effectiveness is insufficient and thus discovery of novel therapeutic targets is desired. Here, focusing on dysregulation of neuronal purinergic signaling in depressive-like behavior, we examined the expression profiles of ATP channels and ectonucleotidases in astrocytes of cerebral cortex and hippocampus of chronic social defeat stress (CSDS)-susceptible BALB/c mice. Mice were exposed to 10-d CSDS, and their astrocytes were obtained using a commercially available kit based on magnetic activated cell sorting technology. In astrocytes derived from cerebral cortex of CSDS-susceptible mice, the expression levels of mRNAs for connexin 43, P2X7 receptors and maxi anion channels were increased, those for connexin 43 and P2X7 receptors being inversely correlated with mouse sociability, and the expression of mRNAs for ecto-nucleoside triphosphate diphosphohydrase 2 and ecto-5'nucleotidase was decreased and increased, respectively. On the other hand, the alteration profiles of ATP channels and ectonucleotidases in hippocampal astrocytes of CSDS-susceptible mice were different from in the case of cortical astrocytes, and there was no significant correlation between expression levels of their mRNAs and mouse sociability. These findings imply that increased expression of ATP channels in cerebral cortex might be involved in the development of reduced sociability in CSDS-subjected BALB/c mice. Together with recent findings, it is suggested that ATP channels expressed by cortical astrocytes might be potential therapeutic targets for depressive disorder.
Topics: Animals; Astrocytes; Cerebral Cortex; Hippocampus; Mice, Inbred BALB C; Stress, Psychological; Male; Social Defeat; Mice; Receptors, Purinergic P2X7; Connexin 43; 5'-Nucleotidase; Adenosine Triphosphatases; RNA, Messenger
PubMed: 38880625
DOI: 10.1248/bpb.b24-00236 -
Brain Stimulation Jun 2024The effect of transcranial alternating current stimulation (tACS) on major depressive disorder (MDD) was not confirmed.
BACKGROUND
The effect of transcranial alternating current stimulation (tACS) on major depressive disorder (MDD) was not confirmed.
OBJECTIVE
To evaluate the feasibility, safety, and efficacy of tACS as an add-on treatment for the symptoms of depression and to understand how tACS affects brain activity.
METHODS
The 4-week, double-blind, randomized, sham-controlled trial was performed from January 29, 2023 to December 22, 2023. Sixty-six participants were recruited and randomly assigned to receive 20 40-min sessions of either active (77.5Hz, 15mA) or sham stimulation, with one electrode on the forehead and two on the mastoid, each day (n = 33 for each group) for four weeks (till Week 4). The participants were followed for 4 more weeks (till Week 8) without stimulation for efficacy/safety assessment. During the 4-week trial, all participants were required to take 10-20mg of escitalopram daily. The primary efficacy endpoint was the change in HAMD-17 scores from baseline to Week 4 (with 20 treatment sessions completed). Resting-state electroencephalography (EEG) was collected with a 64-channel EEG system (Brain Products, Germany) at baseline and the Week 4 follow-up. The chi-square test, Fisher's exact test, independent-sample t-test, or Wilcoxon rank-sum test were used, as appropriate, to compare the differences in variables between groups. The effect of the intervention on the HAMD-17 score was also evaluated with linear mixed modeling (LMM) as sensitivity analysis. The correlation between the mean reduction in EEG and the mean reduction in the HAMD-17 total score was evaluated using Spearman correlation analysis.
RESULTS
A total of 66 patients (mean [SD] age, 28.4 [8.18] years; 52 [78.8%] female) were randomized, and 57 patients completed the study. Significant differences were found in the reductions in the HAMD-17 scores at Week 4 (t=3.44, P=0.001). Response rates at Week 4 were significantly higher in the active tACS group than in the sham tACS group (22 out of 33 patients [66.7%] versus 11 out of 33 [33.3%], P=0.007). In the active tACS group, a correlation between the mean change in alpha power and HAMD-17 scores at Week 4 was found (r=2.38, P=0.024), and the mean change in alpha power was significantly bigger for responders (Z=2.46, P=0.014). No serious adverse events were observed in this trial.
CONCLUSION
The additional antidepressant effect of tACS is significant, and the combination of tACS with antidepressants is a feasible and effective approach for the treatment of MDD. The antidepressant mechanism of tACS may be the reduction in alpha power in the left frontal lobe. Future research directions may include exploring more appropriate treatment parameters of tACS.
PubMed: 38880208
DOI: 10.1016/j.brs.2024.06.004 -
Progress in Neuro-psychopharmacology &... Jun 2024The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic... (Review)
Review
BACKGROUND
The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD.
METHODS
PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected.
RESULTS
Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1β, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients.
CONCLUSION
Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.
PubMed: 38879067
DOI: 10.1016/j.pnpbp.2024.111056 -
Journal of Psychiatric Research Jun 2024Combinations of Chinese patent medicines (CPM) with antidepressants (including selective serotonin reuptake inhibitors (SSRI), selective serotonin-norepinephrine... (Review)
Review
BACKGROUND
Combinations of Chinese patent medicines (CPM) with antidepressants (including selective serotonin reuptake inhibitors (SSRI), selective serotonin-norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA), and noradrenergic and specific serotonergic antidepressants (NaSSA)) are frequently utilized for treating depression in adults. However, the efficacy and safety of these combination treatments remain to be established.
METHODS
Systematic search was conducted in seven electronic databases, regulatory websites and international registers of trials from 1994 to 2023 that included adult patients with depressive disorders who received CPM combined with antidepressants. The Multiple-Treatment Meta-Analysis (MTMA) was conducted using a random effects model with Stata/MP17 and R4.3.5 software. Primary outcomes were total efficacy rate, Hamilton Depression Scale (HAMD) score, and Treatment Emergency Symptom Scale (TESS) score. Secondary outcomes included brain-derived neurotrophic factor (BDNF) levels.
RESULTS
A total of 146 randomized controlled trials (13,754 participants: 6929 in intervention and 6825 in control groups) were included. For total effective rate, Multiple-Treatment Meta-Analysis results showed that the overall effect of combined intervention was better compared with antidepressants alone, where Jieyuanshenkeli (JYASKL) presented the optimal option for improving total efficacy (OR = 5.39, 95% CI [2.60, 11.18], SUCRA = 84.50%). In reduding the HAMD, Shuganjieyujiaonang (SGJYJN) was most likely to reduce the HAMD score (SMD = -2.20, 95% CI [-3.06, -1.33], SUCRA = 86.10%), Jieyuanshenkeli (JYASKL),Tianewangbuxindan (TWBXD), Shuyukeli (SYKL), Anshenbuxinwan (ASBXW) combination intervention did not appear to be statistically superior to antidepressants alone. In theTreatment Emergency Symptom Scale (TESS), Wulinjiaonang induced the most significant reduction in TESS score (SMD = -1.98, 95% CI [-3.59, -0.36], SUCRA = 90.40%). Tianmengjiaonang (TMJN) + Antidepressants(AD) (SUCRA = 88.30%) displayed the highest scores in increasing the levels of BDNF, although not statistically significant compared to Antidepressants(AD) alone (SMD = 1.23, 95% CI [0.90, 1.55]).
CONCLUSION
Combinations of CPM and antidepressants showed superior efficacy over antidepressants alone. The optimal combinations were determined as Shuganjieyu Jiaonang (SGJYJN)/SSRIs and Jieyuanshenkeli (JYASKL)/SSRIs. In terms of safety, results showed that combination therapy did not show better TESS efficacy than antidepressants alone.Although some of the combination interventions were not superior than antidepressants alone in reducing HAMD scores,our findings provide a potentially significant alternative option for clinical complementary therapy. However, these results require further validation through larger sample sizes, multicenter randomized controlled trials, and real-world data.
PubMed: 38878648
DOI: 10.1016/j.jpsychires.2024.06.017 -
Eating Behaviors Jun 2024To examine rates and predictors of attrition from referral through to treatment completion in an outpatient public psychology service's eating disorder program in Perth,...
OBJECTIVE
To examine rates and predictors of attrition from referral through to treatment completion in an outpatient public psychology service's eating disorder program in Perth, Western Australia.
METHOD
The proportion (number) of clients (N = 671; mean age = 23.8 years) transitioning between stages of pre-treatment and treatment was identified. Associations between demographic, treatment and clinical variables and attrition were investigated using logistic regression.
RESULTS
Only 34% (n = 230) of referred patients started treatment and 16% (n = 107) completed treatment. Referral acceptance was correlated with provisional diagnoses that meet the service's inclusion criteria, and attendance at an initial assessment was correlated with younger age. Treatment commencement was correlated with the presence of a co-occurring depressive or anxiety disorder, and no previous suicide attempts. Completing a full course of treatment was correlated with no previous hospitalisation for psychiatric issues, no previous suicide attempts, a history of psychiatric medication use, and treatment with family-based therapy.
DISCUSSION
High rates of attrition were found from referral to treatment completion. A suggested framework for defining the different stages of attrition is proposed to allow for consistency of attrition reporting across the mental health field. Future studies are needed to identify why clients disengage following referral, assessment, and treatment commencement, to inform strategies to engage and sustain engagement and to optimise outcomes.
PubMed: 38878603
DOI: 10.1016/j.eatbeh.2024.101898 -
Women's Health (London, England) 2024Premenstrual dysphoric disorder is a depressive disorder affecting 5%-8% of people with menstrual cycles. Despite evidence that facial emotion detection is altered in...
BACKGROUND
Premenstrual dysphoric disorder is a depressive disorder affecting 5%-8% of people with menstrual cycles. Despite evidence that facial emotion detection is altered in depressive disorders, with enhanced detection of negative emotions (negativity bias), minimal research exists on premenstrual dysphoric disorder.
OBJECTIVES
The goal of this study was to investigate the effect of premenstrual dysphoric disorder symptoms and the premenstrual phase on accuracy and intensity at detection of facial emotions.
DESIGN
Cross-sectional quasi-experimental design.
METHOD
The Facial Emotion Detection Task was administered to 72 individuals assigned female at birth with no premenstrual dysphoric disorder ( = 30), and provisional PMDD ( = 42), based on a retrospective -based measure of premenstrual dysphoric disorder. Facial emotion detection was examined both irrespective of menstrual cycle phase, and as a function of premenstrual phase (yes, no). The task used neutral-to-emotional facial expression morphs (15 images/morph). Participants indicated the emotion detected for each image within the progressive intensity morph. For all six basic emotions (sad, angry, fearful, happy, disgust, and surprise), two scores were calculated: accuracy of responses and the intensity within the morph at which the correct emotion was first detected (image number).
RESULTS
Individuals reporting moderate/severe symptoms of premenstrual dysphoric disorder had more accurate and earlier detection of disgust, regardless of cycle phase. In addition, those with provisional premenstrual dysphoric disorder detected sad emotions earlier. A premenstrual dysphoric disorder group × cycle phase interaction also emerged: individuals reporting premenstrual dysphoric disorder symptoms were more accurate at detecting facial emotions during the premenstrual phase compared to the rest of the cycle, with a large effect size for sad emotions.
CONCLUSION
The findings suggest enhanced facial emotion processing in individuals reporting symptoms of premenstrual dysphoric disorder, particularly for sadness and disgust. However, replication is required with larger samples and prospective designs. This premenstrual dysphoric disorder premenstrual emotion detection advantage suggests an adaptive cognitive mechanism in premenstrual syndrome/premenstrual dysphoric disorder, and challenges stigma surrounding premenstrual experiences.
Topics: Humans; Female; Premenstrual Dysphoric Disorder; Cross-Sectional Studies; Emotions; Adult; Facial Expression; Menstrual Cycle; Young Adult; Premenstrual Syndrome
PubMed: 38877749
DOI: 10.1177/17455057241259176