Antidepressant Therapy Research Articles

Clinical features of coronary artery disease and 5-year survival of patients after myocardial infarction against the background of depressive disorders

Aim. To assess the features of the clinical picture of coronary artery disease (CAD) and the prognosis of patients with myocardial infarction with depressive disorder (DD).
 Materials and methods. We examined 101 patients with stable CAD who had myocardial infarction more than six months ago: 67 CAD patients with depression (Group 1) and 34 CAD patients without depression (Group 2). The clinical picture of CAD was assessed by complaints, angina self-monitoring diaries, and exercise tests. The presence and severity of DD was determined using psychometric scales: BDI (Beck Depression Scale), HADS (Hospital Anxiety and Depression Scale) and the opinion of a psychiatrist. Five-year survival information was obtained through telephone interviews with patients and their relatives.
 Results. In patients with CAD and DD in comparison with patients without DD self-monitoring diaries revealed more frequent angina attacks: 9 [6; 12] vs 6 [4; 7] per week (p=0.0001), the greater need for sublingual nitrates: 2 [0; 9] pills vs 0 [0; 4] pills (p=0.0001). DD significantly reduced exercise tolerance: 370 [250; 450] meters vs 435 [350; 500] meters using the six-minute walk test (p=0.04), according to the results of bicycle ergometry – 50 [25; 75] W vs 75 [50; 75] W (p=0.03). After 5 years of follow-up patients with comorbidities (CAD and DD) had a greater number of deaths: 13 (19.4%) vs 2 (5.9%), respectively, survived – 54 (80.6%) vs 32 (94.1%) (Gehan–Wilcoxon test, p=0.04).
 Conclusion. The comorbidity CAD and DD leads to a worsening of the clinical course of CAD and prognosis, which actualizes the need for verification of the diagnosis of DD and timely prescription of antidepressant therapy.

The enigma of depression in corticobasal degeneration, a frequent but poorly understood co-morbidity.

Depression is one of the most frequent neuropsychiatric symptoms in corticobasal degeneration (CBD), a rare, sporadic, and late-onset progressive neurodegenerative disorder of unknown etiology. It is clinically characterized by a levodopa-poorly responsible akinetic-rigid syndrome, apraxia, limb dystonia, cognitive, mood, behavioral, and language disorders. This 4-repeat (4R) tauopathy is morphologically featured by asymmetric frontoparietal atrophy, neuronal loss, and gliosis in cortex and subcortex including substantia nigra, ballooned/achromatic neurons with filamentous 4R tau aggregates in cortex and striatum, widespread thread-like structures, pathognomonic "astroglial plaques", "tufted astrocytes", and numerous "coiled bodies" (in astrocytes and oligodendroglia) in cerebral white matter. CBD is non-specific, as pathologically proven cases include several clinical phenotypes. Pubmed and Google Scholar were systematically analyzed until October 2023, with focus on the prevalence, clinical manifestation, neuroimaging data, and treatment options of depression in CBD. Its prevalence is about 30-40% which is more frequent than in most other atypical parkinsonian syndromes. Depression usually does not correlate with motor and other clinical parameters, suggesting different pathophysiological mechanisms. Asymmetric atrophy and hypometabolism of frontoparietal cortical areas are associated with disruption of fronto-subcortical circuits, nigrostriatal dopaminergic, and cholinergic deficiency. Since no specific neuroimaging, neuropathological, or biomarker studies of depression in CBD are available, its pathobiological mechanisms and pathogenesis are poorly understood. Antidepressive therapy may be useful, but is often poorly tolerated. Depression in CBD, like in other parkinsonian syndromes, may be related to multi-regional patterns of cerebral disturbances and complex pathogenic mechanisms that deserve further elucidation as a basis for early diagnosis and adequate treatment to improve the quality of life in this fatal disease.

A Retrospective Case-Control Study on the Differences in the Effectiveness of Theta-Burst Stimulation Therapy for Depression with and without Antidepressant Medication.

Transcranial magnetic stimulation (TMS) therapy has few side effects and comparable therapeutic effects to antidepressant treatment, but few studies have introduced TMS therapy as an initial treatment for MDD. The objective of this study was to retrospectively compare the clinical outcomes between 50 MDD patients without antidepressants (i.e., TMS monotherapy) and 50 MDD patients with antidepressants plus TMS therapy, matched for age, sex, and depression severity. The presence or absence of antidepressant therapy in first-line treatment was determined via a detailed interview by psychiatrists. The study design was a retrospective observational case-control study using the TMS registry data. The key inclusion criteria were adult patients who met the diagnosis of MDD and received 20-30 sessions of intermittent theta-burst stimulation (iTBS) therapy to the left dorsolateral prefrontal cortex (DLPFC). In this study, the Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary outcome measure. No significant group differences existed in the baseline MADRS total score between the unmedicated and medicated patient groups. Following TMS therapy, no significant group differences in response rate, remission rate, or relative total score change in the MADRS were observed. The main limitations were the retrospective design and the use of registry data as a source. Our findings suggest that TMS monotherapy may be as effective as TMS add-on therapy to antidepressants when used as the first-line therapy for MDD, but randomized controlled trials are needed.

Molecular Mechanisms of Reelin in the Enteric Nervous System and the Microbiota-Gut-Brain Axis: Implications for Depression and Antidepressant Therapy.

Current pharmacological treatments for depression fail to produce adequate remission in a significant proportion of patients. Increasingly, other systems, such as the microbiome-gut-brain axis, are being looked at as putative novel avenues for depression treatment. Dysbiosis and dysregulation along this axis are highly comorbid with the severity of depression symptoms. The endogenous extracellular matrix protein reelin is present in all intestinal layers as well as in myenteric and submucosal ganglia, and its receptors are also present in the gut. Reelin secretion from subepithelial myofibroblasts regulates cellular migration along the crypt-villus axis in the small intestine and colon. Reelin brain expression is downregulated in mood and psychotic disorders, and reelin injections have fast antidepressant-like effects in animal models of depression. This review seeks to discuss the roles of reelin in the gastrointestinal system and propose a putative role for reelin actions in the microbiota-gut-brain axis in the pathogenesis and treatment of depression, primarily reflecting on alterations in gut epithelial cell renewal and in the clustering of serotonin transporters.

Ferroptosis: a new antidepressant pharmacological mechanism.

The incidence rate of depression, a mental disorder, is steadily increasing and has the potential to become a major global disability factor. Given the complex pathological mechanisms involved in depression, the use of conventional antidepressants may lead to severe complications due to their side effects. Hence, there is a critical need to explore the development of novel antidepressants. Ferroptosis, a newly recognized form of cell death, has been found to be closely linked to the onset of depression. Several studies have indicated that certain active ingredients can ameliorate depression by modulating the ferroptosis signaling pathway. Notably, traditional Chinese medicine (TCM) active ingredients and TCM prescriptions have demonstrated promising antidepressant effects in previous investigations owing to their unique advantages in antidepressant therapy. Building upon these findings, our objective was to review recent relevant research and provide new insights and directions for the development and application of innovative antidepressant strategies.

Association between Depressive Mood, Antidepressant Therapy and Neuropsychological Performances: Results from a Cross-Sectional Study on Elderly Patients.

Currently, the global demographic landscape is undergoing a transformative shift towards an increasingly aging population. This leads to an increase in chronic pathologies, including depression and cognitive impairment. This study aimed to evaluate the association between depressive mood, whether in treatment or not, and cognitive capacities, assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). This study included 259 subjects, aged 65 years or older, evaluated at the Geriatric Outpatient Service of the University Hospital of Monserrato, Cagliari, between July 2018 and May 2022, who experienced subjective depressive mood and/or cognitive deficits. Only 25.1% of the sample showed no cognitive impairment on the RBANS. Education was a significant regressor of the RBANS Total Scale scores (p < 0.0001) and was negatively associated with mood deflection (r = -0.15, p = 0.0161). Subjects with depressive mood had more impaired attention and visuospatial/constructional abilities compared to untreated euthymic patients. Post-hoc analysis, conducted with the Conover test, showed that untreated euthymic patients (GDS-15 ≤ 5, group 2) had a higher score on the RBANS total scale than patients with mood deflection (GDS-15 > 5, group 1), and treated euthymic patients (GDS-15 ≤ 5, group 3). Finally, different logistic regression analyses revealed a significant negative coefficient for GDS as a regressor of the RBANS total scale (coefficient: -0.04, p = 0.0089), visuospatial/constructional abilities (coefficient: -0.03, p = 0.0009), language (coefficient: -0.05, p = 0.0140), and attention (coefficient: -0.05, p < 0.0001). Our analysis demonstrated that "naturally" euthymic people show better cognitive performances than people with depressive mood and subjects with acceptable mood due to antidepressants. Furthermore, the gender-based difference observed in the language domain suggests the potential utility of incorporating an alternative category for male patients in the Semantic Fluency test.

Patient satisfaction with the quality of care received is associated with adherence to antidepressant medications.

There is a paucity of evidence on the association between satisfaction with quality of care and adherence to antidepressants. To examine the association between patient satisfaction with healthcare and adherence to antidepressants. A cohort study design was used to identify antidepressant users from the 2010-2016Medical Expenditure Panel Survey data, a national longitudinal complex survey study design on the cost and healthcare utilization of the noninstitutionalized population in the United States. The Consumer Assessment of Healthcare Providers and Systems were used to measure participants' satisfaction with access and quality of care, patient-provider communication and shared decision-making (SDM). Patients were considered satisfied if they ranked the quality of care at ≥9 (range: 0[worst]- 10[best]). Antidepressant adherence was measured based on medication refill and complete discontinuation. MEPS sampling survey-weighted multivariable-adjusted logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between satisfaction and adherence to antidepressants. We tested for the potential presence of reverse associations by restricting the analysis to new users of antidepressants. The roles of patient-provider communication and SDM on the satisfaction-adherence association were examined through structural equation models (SEM). Among 4,990 (weighted counts = 8,661,953) antidepressant users, 36% were adherent while 39% discontinued antidepressants therapy. Half of antidepressant users were satisfied with the healthcare received. Satisfied patients were 26% (OR = 1.26, 95%CI: 1.08, 1.47) more likely to adhere and 17% (OR = 0.83, 95%CI: 0.71, 0.96) less likely to discontinue, compared to unsatisfied antidepressant users. Patient satisfaction was also associated with higher odds (OR = 1.41, 95%CI: 1.06, 1.88) of adherence among a subgroup of new users of antidepressants. The SEM analysis revealed that satisfaction was a manifestation of patient-provider communication (β = 2.03, P-value<0.001) and SDM (β = 1.14, P-value<0.001). Patient satisfaction is a potential predictor of antidepressant adherence. If our findings are confirmed through intervention studies, improving patient-provider communication and SDM could likely drive both patient satisfaction and adherence to antidepressants.

Diagnostic psychiatric and somatic comorbidity in patients with depression in the Western Balkan countries.

This paper aims to examine the frequency and significance of diagnostic comorbidity of psychiatric disorders and somatic diseases in a sample of patients with depression as well as present current psychopharmacological treatment of the patients in the sample. The subjects in this study sample were 489 patients from the four Western Balkan countries with current primary diagnosis of major depression according to ICD 10. Comorbid psychiatric disorders and non-psychiatric illnesses were noted according to ICD 10 criteria during the diagnostic interview and analysed later. Additionally, the pharmacological treatment (existing and newly introduced) for each patient was noted and analysed later. At least one comorbid psychiatric disorder was present in 72.5% of patients. The most frequent were anxiety disorders (53.6%), specifically generalized anxiety disorder (20.2%); non-organic sleep disorders (50.7%), specifically insomnia (48.4%); and sexual dysfunctions (21.4%), specifically lack of sexual desire (20.2%). Comorbidity with any non-psychiatric illness was present in 80.3% of patients. The most frequent were circulatory system diseases (55.9%), specifically hypertension (45.9%); endocrine, nutritional and metabolic disorders (51.3%), specifically hyperlipidaemia (24.0%); and other non-psychiatric disorders (60.7%), specifically low back pain (22.7%). All patients received pharmacological treatment with different medications. Most patients received monotherapy or combination therapy of antidepressants, anxiolytics, antipsychotics and antiepileptics. The most frequently used antidepressants were escitalopram, sertraline, and duloxetine. The most frequently used anxiolytics were alprazolam and diazepam, the most used antiepileptic was pregabalin, and the most used antipsychotics were olanzapine, quetiapine, and aripiprazole. The results of the study confirm the results of previous research studies about the high prevalence of psychiatric and non-psychiatric comorbidities in patients with depression that were conducted in the past. It would be important if future studies could prove the importance of those comorbidities on clinical severity, choice of treatment, and its outcome in patients with depression.

THE IMPACT OF AGOMELATINE AND MELATONIN ON HUMAN COLORECTAL CANCER: AN IN VITRO INVESTIGATION

Aim: Colorectal cancer (CRC) affects approximately one million people worldwide each year, with 500,000 deaths annually. In our country, CRC ranks as the third most common cancer in women and the fourth in men. Melatonin, a hormone with well-established antioxidant and anti-cancer properties, is produced by the pineal gland. Agomelatine, a recent addition to our antidepressant therapies, also acts on melatonin receptors and may offer therapeutic benefits in cancer treatment. This study investigates the effects of melatonin and agomelatine on the viability of human colorectal cancer cell lines (HCT-116 and Caco-2). Materials and Methods: We treated HCT-116 and Caco-2 cell lines with melatonin and Agomelatine dissolved in 96% ethanol at concentrations of 0.1, 1, 5, and 10 mM for 24 hours. Cell viability was measured using 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolyum bromide (MTT) assay. Statistical analyses were performed using IBM SPSS Statistics 24.0, applying Bonferroni correction and the Mann-Whitney U-test, with significance set at p&lt;0.05. The half-maximal inhibitory concentration (LogIC50) was calculated from the MTT assay results. Results: All tested concentrations of melatonin and agomelatine significantly reduced cell viability in both HCT-116 and Caco-2 cell lines (p&lt;0.05). Conclusion: The study demonstrates that both agomelatine and melatonin possess significant cytotoxic and anti-tumor effects against human colorectal cancer cells.

Pharmacogenomic and pharmacometabolomic biomarkers of the efficacy and safety of antidepressants: focus on selective serotonin reuptake inhibitors

The efficacy and safety of psychopharmacotherapy with antidepressants is of great medical importance. The search for clinical and biological predictors for choosing the optimal psychopharmacotherapy with antidepressants is actively underway all over the world. Research is mainly devoted to searching for associations of polymorphic gene variants with the efficacy and safety of therapy. However, information about a patient's genetic polymorphism is often insufficient to predict the efficacy and safety of a drug. Modern research on the personalization of pharmacotherapy should include, in addition to genetic, phenotypic biomarkers. This is important because genotyping, for example, cannot accurately predict the actual metabolic activity of an isoenzyme. To personalize therapy, a combination of methods is required to obtain the most complete profile of the efficacy and safety of the drug. Successful treatment of depression remains a challenge, and inter-individual differences in response to antidepressants are common. About half of patients with depressive disorders do not respond to the first attempt at antidepressant therapy. Serious side-effects of antidepressant pharmacotherapy and discontinuation of treatment due to their intolerance are associated with ineffective therapy. This review presents the results of the latest studies of «omics» biomarkers of the efficacy and safety of antidepressants.

Exploring the management and treatment of IBD from the perspective of psychological comorbidities.

The prevalence of anxiety, depression, and other psychological comorbidities among patients with inflammatory bowel disease (IBD) significantly exceeds that of the general population. Moreover, a bidirectional relationship exists between psychological comorbidities and IBD. This intricate interplay has substantial clinical implications, impacting treatment adherence, therapeutic efficacy, and disease recurrence rates. In this review, we explore the multifaceted mechanisms through which psychological factors influence IBD progression, treatment response, and prognosis. Specifically, we delve into the involvement of the hypothalamic-pituitary-adrenal axis, autonomic nervous system, enteric nervous system, microbiota-gut-brain axis, systemic inflammatory cytokines, and immune cell function. Additionally, we discuss the potential benefits of antidepressant therapy in mitigating IBD risk and the role of psychotropic drugs in reducing peripheral inflammation. Recognizing and addressing psychological comorbidity is pivotal in comprehensive IBD management. We advocate for the integration of biopsychosocial approaches into IBD treatment strategies, emphasizing the need for innovative psychological interventions as adjuncts to conventional therapies. Rigorous research investigating the impact of antidepressants and behavioral interventions on IBD-specific outcomes may herald a paradigm shift in IBD management.

C-Reactive Protein As A Response Indicator In Drug-Naïve Patients With Major Depressive Disorder: A Hospital-Based Study

Abstract Objective: C-reactive protein (CRP) is an indicator of the inflammatory process in the body, and is associated with the pathogenesis of depression through its purported effect on neurotransmitter function in the brain. Current research aims to study the relationship between the levels of CRP and the rate of remission of major depressive disorder with first-line antidepressant therapy. Methods: This hospital-based prospective study included thirty patients by purposive sampling technique. Patients with first-episode MDD with no history of antidepressant exposure and other medical comorbidity were recruited for pharmacotherapy with escitalopram, a first-line antidepressant. Patients taking antidepressants, anti-inflammatory medicines, having co-morbid conditions or other psychiatric conditions were excluded. The baseline CRP levels were measured and depressive symptoms were evaluated using the Hamilton Rating Scale for Depression (HRSD) at weeks 0, 6 and 12. The patients with low (≤5 mg/l) and high (&gt;5 mg/l) CRP levels were compared for remission rates at week 12 using Kaplan–Meier survival analysis. Results: Amongst the 30 cases, 11(36.7%) were males and 19(63.3%) were female patients. The mean age was 35.95±7.85 years. Both groups were matched concerning age, gender, BMI and baseline HRSD score (p&gt;0.05). As per Kaplan–Meier survival analysis, a significantly higher proportion of patients had remission of MDD at the 12th week having CRP levels ≤5 mg/l than the patients with CRP levels &gt;5 mg/dl (p=0.002). Conclusion: This research concluded that after an adequate trial with a standard antidepressant, higher levels of CRP could lead to poorer remission rates in MDD subjects and could represent a sub-group of patients with treatment resistance.

Depression and comorbid obstructive sleep apnea: Association between positive airway pressure adherence, occurrence of self-harm events, healthcare resource utilization, and costs

ObjectivePrevious studies have shown that treatment of obstructive sleep apnea (OSA) with positive airway pressure (PAP) therapy in patients with depression may improve depression symptoms and response to antidepressant therapy. We investigated the association between PAP therapy adherence, self-harm events, healthcare resource utilization (HCRU), and costs over 2 years in a national sample of patients with pre-existing depression and newly diagnosed comorbid OSA. MethodsAdministrative claims data were linked to objective PAP therapy usage. Inverse probability treatment weighting was used to compare outcomes over 2 years across PAP adherence levels. The predicted numbers of emergency room (ER) visits and hospitalizations by adherence level were assessed using risk-adjusted generalized linear models. Results37,459 patients were included. Relative to non-adherent patients, consistently adherent patients had fewer self-harm events (0.04 vs 0.05, p < 0.001) after 1 year, and significantly (all p < 0.001) fewer ER visits (0.66 vs 0.86) and all-cause hospitalizations (0.13 vs 0.17), and lower total ($11,847 vs $11,955), inpatient hospitalization ($1634 vs $2274), and ER visit ($760 vs $1006) costs per patient in the second year of PAP therapy. Consistently adherent patients showed lower risk for hospitalizations and ER visits. LimitationsUsing observational claims data, we were unable to assess clinical characteristics including sleep, sleepiness, and daytime symptoms, or important social determinants of health. We were limited in assessing care received outside of the included health plans. ConclusionConsistent adherence to PAP therapy over 2 years was associated with improved HCRU outcomes for patients with pre-existing depression newly diagnosed with comorbid OSA.

Pharmacotherapy for the Prevention of Depression and Behavioral Side Effects in Hematopoietic Stem Cell Transplantation Patients

Depression and decreased quality of life (QoL) develop in approximately 30% of nondepressed hematopoietic stem cell transplantation (HSCT) recipients early after transplantation. To potentially prevent this complication, we conducted a prospective randomized trial to assess whether prophylaxis of nondepressed HSCT patients with the antidepressant sertraline (SER) in addition to supportive psychotherapy starting at admission for transplantation decreases the risk of depression and improves QoL. The primary objective of the study was to evaluate whether there was an added benefit of SER versus placebo along with routine supportive psychotherapy on the development of depression in patients receiving HSCT. A secondary objective was to analyze the impact on patient-reported QoL and survival. The study was conducted at a single-site academic medical center. We randomized 123 nondepressed HSCT recipients (1:1) in a phase III double-blind study to receive SER starting at a dose of 50 mg/day, with possible dose escalations to 200 mg per day, or placebo beginning on admission for HSCT and continuing for 12 weeks. Supportive psychotherapy was provided for both groups. Depression (Beck Depression Inventory II [BDI-II]) and QoL (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation [FACT-BMT]) were assessed prior to HSCT and then weekly to week 12 post-HSCT. A multivariable linear mixed-effects model was used to estimate the mean change in BDI-II scores as a function of elapsed time since baseline, treatment assignment, and their interaction. The same process was used to assess treatment effects on all QoL scores from the FACT-BMT assessment. A Kaplan-Meier curve was used to estimate the probability of survival for each group following initiation of treatment. A follow-up Cox proportional hazards model was used to estimate the mortality rate in the 2 groups. Our results do not indicate a benefit of SER in either a diminished risk of depression or improved QoL or survival outcomes. Based on our findings, we can only recommend early evaluation of HSCT recipients for depression, with antidepressant use reserved for patients with evidence of clinical depression, unless additional randomized trials can confirm the effects of early antidepressant therapy on mood and QoL in this vulnerable group. Future research in this area would be improved by systematic monitoring of medication adherence, identification of the optimal dose of SER (or other antidepressant), and inclusion of psychotherapy outcomes when relevant, the absence of which are limitations of this study.

Late onset psychosis treatment with adjunctive medicines.

A number of studies have shown the feasibility of using adjunctive drugs in late onset psychosis (LOP). Testing hypothesis that among LOP people treated with antipsychotics and antidepressants, basing on certain clinical characteristics a subgroup of patients might be distinguished, for whom adjunctive therapy is advantageous. This subgroup might be identified by measurement of blood biochemical parameters. 59 in-patients with LOP, treated neuroleptics and antidepressants, were included, and followed in real clinical practice. Database containing demographic, clinical data (scores by PANSS, CDSS, CGI-S, HAMD-17), prescribed therapy, adverse effects of antipsychotic and antidepressant treatment, and blood biochemical parameters (enzymatic activities of glutamate- and glutathione metabolism enzymes in platelets and erythrocytes) at baseline and after the treatment course was created. Three groups of patients (Gr1, Gr2, and Gr3), based on the adjunctive therapy usage were identified: Gr1 (n = 16) was without adjunctive therapy, two other groups (Gr2 and Gr3) were with adjunctive medicines, such as 2-ethyl-6-methyl-3-hydroxypyridine succinate (EMHS; Gr2, n = 20), or other drugs, such as citicoline, cerebrolysin, cortexin, actovegin, gliatilin (choline alfoscerate; Gr3, n = 23). The enzymatic activities were assessed also in the matched control group (n = 38). In all three patient groups, as compared with controls, activity of erythrocyte glutathione reductase was decreased at baseline and after the treatment course. In Gr2, unlike Gr1 or Gr3, there was a significant decrease in baseline glutamate dehydrogenase and glutathione-S-transferase activities. Certain clinical criteria were also elucidated for prescription of EMHS as adjunctive therapy for patients of Gr2. Glutamate dehydrogenase and glutathione-S-transferase activities returned closer to control levels after the treatment course in Gr2, unlike Gr1, where they declined yet more after psychotropic treatment without adjunctive medicine. Different significant links between biochemical parameters and scores by clinical scales were observed in Gr1, Gr2, and Gr3, some having predictive value for evaluation of antipsychotic treatment efficacy. We demonstrate the validity of adjunctive neuroprotective medicines' usage in addition to antipsychotic and antidepressant therapy in distinct subgroups of patients suffering with LOP, especially those who have prominent side effects accompanying their psychotropic treatment. Returning of biochemical parameters to control range following the treatment course observed in patients of the subgroup treated with adjunctive EMHS is evidence for their metabolism normalization.

ASSOCIATION BETWEEN CARDIOVASCULAR DISEASE AND COGNITIVE IMPAIRMENT: IS DEPRESSION A MEDIATOR?

Abstract By 2040, over 9 million US adults will live with dementia. Understanding the relationship between risk factors and cognitive decline is critical to prevent disease and slow progression. Depression and cardiovascular disease (CVD) are independent risk factors for cognitive impairment (CI) which may interact, suggesting depression may play a mediating role in the relationship between CVD and CI, an hypothesis explored in this study. Data from the Systolic Blood Pressure Intervention Trial (SPRINT), a multi-center, randomized, controlled trial were used in this multivariate logistic regression analysis. CI was defined as adjudicated cases of mild CI and probable dementia. Depression was defined as a Patient Health Questionnaire-9 score ≥10 or current antidepressant therapy. We developed a CVD risk score using data from SPRINT participants and discretized the scores into tertiles. Of 9259 SPRINT participants, our analytic sample included 8456 who had adjudicated mild CI or dementia and had baseline depression scores. They were on average 68 years and 36% were female. After adjusting for age, sex, education, race, prior CVD, chronic kidney disease and treatment assignment, participants with high cardiovascular risk were more likely to have CI (OR: 1.55, 95% CI: 1.17-2.05). Participants with depression were more likely to have CI (OR: 1.29, 95% CI: 1.05-1.58) however, the interaction between cardiovascular risk and cognition was not significant. Findings from this study suggest that while depression and CVD are associated with CI, depression may not explain the CVD-CI relationship. More research is needed to understand the relationship between depression, CVD and CI.

Unveiling the Psychedelic Journey: An Appraisal of Psilocybin as a Profound Antidepressant Therapy.

Depression, a global health concern with significant implications for suicide rates, remains challenging to treat effectively with conventional pharmacological options. The existing pharmaceutical interventions for these illnesses need daily dosing, are accompanied by various adverse effects, and may exhibit limited efficacy in certain cases. However, hope emerges from an unlikely source-Psilocybin, a natural hallucinogen found in certain mushrooms. Recently, this enigmatic compound has garnered attention for its potential therapeutic benefits in addressing various mental health issues, including depression. Psilocybin alters mood, cognition, and perception by acting on a particular subtype of serotonin receptors in the brain. It's feasible that these shifts in consciousness will promote healing development, offering a novel approach to depression management. This comprehensive review explores psilocybin, derived from specific mushrooms, and its implications in the treatment of depression. The study examines new perspectives and therapeutic possibilities surrounding psilocybin, addressing existing gaps in academic literature. It delves into its biosynthesis, unique mechanisms of action, therapeutic applications, and anti-depressive effects. By uncovering the potential of this mind-altering substance, the review aims to advance psychiatric care, offering hope to those globally affected by depression.

Application of psilocybin in mental health disorders

Psilocybin is a naturally occurring psychoactive compound, which has been used for ages in traditional settings for religious and therapeutic use. Recent studies have renewed interest in psilocybin for its potential therapeutic benefits in treating depression and anxiety. The pharmacodynamics of psilocybin are complex, involving its rapid conversion to psilocin and its activity on various serotonin receptors, particularly the 5HT2A/C and 5HT1A receptors. In addition, psilocybin can increase glutamate release, which is believed to be an important mechanism underlying its therapeutic effects. Clinical trials have demonstrated that psilocybin has a long-lasting antidepressant effect, with little to no side effects. However, it is necessary to further study the mechanisms underlying its therapeutic potential and to optimize its use in clinical settings. Overall, the promising findings suggest that psilocybin may offer a valuable alternative to traditional antidepressant therapies for individuals suffering from depression and anxiety. Meanwhile, studies have shown that this drug also has certain benefits for mental disorders such as addiction and obsessive-compulsive disorder. Thus, it is necessary to continue exploring the potential of psilocybin as a novel strategy in treating mental health disorders.

Oral Candidiasis a common manifestation of xerostomia and chronic renal failure: A report of two case series

Candida species is a natural commensal in the oral cavity in around 53% of the population However, it becomes opportunistic in immune compromised situations and inpatients taking certain medications. The evaluation of risk variables is critical in the management of candidal infection. It is critical to precisely record medical history of the patient in order to know the exact underlying cause. This case report will highlight two candidiasis cases in patients with chronic renal disease and patient on antidepressant therapy.

Sigma-1 receptor activation mediates the sustained antidepressant effect of ketamine in mice via increasing BDNF levels.

Sigma-1 receptor (S1R) is a unique multi-tasking chaperone protein in the endoplasmic reticulum. Since S1R agonists exhibit potent antidepressant-like activity, S1R has become a novel target for antidepression therapy. With a rapid and sustained antidepressant effect, ketamine may also interact with S1R. In this study, we investigated whether the antidepressant action of ketamine was related to S1R activation. Depression state was evaluated in the tail suspension test (TST) and a chronic corticosterone (CORT) procedure was used to induce despair-like behavior in mice. The neuronal activities and structural changes of pyramidal neurons in medial prefrontal cortex (mPFC) were assessed using fiber-optic recording and immunofluorescence staining, respectively. We showed that pharmacological manipulation of S1R modulated ketamine-induced behavioral effect. Furthermore, pretreatment with an S1R antagonist BD1047 (3 mg·kg-1·d-1, i.p., for 3 consecutive days) significantly weakened the structural and functional restoration of pyramidal neuron in mPFC caused by ketamine (10 mg·kg-1, i.p., once). Ketamine indirectly triggered the activation of S1R and subsequently increased the level of BDNF. Pretreatment with an S1R agonist SA4503 (1 mg·kg-1·d-1, i.p., for 3 consecutive days) enhanced the sustained antidepressant effect of ketamine, which was eliminated by knockdown of BDNF in mPFC. These results reveal a critical role of S1R in the sustained antidepressant effect of ketamine, and suggest that a combination of ketamine and S1R agonists may be more beneficial for depression patients.