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One of the most prevalent psychiatric disorders is major depressive disorder (MDD), which increases the probability of suicidal ideation or untimely demise. Abnormal frontal hemodynamic changes detected by functional near-infrared spectroscopy (fNIRS) during verbal fluency task (VFT) have the potential to be used as an objective indicator for assessing clinical symptoms. However, comprehensive quantitative and objective assessment instruments for individuals who exhibit symptoms suggestive of depression remain undeveloped. Drawing from a total of 467 samples in a large-scale dataset comprising 289 MDD patients and 178 healthy controls, fNIRS measurements were obtained throughout the VFT. To identify unique MDD biomarkers, this research introduced a data representation approach for extracting spatiotemporal features from fNIRS signals, which were subsequently utilized as potential predictors. Machine learning classifiers (e.g., Gradient Boosted Decision Trees (GBDT) and Multilayer Perceptron) were implemented to assess the ability to predict selected features. The mean and standard deviation of the cross-validation indicated that the GBDT model, when combined with the 180-feature pattern, distinguishes patients with MDD from healthy controls in the most effective manner. The accuracy of correct classification for the test set was 0.829 ± 0.053, with an AUC of 0.895 (95 % CI: 0.864–0.925) and a sensitivity of 0.914 ± 0.051. Channels that made the most important contribution to the identification of MDD were identified using Shapley Additive Explanations method, located in the frontopolar area and the dorsolateral prefrontal cortex, as well as pars triangularis Broca's area. Assessment of abnormal prefrontal activity during the VFT in MDD serves as an objectively measurable biomarker that could be utilized to evaluate cognitive deficits and facilitate early screening for MDD. The model suggested in this research could be applied to large-scale case-control fNIRS datasets to detect unique characteristics of MDD and offer clinicians an objective biomarker-based analytical instrument to assist in the evaluation of suspicious cases. • fNIRS during VFT has the potential to be used as an objective indicator for assessing MDD. • The study developed an interpretable machine learning framework for screening patients with MDD from healthy controls. • The classification of model for MDD diagnosis had a mean accuracy of 0.829, with an AUC of 0.895. • The model could be applied to large-scale case-control fNIRS datasets to identify neuroimaging biomarkers and offer clinicians an objective instrument. [ABSTRACT FROM AUTHOR]

While PTSD is commonly associated with multiple comorbidities, studies have yet to quantify the impact of these comorbidities on key clinical outcomes and HCRU. This study explored risks of emergency room (ER) visits, inpatient admissions (IA), suicidal ideation (SI), and treatment follow-up duration (FU), amongst PTSD patients with comorbid MDD and/or SUD. Using real-world data (RWD) generated by electronic health records accessed from the NeuroBlu database, a cohort of adolescent patients (12-17 yrs) was examined over a one-year study period following PTSD diagnosis. 5794 patients were included in the cohort. Compared to patients with only PTSD (n = 3061), those with comorbid MDD (n = 1820) had greater odds of ER (4.5 times), IA (1.6 times), and FU (4.3 times). Those with comorbid SUD (n = 653) had greater odds of IA (4.5 times), shorter FU (34 days), and lower odds of ER (0.5 times). Both comorbidities (n = 260) had greater odds of ER (3.8 times), IA (2.6 times), SI (3.6 times), and shorter FU (12 days). These RWD had a high proportion of missingness. Health records of patients who changed service providers could not be accounted for in this study. Both MDD and SUD substantially elevated the risk of HCRU and suicidal ideation for PTSD patients. • Limited literature studying the cumulative effects of major depressive disorder (MDD) and substance use disorder (SUD) on adolescents diagnosed with PTSD. • Comorbid MDD and SUD was respectively present in 31 % and 11 % of the 5794 adolescents diagnosed with PTSD. • Minimally, the odds of inpatient admission is at least 40 % higher in patients with comorbid MDD or SUD present, with the odds of patients with comorbid SUD being admitted to the hospital being 4.5 times higher than those with PTSD only. • Patients with both MDD and SUD were not observed to develop worse outcomes. • Screening for comorbid MDD and SUD may substantially improve prognosis of PTSD in adolescents. [ABSTRACT FROM AUTHOR]

Background: Major Depressive Disorder (MDD) is a leading cause of disability and results in excessive utilization of healthcare resources worldwide. The Middle East and North Africa (MENA) region shows a high prevalence of depressive disorders. Generalized Anxiety Disorder (GAD) and MDD have the highest rate of comorbidity of all mood and anxiety disorders, ranging from 40 to 98% in drug studies. Comorbid GAD results in more significant impairment in MDD and increases the severity of symptoms. Although several clinical trials supported the safety and effectiveness of vortioxetine, no data regarding these aspects has been revealed in the MENA region. This study aimed to assess the safety and efficacy of vortioxetine in patients with comorbid GAD in the United Arab Emirates (UAE). Method: In a multicenter observational study, 118 patients with confirmed anxiety and depressive disorders were evaluated over four visits (baseline visit, two weeks, four weeks, and eight weeks) using MADRS and HAM-A scales to assess depression and anxiety severity, respectively by calculating mean change and the percent using Kendall's W test. Results: A significant mean difference in MADRS score was observed, with a gradual decrease of mean MADRS total scores over the assessment weeks (p < 0.001) as well as in HAM-A scores, from severe to moderate-severe anxiety through the four visits (p < 0.001). Furthermore, only one case was reported as a serious side effect. Nausea and insomnia were the most predominant side effects reported among the studied population. Conclusion: Vortioxetine was found effective and safe among patients with MDD and comorbid GAD. [ABSTRACT FROM AUTHOR]

Major Depressive Disorder (MDD) poses significant public health challenges globally and in Southeast Asia, with substantial impairment and disease burden. Understanding its prevalence and associated risk factors is crucial for effective intervention. This study aims to describe the prevalence shifts, correlates, and comorbidities of MDD in Singapore. Data were collected from the second Singapore Mental Health Study (SMHS 2016), a national cross-sectional survey comprising 6126 adult residents. The WHO Composite International Diagnostic Interview assessed MDD and comorbidities. Statistical analyses, including logistic regression, were conducted to examine the associations and trends. The lifetime weighted prevalence of MDD in SMHS 2016 was 6.2 %, with an overall increase from 5.8 % in 2010. Significant associations were found between MDD and age, marital status, and comorbid physical disorders. Young adults and divorced/separated individuals exhibited higher MDD prevalence. Chronic pain was significantly associated with MDD. The study's cross-sectional design limits causal inference, and selective non-response might affect prevalence estimates. However, the study benefits from a large, nationally representative sample and standardized methodologies. Young and middle-aged adults, and divorced/separated individuals demonstrate elevated MDD prevalence, warranting targeted interventions. Individuals with comorbidities, particularly chronic pain, constitute a high-risk and vulnerable population. Comprehensive assessment and treatment plans should involve multidisciplinary teams and integrated care approaches to better address the complex needs of these individuals. Our study also highlights specific interventions for schools, families, communities, and workplaces. Despite Singapore's relatively low prevalence compared to Western nations, MDD remains cross-culturally valid emphasizing the need for early intervention and preventive public health measures. • Lifetime weighted prevalence of Major Depressive Disorder (MDD) was 6.2 %. • Young adults, and separated or divorced individuals, exhibited higher MDD prevalence. • Chronic pain showed the highest comorbidity with MDD. [ABSTRACT FROM AUTHOR]

Objectives: Mood disorders are trending to be among the leading causes of years lived with disability. Despite multiple treatment options, around 30% patients with major depressive disorder (MDD) develop treatment resistant depression (TRD) and fail to respond to current pharmacological therapies. This study aimed to explore the potential benefits of nutritional treatment strategies, along with their molecular mechanisms of action, focusing especially on low-carbohydrate diet (LCHD), ketogenic diet (KD) and other strategies based on carbohydrates intake reduction. Methods: A comprehensive literature review was conducted to determine the impact of LCHD on alleviating depressive symptoms in patients with MDD, along with an explanation of its mode of action. Results: The study revealed significant impact of nutritional interventions based on restriction in carbohydrate intake such as LCHD, KD or sugar-sweetened beverages (SSB) exclusion on anxiety or depression symptoms reduction, mood improvement and lower risk of cognitive impairment or depression. The efficacy of these approaches is further substantiated by their underlying molecular mechanisms, mainly brain-derived neurotrophic factor (BDNF) which is a potential key target of sugar restriction diets in terms of neuroplasticity. Discussion: Healthcare professionals may consider implementing LCHD strategies for MDD and TRD patients to modify the disease process, maintain euthymia, and prevent depressive episode relapses. Ranging from the exclusion of SSB to the adherence to rigorous LCHD regimens, these nutritional approaches are safe, straightforward to implement, and may confer benefits for well-being and relapse prevention in this specific patient population. [ABSTRACT FROM AUTHOR]

Background/Objectives: Major depressive disorder (MDD) is a mental health condition that can severely impact patients' social lives, leading to withdrawal and difficulty in maintaining relationships. Environmental factors such as trauma and stress can worsen MDD by interacting with genetic predispositions. Epigenetics, which examines changes in gene expression influenced by the environment, may help identify patterns linked to depression. This study aimed to explore the epigenetic mechanisms behind MDD by analysing six public datasets (n = 1125 MDD cases, 398 controls in blood; n = 95 MDD cases, 96 controls in brain tissues) from the Gene Expression Omnibus. Methods: As an innovative approach, two meta-analyses of DNA methylation patterns were conducted alongside an investigation of stochastic epigenetic mutations (SEMs), epigenetic age acceleration, and rare epivariations. Results: While no significant global methylation differences were observed between MDD cases and controls, hypomethylation near the SHF gene (brain-specific probe cg25801113) was consistently found in MDD cases. SEMs revealed a gene-level burden in MDD, though epigenetic age acceleration was not central to the disorder. Additionally, 51 rare epivariations were identified in blood tissue and 1 in brain tissue linked to MDD. Conclusions: The study emphasises the potential role of rare epivariations in MDD's epigenetic regulation but calls for further research with larger, more diverse cohorts to confirm these findings. [ABSTRACT FROM AUTHOR]

Abstract Background Major Depressive Disorder (MDD) is a leading cause of disability and results in excessive utilization of healthcare resources worldwide. The Middle East and North Africa (MENA) region shows a high prevalence of depressive disorders. Generalized Anxiety Disorder (GAD) and MDD have the highest rate of comorbidity of all mood and anxiety disorders, ranging from 40 to 98% in drug studies. Comorbid GAD results in more significant impairment in MDD and increases the severity of symptoms. Although several clinical trials supported the safety and effectiveness of vortioxetine, no data regarding these aspects has been revealed in the MENA region. This study aimed to assess the safety and efficacy of vortioxetine in patients with comorbid GAD in the United Arab Emirates (UAE). Method In a multicenter observational study, 118 patients with confirmed anxiety and depressive disorders were evaluated over four visits (baseline visit, two weeks, four weeks, and eight weeks) using MADRS and HAM-A scales to assess depression and anxiety severity, respectively by calculating mean change and the percent using Kendall’s W test. Results A significant mean difference in MADRS score was observed, with a gradual decrease of mean MADRS total scores over the assessment weeks (p

Abstract Utilizing waste materials to improve soil properties can result in cost savings and environmental benefits. This study aims to determine the effect of adding agricultural wastes like rice husk ash (RHA), rice husk (RH), and groundnut shells (GS) to clayey sands from Mysore district, India. The study focused on the undrained strength, permeability and volume change behaviour of soils mixed with RHA, RH and GS. The soil samples were mixed with varying amounts of RHA (5%, 10%, 15%, and 20%) and RH-GS (1%, 2%, 3%, 4%, and 5%) and cured for 1, 7, 14 and 21 days. These blended specimens were then used to determine the maximum dry density (MDD), optimum moisture content (OMC) and unconfined compressive strength (UCS). The soil mixture containing 5% RHA and 4% (RH + GS) yielded optimal results in the UCS test. Further tests, including unconsolidated undrained (UU) triaxial, permeability and consolidation tests, were conducted on the parent soil and the soil composite with 5% RHA and 4% (RH + GS). From the undrained test, the strength increased for the soil admixture, with a reduction in the cohesion and an increment in the friction angle, compared to that of the parent soil. The experimental results also showed improvement in the permeability and consolidation characteristics of the blended soil. As RH, GS, and RHA are abundant and considered to be agricultural waste products, using them represents an innovative, sustainable, and cost-effective solution with promising potential for soil improvement.

Understanding the multifactorial nature of major depressive disorder (MDD) is crucial for tailoring treatments. However, the complex interplay of various factors underlying the development and progression of MDD poses significant challenges. Our previous study demonstrated improvements in cognitive functions in MDD patients undergoing treatment with selective serotonin reuptake inhibitors (SSRIs) supplemented with Lactobacillus plantarum 299v (LP299v). To elucidate the biochemical mechanisms underlying cognitive functions improvements, we explored underlying metabolic changes. We employed multi-platform metabolomics, including LC-QTOF-MS and CE-TOF-MS profiling, alongside chiral LC-QqQ-MS analysis for amino acids. Supplementation of SSRI treatment with LP299v intensified the reduction of long-chain acylcarnitines, potentially indicating improved mitochondrial function. LP299v supplementation reduced N-acyl taurines more than four times compared to the placebo, suggesting a substantial impact on restoring biochemical balance. The LP299v -supplemented group showed increased levels of oxidized glycerophosphocholine (oxPC). Additionally, LP299v supplementation led to higher levels of sphingomyelins, L-histidine, D-valine, and p -cresol. This exploratory study suggests potential metabolic pathways influenced by LP299v supplementation. However, the need for further research hinders the ability to draw definitive conclusions. Observed metabolic changes were linked to mitochondrial dysfunction, inflammation, oxidative stress, and gut microbiota disruption. Despite the subtle nature of this alterations, our research successfully detected these differences and connected them to the metabolic disruptions associated with MDD. Our findings emphasise the intricate relationship between metabolism, gut microbiota, and mental health prompting further research into the mechanisms of action of probiotics in MDD treatment. [Display omitted] • Multi-platform metabolomics reveals intricate metabolism-gut-brain relationships. • Gender differences are noted in metabolic responses to LP299 v supplementation. • LP299v enhances SSRI effects, improving mitochondrial function. • LP299v significantly reduces N -acyl taurines. • LP299v increases sphingomyelins, L-histidine, D-valine, and p -cresol levels. [ABSTRACT FROM AUTHOR]

Cognitive impairment is common in major depressive disorder (MDD) and potentially linked to inflammation-induced alterations in brain function. However, the relationship between inflammation, dynamic brain activity, and cognitive impairment in MDD remains unclear. Fifty-seven first-episode, drug-naïve MDD patients and sixty healthy controls underwent fMRI scanning. Dynamic amplitude of low-frequency fluctuations (dALFF) and dynamic functional connectivity (dFC) were measured using the sliding window method. Plasma IL − 6 levels and cognitive function were assessed using enzyme-linked immunosorbent assay (ELISA) and the Repeated Battery for Assessment of Neuropsychological Status (RBANS), respectively. MDD patients exhibited decreased dALFF in the bilateral inferior temporal gyrus (ITG), right inferior frontal gyrus, opercular part (IFGoperc), and bilateral middle occipital gyrus (MOG). Regions of dALFF associated with IL-6 included right ITG (r = −0.400/ p = 0.003), left ITG (r = −0.381/ p = 0.004), right IFGoperc (r = −0.342/ p = 0.011), and right MOG (r = −0.327/ p = 0.016). Furthermore, IL-6-related abnormal dALFF (including right ITG: r = 0.309/ p = 0.023, left ITG: r = 0.276/ p = 0.044) was associated with attention impairment. These associations were absent entirely in MDD patients without suicidal ideation. Additionally, IL-6 levels were correlated with dFC of specific brain regions. Small sample size and cross-sectional study design. Inflammation-related dALFF was associated with attention impairment in MDD patients, with variations observed among MDD subgroups. These findings contribute to the understanding of the intricate relationship between inflammation, dynamic brain activity and cognitive impairments in MDD. • Plasma IL-6 levels were associated with abnormal dynamic brain activity in MDD patients. • IL-6-related abnormal dynamic brain activity was associated with cognition in MDD patients. • In MDD patients without suicidal ideation, the observed associations dissipated entirely. [ABSTRACT FROM AUTHOR]

Xiao-Meng Xie,1 Sha Sha,1 Hong Cai,2 Xinyu Liu,1 Isadora Jiang,3 Ling Zhang,1 Gang Wang1 1The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders Beijing Anding Hospital & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, School of Mental Health, Beijing, People’s Republic of China; 2Unit of Medical Psychology and Behavior Medicine, School of Public Health, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Bellarmine College of Liberal Arts, Loyola Marymount University, Los Angeles, CA, USACorrespondence: Gang Wang, Beijing Anding Hospital, Beijing, People’s Republic of China, Email gangwangdoc@gmail.comBackground: Major depressive disorder (MDD) becomes one of the psychiatric disorders characteristic of a combination of cognitive, emotional, and somatic symptoms. Additionally, cognitive impairment has the most significant impact on functional results. However, the evaluation of cognitive level is still based on various subjective questionnaires as there is no objective standard assessment yet. This research focuses on resting-state alpha activity to identify cognition in MDD patients using electroencephalography (EEG) signals.Methods: Ninety-two subjects were recruited: 44 patients with MDD and 48 healthy individuals as controls. Functional outcome and cognition were assessed using standardized instruments, and the EEG resting state signal of open and closed eyes was recorded. The comparison and correlation of cognitive levels with alpha power in the bilateral frontal region, bilateral central region, bilateral occipital region, and middle line was evaluated.Results: The relative alpha power in MDD group was significantly lower than that in the control group (P < 0.05). Through correlation analysis, it was shown that the bilateral frontal and occipital alpha power of MDD patients in the closed-eyes state was positively correlated with information processing rate, verbal learning, working memory, and attention retention. The alpha power of the bilateral frontal region in the open-eyes state was positively correlated with information processing rate, working memory, and attention retention (P < 0.05).Conclusion: The research indicates that the changes in frontal and occipital alpha activities may be a promising neurophysiological indicator of cognitive level to diagnose and treat response prediction.Keywords: major depressive disorder, MDD, EEG, alpha power, cognition impairment

Abstract Background General psychiatrists’ practice standards vary regarding when to implement transcranial magnetic stimulation (TMS) for care of patients with major depressive disorder (MDD). Furthermore, few studies have examined real-world utilization and clinical outcomes of TMS. This study analyzed data from a large, multi-site psychiatric practice to evaluate utilization and outcomes of TMS as well as usual care (UC) for patients with MDD. Methods Depression outcomes for TMS and UC among adult patients at a multi-site psychiatric group practice were examined in this retrospective cohort analysis. Patients with a primary diagnosis of MDD, PHQ-9 ≥ 10, and a visit in November 2020 with 6-month follow-up were included and categorized into the TMS or UC cohorts. Results Of 1,011 patients with qualifying PHQ-9 at the baseline visit, 9% (89) received a full course of TMS, and 583 patients receiving UC met study inclusion criteria (339 patients were excluded due to lacking a 6-month follow-up visit or receiving esketamine during the study period). The TMS cohort had higher baseline PHQ-9 than UC (17.9 vs. 15.5, p

Introduction: Proof-of-principle human studies suggest that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may improve depression severity. This open-label multicenter study tested remotely supervised multichannel tDCS delivered at home in patients (N=35) with major depressive disorder (MDD). The primary aim was to assess the feasibility and safety of our protocol. As an exploratory aim, we evaluated therapeutic efficacy: the primary efficacy measure was the median percent change from baseline to the end of the 4-week post-treatment follow-up period in the observer-rated Montgomery-Asberg Depression Mood Rating Scale (MADRS). Methods: Participants received 37 at-home stimulation sessions (30 minutes each) of specifically designed multichannel tDCS targeting the left DLPFC administered over eight weeks (4 weeks of daily treatments plus 4 weeks of taper), with a follow-up period of 4 weeks following the final stimulation session. The stimulation montage (electrode positions and currents) was optimized by employing computational models of the electric field generated by multichannel tDCS using available structural data from a similar population (group optimization). Conducted entirely remotely, the study employed the MADRS for assessment at baseline, at weeks 4 and 8 during treatment, and at 4-week follow-up visits. Results: 34 patients (85.3% women) with a mean age of 59 years, a diagnosis of MDD according to DSM-5 criteria, and a MADRS score ≥20 at the time of study enrolment completed all study visits. At baseline, the mean time since MDD diagnosis was 24.0 (SD 19.1) months. Concerning compliance, 85% of the participants (n=29) completed the complete course of 37 stimulation sessions at home, while 97% completed at least 36 sessions. No detrimental effects were observed, including suicidal ideation and/or behavior. The study observed a median MADRS score reduction of 64.5% (48.6, 72.4) 4 weeks post-treatment (Hedge's g = -3.1). We observed a response rate (≥ 50% improvement in MADRS scores) of 72.7% (n=24) from baseline to the last visit 4 weeks post-treatment. Secondary measures reflected similar improvements. Conclusions: These results suggest that remotely supervised and supported multichannel home-based tDCS is safe and feasible, and antidepressant efficacy motivates further appropriately controlled clinical studies. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT05205915?tab= results, identifier NCT05205915. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory disease that involves modified low-density lipoproteins (LDL) which play a pivotal role in the initiation and progression of the disease. Myeloperoxidase oxidized LDL (Mox-LDL) is considered to be the most patho-physiologically relevant type of modified LDL and has been reported to be ubiquitously present in atheroma plaques of patients with atherosclerosis. Besides its involvement in the latter disease state, Mox-LDL has also been shown to be implicated in the pathogenesis of various illnesses including sleep disorders, which are in turn associated with heart disease and depression in many intricate ways. Meanwhile, we have recently shown that lox-1-mediated Mox-LDL signaling modulates neuroserpin activity in endothelial cells, which could have major implications that go beyond the pathophysiology of stroke and cerebrovascular disease (CD). Of note is that tissue plasminogen activator (tPA), which is the main target of neuroserpin in the brain, has a crucial function in the processing of brain-derived neurotrophic factor (BDNF) into its mature form. This factor is known to be involved in major depressive disorder (MDD) development and pathogenesis. Since tPA is more conventionally recognized as being involved in fibrinolytic mechanisms, and its effect on the BDNF system in the context of MDD is still not extensively studied, we speculate that any Mox-LDL-driven change in the activity of tPA in patients with atherosclerosis may lead to a decrease in the production of mature BDNF, resulting in impaired neural plasticity and depression. Deciphering the mechanisms of interaction between those factors could help in better understanding the potentially overlapping pathological mechanisms that regulate disease processes in CD and MDD, supporting the possibility of novel and common therapeutic opportunities for millions of patients worldwide. [ABSTRACT FROM AUTHOR]

Introduction: Symptoms during the onset of major depressive disorder [MDD] and bipolar disorder type II [BD-II] are similar. The difference of hippocampus subregion could be a biological marker to distinguish MDD from BD-II. Methods: We recruited 61 drug-naïve patients with a first-episode MDD and BD-II episode and 30 healthy controls (HC) to participate in amagnetic resonance imaging [MRI] study. We built a general linear model (one-way analysis of covariance) with 22 hippocampal subfields and two total hippocampal volumes as dependent variables, and the diagnosis of MDD, BD-II, and HC as independent variables. We performed pair-wise comparisons of hippocampal subfield volumes between MDD and HC, BD-II and MDD, BD-II and HC with post hoc for primary analysis. Results: Weidentifiedthree regions that differed significantly in sizebetweenpatients and controls. The left hippocampal fissure, the hippocampal-amygdaloid transition area (HATA), and the right subiculum bodywere all significantly larger in patients with MDD compared with the HC. In the onset of first-episode of MDD, the hippocampal volume increased significantly, especially on the left side comparing toHC. However, we found differences between MDD and BD-II were not statistically significant. The volume of the left HATA and right subiculum body in BD-II was larger. Conclusions: The sample size of this study is relatively small, as it is a crosssectional comparative study. In both MDD and BD-II groups, the volume of more left subregions appeared to increase. The left subregions were severely injured in the development of depressive disorder. [ABSTRACT FROM AUTHOR]

Current pharmacological treatments for major depressive disorder (MDD) are often only partially effective, with many patients experiencing no significant benefit, leading to treatment-resistant depression (TRD). Psilocybin, a classical serotonergic psychedelic, has emerged as a notable emerging treatment for such disorders. The aim of this systematic review and meta-analysis is to summarize and discuss the most recent evidence about the therapeutic effects of single-dose and two-dose psilocybin administration on the severity of depressive symptoms, as well as compare the efficacy of these interventions among patients with a primary diagnosis of MDD or TRD. Articles were collected from EBSCOhost and PubMed following the PRISMA guidelines, yielding 425 articles with 138 duplicates. After screening 287 records, 12 studies met the eligibility criteria and were included in the review. A quantitative analysis of the studies indicates that psilocybin is highly effective in reducing depressive symptoms severity among patients with primary MDD or TRD. Both single-dose and two-dose psilocybin treatments significantly reduced depressive symptoms severity, with two-dose administration sometimes yielding more pronounced and lasting effects. However, it is unclear if this was solely due to dosage or other factors. Future research should include standardized trials comparing these dosing strategies to better inform clinical practice. [ABSTRACT FROM AUTHOR]

Unipolar depression is a prevalent and disabling condition, often left untreated. In the outpatient setting, general practitioners fail to recognize depression in about 50% of cases mainly due to somatic comorbidities. Given the significant economic, social, and interpersonal impact of depression and its increasing prevalence, there is a need to improve its diagnosis and treatment in outpatient care. Various efforts have been made to isolate individual biological markers for depression to streamline diagnostic and therapeutic approaches. However, the intricate and dynamic interplay between neuroinflammation, metabolic abnormalities, and relevant neurobiological correlates of depression is not yet fully understood. To address this issue, we propose a naturalistic prospective study involving outpatients with unipolar depression, individuals without depression or comorbidities, and healthy controls. In addition to clinical assessments, cardiovascular parameters, metabolic factors, and inflammatory parameters are collected. For analysis we will use conventional statistics as well as machine learning algorithms. We aim to detect relevant participant subgroups by data-driven cluster algorithms and their impact on the subjects' long-term prognosis. The POKAL-PSY study is a subproject of the research network POKAL (Predictors and Clinical Outcomes in Depressive Disorders; GRK 2621). [ABSTRACT FROM AUTHOR]

Introduction: The Global Psychotrauma Screen (GPS) is a brief transdiagnostic screener that covers a broad range of trauma-related disorders as well as risk factors known to influence the course of symptoms. Methods: We analyzed data from African war refugees in Australia (n = 70), including the GPS, the Structured Clinical Interview for DSM-5 Disorders (SCID-5), the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), and the Brief Resilience Scale (BRS). Results: Using the Youden's J Index to examine the clinical validity of the GPS subscales measuring PTSD, dissociation, depression, and generalized anxiety disorder (GAD), we found that a PTSD subscale score of 3 or higher, and a depression and dissociation subscale score of 1 or higher, was optimally efficient for detecting a probable diagnosis (Youden's J = 0.76, J = 0.72, and J = 0.90, respectively) with high sensitivity and specificity. We were unable to test the GPS clinical validity for GAD due to the low GAD occurrence. The GPS resilience item was not related to the total score (r = 0.02), indicating low convergent validity for resilience. Risk factors, including current stressors and childhood trauma history, were related to more severe GPS symptom scores, while lack of resilience, social support, and history of mental illness were not. Conclusion: We conclude that the GPS may be a useful screening tool for PTSD, depression, and the dissociative subtype in refugees. [ABSTRACT FROM AUTHOR]

The utilization of non-invasive neurostimulation techniques, such as transcranial magnetic stimulation (TMS), is increasingly prevalent in psychiatry due to their efficacy and safety. Although the precise therapeutic mechanisms remain partially unclear, repetitive TMS, particularly high-frequency stimulation, may enhance cognitive functions, contributing to therapeutic benefits. This within-subjects study examined the impact of TMS on cognitive and symptomatic outcomes in patients with obsessive–compulsive disorder (OCD), substance use disorder (SUD), and major depressive disorder (MDD). A total of 44 patients underwent cognitive tests and symptom assessments before and after an intensive four-week TMS treatment phase, followed by a four-week maintenance phase. Cognitive assessments included Raven's matrices, verbal fluency, and digit span tests, while symptom severity was measured using the Italian version of the SCL-90-R. Decision-making performance was also evaluated by administering a delay discounting (DD) test. Principal component analysis was used to generate a dimensional characterization of subjects along cognitive and symptom-related axes before and after treatment. The results indicated that TMS significantly improved symptom scores, but no significant cognitive enhancement was observed. Statistical analysis based on linear mixed-effects models confirmed these findings, showing a significant fixed effect of TMS treatment on symptoms but not on cognitive performance. DD metrics remained unchanged. These findings suggest that while TMS effectively alleviates clinical symptoms, it does not produce consistent or appreciable enhancement of cognitive functions in these protocols. This study highlights the need for more personalized and combined therapeutic approaches to maximize the benefits of TMS, potentially incorporating cognitive enhancement strategies. Future studies will be useful to explore whether the results we obtained are valid for other pathologies, cognitive tests, and stimulation protocols. [ABSTRACT FROM AUTHOR]

Background: General psychiatrists' practice standards vary regarding when to implement transcranial magnetic stimulation (TMS) for care of patients with major depressive disorder (MDD). Furthermore, few studies have examined real-world utilization and clinical outcomes of TMS. This study analyzed data from a large, multi-site psychiatric practice to evaluate utilization and outcomes of TMS as well as usual care (UC) for patients with MDD. Methods: Depression outcomes for TMS and UC among adult patients at a multi-site psychiatric group practice were examined in this retrospective cohort analysis. Patients with a primary diagnosis of MDD, PHQ-9 ≥ 10, and a visit in November 2020 with 6-month follow-up were included and categorized into the TMS or UC cohorts. Results: Of 1,011 patients with qualifying PHQ-9 at the baseline visit, 9% (89) received a full course of TMS, and 583 patients receiving UC met study inclusion criteria (339 patients were excluded due to lacking a 6-month follow-up visit or receiving esketamine during the study period). The TMS cohort had higher baseline PHQ-9 than UC (17.9 vs. 15.5, p <.001) and had failed more medication trials (≥ 4 vs. 3.1, p <.001). Mean PHQ-9 decreased by 5.7 points (SD = 6.7, p <.001) in the TMS cohort and by 4.2 points (SD = 6.4, p <.001) in the UC cohort over the study period. Among patients who had failed four or more antidepressant medications, PHQ-9 decreased by 5.8 points in the TMS cohort (SD = 6.7, p <.001) and by 3.2 points in the UC cohort (SD = 6.3, p <.001). Conclusions: TMS utilization was low, despite TMS showing significant real-world clinical benefits. Future research should examine and address barriers to wider adoption of TMS into routine patient care for patients with treatment-resistant MDD. Wider adoption including routine use of TMS in less treatment-resistant patients will allow statistical comparisons of outcomes between TMS and UC populations that are difficult to do when TMS is underutilized. [ABSTRACT FROM AUTHOR]

Background Evidence indicates an association between immune dysregulation and major depressive disorder (MDD). Pentoxifylline (PTX), a phosphodiesterase inhibitor, has been shown to reduce pro-inflammatory activities. The aim of this study was to evaluate changes in depressive symptoms and pro-inflammatory markers after administration of PTX as an adjunctive agent to citalopram in patients with MDD. Methods One hundred patients were randomly assigned to either citalopram (20 mg/day) plus placebo (twice daily) (n=50) or citalopram (20 mg/day) plus PTX (400 mg) (twice daily) (n=50). The Hamilton Depression Rating Scale-17 (HAM-D-17) scores at baseline, weeks 2, 4, 6, 8, 10, and 12 and serum levels of interleukin1-β (IL-1-β), tumor necrosis factor-α, C-reactive protein, IL-6, serotonin, IL-10, and brain-derived neurotrophic factor (BDNF) at baseline and week 12 were evaluated. Results HAM-D-17 score in the PTX group significantly reduced in comparison to the control group after weeks 4, 6, 8,10, and 12 ((LSMD): − 2.193, p=0.021; − 2.597, p=0.036; − 2.916, p=0.019; − 4.336, p=0.005; and − 4.087, p=0.008, respectively). Patients who received PTX had a better response (83%) and remission rate (79%) compared to the placebo group (49% and 40%, p=0.006 and p=0.01, respectively). Moreover, the reduction in serum concentrations of pro-inflammatory factors and increase in serotonin and BDNF in the PTX group was significantly greater than in the placebo group (p<0.001). Conclusion These findings support the safety and efficacy of PTX as an adjunctive antidepressant agent with anti-inflammatory effects in patients with MDD. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is a leading cause of disability worldwide, as it can lead to cognitive and functional impairment and premature mortality. The first episode of BD is usually a depressive episode and is often misdiagnosed as major depressive disorder (MDD). Growing evidence indicates that peripheral immune activation and inflammation are involved in the pathophysiology of BD and MDD. Recently, by developing a panel of RNA editing-based blood biomarkers able to discriminate MDD from depressive BD, we have provided clinicians a new tool to reduce the misdiagnosis delay observed in patients suffering from BD. The present study aimed at validating the diagnostic value of this panel in an external independent multicentric Switzerland-based cohort of 143 patients suffering from moderate to major depression. The RNA-editing based blood biomarker (BMK) algorithm developped allowed to accurately discriminate MDD from depressive BD in an external cohort, with high accuracy, sensitivity and specificity values (82.5 %, 86.4 % and 80.8 %, respectively). These findings further confirm the important role of RNA editing in the physiopathology of mental disorders and emphasize the possible clinical usefulness of the biomarker panel for optimization treatment delay in patients suffering from BD. • The differential diagnosis of BD and MDD is challenging leading to a long delay in BD characterisation • RNA editing is an early regulatory system whose modifications are involved in psychiatric disorders like BD and MDD. • RNA editing related blood biomarkers are identified in patients with mood disorders • AI algorithm using RNA editing biomarkers will discriminate depressed BD from MDD and validated in two independant cohorts. [ABSTRACT FROM AUTHOR]

This study aims to achieve the densest possible state of soil for constructing dams and roads. This requires assessing the compaction characteristics, Optimum Moisture Content (OMC), and Maximum Dry Density (MDD) to determine the soil's suitability for earthworks. However, this process is resource-intensive and time-consuming. To streamline the assessment, the study incorporates six parameters: gravel (G), sand (S), fine (F) contents, plastic limit (PL), liquid limit (LL), and plasticity index (PI). Four different models are used to predict compaction characteristics: artificial neural network (ANN), nonlinear regression (NLR), linear regression (LR), and multilinear regression (MLR). The study utilized a substantial dataset of 2162 entries, considering various soil gradation and plasticity properties as input variables. To evaluate the models' effectiveness, several statistical measures, including coefficient of determination (R2), scatter index (SI), root mean squared error (RMSE), mean absolute error (MAE), a20-index, and Objective (OBJ) value, were employed. The ANN model outperformed other models in predicting OMC, with RMSE, MAE, OBJ, SI, a20-index, and R2 values of 3.51, 2.31, 4.26, 0.202, 0.7, and 0.92%, respectively. However, for predicting MDD, the ANN model had the highest R2 value (R2 = 0.87), but the minimum RMSE (1.01), MAE (0.8), a20-index (0.998), and OBJ (1.07) were obtained from the MLR and LR models. Furthermore, sensitivity analyses revealed that the plastic limit significantly influences the OMC, while the gravel content plays a dominant role in predicting MDD. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) are often underpowered due to small effect sizes of common single nucleotide polymorphisms (SNPs) on phenotypes and extreme multiple testing thresholds. The most common approach for increasing statistical power is to increase sample size. We propose an alternative strategy of redefining case-control outcomes into ordinal case-subthreshold-asymptomatic variables. While maintaining the clinical case threshold, we subdivide controls into two groups: individuals who are symptomatic but do not meet the clinical criteria for diagnosis (subthreshold) and individuals who are effectively asymptomatic. We conducted a simulation study to examine the impact of effect size, minor allele frequency, population prevalence, and the prevalence of the subthreshold group on statistical power to detect genetic associations in three scenarios: a standard case-control, an ordinal, and a case-asymptomatic control analysis. Our results suggest the ordinal model consistently provides the greatest statistical power while the case-control model the least. Power in the case-asymptomatic control model reflects the case-control or ordinal model depending on the population prevalence and size of the subthreshold category. We then analyzed a major depression phenotype from the UK Biobank to corroborate our simulation results. Overall, the ordinal model improves statistical power in GWAS consistent with increasing the sample size by approximately 10%. [ABSTRACT FROM AUTHOR]

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Background: To investigate the association between pre-trial expectancy, suggestibility, and response to treatment in a trial of escitalopram and investigational drug, COMP360, psilocybin, in the treatment of major depressive disorder (ClinicalTrials.gov registration: NCT03429075). Methods: We used data (n = 55) from our recent double-blind, parallel-group, randomized head-to-head comparison trial of escitalopram and investigational drug, COMP360, psilocybin. Mixed linear models were used to investigate the association between pre-treatment efficacy-related expectations, as well as baseline trait suggestibility and absorption, and therapeutic response to both escitalopram and COMP360 psilocybin. Results: Patients had significantly higher expectancy for psilocybin relative to escitalopram; however, expectancy for escitalopram was associated with improved therapeutic outcomes to escitalopram, expectancy for psilocybin was not predictive of response to psilocybin. Separately, we found that pre-treatment trait suggestibility was associated with therapeutic response in the psilocybin arm, but not in the escitalopram arm. Conclusions: Overall, our results suggest that psychedelic therapy may be less vulnerable to expectancy biases than previously suspected. The relationship between baseline trait suggestibility and response to psilocybin therapy implies that highly suggestible individuals may be primed for response to this treatment. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a severe psychiatric illness known to be highly complex due to its difficulty in identifying genetic factors and its polygenic nature. While genetic studies and research into epigenetic changes have advanced our understanding of MDD, the precise role of genetics in MDD's manifestation remains elusive. This paper reviews the current state of research on MDD genetics, encompassing findings on MDD's biological blueprint and investigations into epigenetic modifications associated with MDD development. Furthermore, this paper explores the interplay between depression and the immune system and the impact of inflammation on the disorder. Neuroimaging studies have also impacted comprehension of MDD, revealing alterations in brain size and chemistry. These insights shed light on the biological underpinnings of MDD and hold promise for developing more effective treatments and therapies for patients. [ABSTRACT FROM AUTHOR]

Abstract Introduction Major Depressive Disorder (MDD) is one of the commonest mental disorders affecting more than 250 million people globally. Patients with chronic illnesses had higher risks for developing MDD than the general population. Neurolathyrism is a chronic illness characterized by lifelong incurable spastic paralysis of lower extremities; causing permanent disability. It is highly prevalent in Dawunt district, Ethiopia; with a point prevalence of 2.4%. Despite this, there were no previous studies assessing the prevalence of MDD among patients with neurolathyrism in Ethiopia. Objective To assess the prevalence of MDD and to identify its associated factors among patients with neurolathyrism in Dawunt district, Ethiopia. Methods A community based cross-sectional study was conducted on 260 samples in Dawunt district from February 01 to March 30/ 2021. Multistage sampling technique was used to select study participants. The patient Health Questionnaire-9 (PHQ-9) depression screening tool was used to diagnose MDD. PHQ-9 is a standardized depression screening tool and a PHQ-9 score of ≥ 10 has a sensitivity and specificity of 88.0% [95% CI (83.0–92.0%)] and 85.0% [95% CI (82.0–88.0%)] for screening MDD. Data were collected by interview; entered to EpiData version 4.2.0; exported to SPSS version 25.0 for analysis; descriptive statistics and binary logistic regression model were used; AOR with 95% CI was used to interpret the associations; and finally results were presented by texts, charts, graphs, and tables. Results A total of 256 adult patients with neurolathyrism were participated; and the prevalence of MDD was found to be 38.7%. Being female [AOR = 3.00; 95% CI (1.15, 7.84)], living alone [AOR = 2.77; 95% CI (1.02–7.53)], being on neurolathyrism stage-3 [AOR = 3.22; 95% CI (1.09, 9.54)] or stage-4 [AOR = 4.00; 95% CI (1.28, 12.48)], stigma [AOR = 2.69; 95% CI (1.34, 5.39)], and lack of social/ family support [AOR = 3.61; 95% CI (1.80, 7.24)] were found to have statistically significant association with an increased odds of MDD; while regular exercise and ever formal counselling were found to have statistically significant association with a decreased odds of MDD. Conclusion The prevalence of MDD among neurolathyrism patients in Dawunt district was high. Lack of social support, stigma, not getting formal counselling, and not involving in regular exercise were modifiable risk factors. Therefore, social support, reducing stigma, formal counselling, and encouraging regular exercise might help to reduce the burden of MDD among neurolathyrism patients.

Introduction: The prevalence of major depressive disorder (MDD) increased during the COVID-19 pandemic. Data on suicidality in these patients during the pandemic period remain scarce. The aim of the study was to determine the prevalence and variables associated with serious suicide risk in Russian inpatients with MDD during the COVID-19 pandemic. Methods: A cross-sectional cohort study with consecutive sampling was conducted from January 1, 2021 to December 31, 2021. All patients completed the Mini International Neuropsychiatric Interview (M.I.N.I.) (including the suicidality module), the Beck Depression Inventory, and the State-Trait Anxiety Inventory, and underwent a semi-structured interview to collect relevant demographic and clinical data. Effect sizes for all independent variables and covariates were calculated using partial eta-squared (hp2). Results: Of the 6757 patients with non-psychotic mental disorders assessed, 1605 (23.7%) had MDD confirmed by the M.I.N.I., of whom 17.8% were at serious risk for suicide according to theM.I.N.I. suicidality module. Factors independently associated with serious suicide risk in Russian inpatients with MDD during the pandemic were younger age (hp2 = 0.021), greater severity of depression (0.038), higher state anxiety (0.003), and nonsuicidal self-injury (NSSI) (0.066). The same variables, except for state anxiety, were independently associated with suicide risk in the subgroup of MDD patients previously infected with SARS-CoV2. Conclusion: In the COVID-19 pandemic, the proportion of patients with MDD at serious risk of suicide was similar to pre-pandemic data. No associations were found between suicidality in patients with MDD and COVID-related factors. Younger age, greater severity of depression, and especially NSSI were the most significant risk factors for suicide in patients with MDD during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Event centrality is defined by the extent to which a memory of an event has become central to an individual's identity and life story. Previous research predominantly focused on the link between event centrality and trauma-related symptomatology. Nevertheless, it can be argued that the perception of (adverse) events as central to one's self is not exclusive to Posttraumatic Stress Disorder (PTSD). Other disorders where adverse events are linked to the onset of symptoms might also be related to event centrality. This study examined the relevance of event centrality for Social Anxiety Disorder (SAD) and for Major Depressive Disorder (MDD) separately. Moreover, we examined which cognitive and emotion regulation variables (i.e., trait anxiety, rumination, worry, intrusions and avoidance, and posttraumatic cognitions) mediated these relationships. No significant correlation was found between event centrality and social anxiety. However, a significant positive correlation was found between event centrality and depression. In a combined group, this relation was mediated by all cognitive and emotion regulation variables except for worry. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cerebral examination via CTA is always the first choice for patients with unexpected brain injury or different types of brain lesions to detect ruptured hemangiomas, vascular infarcts, or other brain tissue lesions. OBJECTIVE: This study innovated the acrylic gauge with five eccentric circles for computed tomography angiography (CTA) analysis to optimize the spatial resolution via Taguchi's methodology. METHODS: The customized gauge was revised from the V-shaped slit gauge and transferred into five eccentric circles' slit gauge. The gauge was assembled with another six acrylic layers to simulate the human head. Taguchi's L18 orthogonal array was adopted to optimize the spatial resolution of CTA imaging quality. In doing so, six essential factors of CTA are kVp, mAs, spiral rotation pitch, FOV, rotation time of the CT and reconstruction filter, and each factor has either two or three levels to organize into eighteen combinations to simulate the full factor combination of 486 (21 × 35 = 486) times according to Taguchi's recommendation. Three well-trained radiologists ranked the gauge's 18 CTA scanned imaging qualities according to contrast, sharpness, and spatial resolution and derived the unique fish-bone-plot of six factors for further analysis. The optimal factor combination of CTA was proven by follow-up verification and ANOVA to obtain this study's dominant or minor factor. RESULTS: The optimal factor combination of CTA was A2 (120 kVp), B3 (200 mAs), C1 (Pitch 0.6), D2 (FOV 220 mm2), E1 (rotation time 0.33 s), and F3 (Brain sharp, UC). Furthermore, deriving a quantified MDD (minimum detectable difference) to imply the spatial resolution of CTA, a semiauto profile analysis program run in MATLAB and OriginPro was recommended to evaluate the MDD and to suppress the manual error in calculation. Eventually, the derived MDDs of the conventional and optimal factor combinations of CTA were 2.35 and 2.26 mm, respectively, in this study. CONCLUSION: Taguchi's methodology was found applicable for quantifying the CTA imaging quality in practical applications. [ABSTRACT FROM AUTHOR]

Introduction: Major Depressive Disorder (MDD) is one of the commonest mental disorders affecting more than 250 million people globally. Patients with chronic illnesses had higher risks for developing MDD than the general population. Neurolathyrism is a chronic illness characterized by lifelong incurable spastic paralysis of lower extremities; causing permanent disability. It is highly prevalent in Dawunt district, Ethiopia; with a point prevalence of 2.4%. Despite this, there were no previous studies assessing the prevalence of MDD among patients with neurolathyrism in Ethiopia. Objective: To assess the prevalence of MDD and to identify its associated factors among patients with neurolathyrism in Dawunt district, Ethiopia. Methods: A community based cross-sectional study was conducted on 260 samples in Dawunt district from February 01 to March 30/ 2021. Multistage sampling technique was used to select study participants. The patient Health Questionnaire-9 (PHQ-9) depression screening tool was used to diagnose MDD. PHQ-9 is a standardized depression screening tool and a PHQ-9 score of ≥ 10 has a sensitivity and specificity of 88.0% [95% CI (83.0–92.0%)] and 85.0% [95% CI (82.0–88.0%)] for screening MDD. Data were collected by interview; entered to EpiData version 4.2.0; exported to SPSS version 25.0 for analysis; descriptive statistics and binary logistic regression model were used; AOR with 95% CI was used to interpret the associations; and finally results were presented by texts, charts, graphs, and tables. Results: A total of 256 adult patients with neurolathyrism were participated; and the prevalence of MDD was found to be 38.7%. Being female [AOR = 3.00; 95% CI (1.15, 7.84)], living alone [AOR = 2.77; 95% CI (1.02–7.53)], being on neurolathyrism stage-3 [AOR = 3.22; 95% CI (1.09, 9.54)] or stage-4 [AOR = 4.00; 95% CI (1.28, 12.48)], stigma [AOR = 2.69; 95% CI (1.34, 5.39)], and lack of social/ family support [AOR = 3.61; 95% CI (1.80, 7.24)] were found to have statistically significant association with an increased odds of MDD; while regular exercise and ever formal counselling were found to have statistically significant association with a decreased odds of MDD. Conclusion: The prevalence of MDD among neurolathyrism patients in Dawunt district was high. Lack of social support, stigma, not getting formal counselling, and not involving in regular exercise were modifiable risk factors. Therefore, social support, reducing stigma, formal counselling, and encouraging regular exercise might help to reduce the burden of MDD among neurolathyrism patients. [ABSTRACT FROM AUTHOR]

Blunted motivation is a core symptom of Major Depressive Disorder (MDD). Although the empirical picture is mixed, cognitive processes that can be collectively referred to as reward processing have been found to be consistently muted in MDD; most notably, reward sensitivity and reinforcement learning. Works on the modulation of response vigor in individuals with MDD have examined various types of reward, but recent research has shown that in the general population, response vigor is not modulated by type of reward on tasks that are highly similar to those used in these experiments. The present study implemented a form of non-reward related reinforcement which has repeatedly been shown to modulate response vigor in the general population. It investigated whether modulation of response vigor by this type of reinforcement would be effective in individuals with MDD. Clinically depressed individuals (N = 121; 76 post-exclusion) engaged in a task in which their responses led to predictable and immediate sensorimotor effects, or no such effects. Response vigor increased when responses led to sensorimotor effects, which was comparable to the increase found in the general population. These findings support the utility of isolating the computations leading to different reinforcement types and suggest that motivational deficits in MDD may be specific to the type of reward (i.e., hedonically or otherwise explicitly desired stimuli). These results contribute to the literature by suggesting that the reinforcement from sensorimotor predictability stems from processes devolved to motor control, whereas reinforcement from rewards may depend on more general-purpose processes. [ABSTRACT FROM AUTHOR]

Psychiatric disorders represent a primary source of disability worldwide, manifesting as disturbances in individuals' cognitive processes, emotional regulation, and behavioral patterns. In the quest to discover novel therapies and expand the boundaries of neuropharmacology, studies from the field have highlighted the gut microbiota's role in modulating these disorders. These alterations may influence the brain's processes through the brain–gut axis, a multifaceted bidirectional system that establishes a connection between the enteric and central nervous systems. Thus, probiotic and prebiotic supplements that are meant to influence overall gut health may play an insightful role in alleviating psychiatric symptoms, such as the cognitive templates of major depressive disorder, anxiety, or schizophrenia. Moreover, the administration of psychotropic drugs has been revealed to induce specific changes in a microbiome's diversity, suggesting their potential utility in combating bacterial infections. This review emphasizes the intricate correlations between psychiatric disorders and the gut microbiota, mentioning the promising approaches in regard to the modulation of probiotic and prebiotic treatments, as well as the antimicrobial effects of psychotropic medication. [ABSTRACT FROM AUTHOR]

Due to the high comorbidity of Parkinson's disease (PD) with major depressive disorder (MDD) and the involvement of sphingolipids in both conditions, we investigated the peripheral expression levels of three primarily PD-associated genes: α-synuclein (SNCA), lysosomal enzyme β-glucocerebrosidase (GBA1), and UDP-glucose ceramide glucosyltransferase (UGCG) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated n = 63, medicated n = 66) and controls (remitted MDD n = 39, healthy subjects n = 61). We observed that expression levels of SNCA (p = 0.036), GBA1 (p = 0.014), and UGCG (p = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of GBA1 and UGCG decreased in medicated patients during three weeks of therapy. Additionally, in subgroups, expression was positively correlated with the severity of depression and anxiety. Furthermore, we identified correlations between the gene expression levels and PD-related laboratory parameters. Our findings suggest that SNCA, GBA1, and UGCG analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases. [ABSTRACT FROM AUTHOR]

Theta burst stimulation (TBS) is a noninvasive brain stimulation technique that can be used to modulate neural networks underlying psychiatric and neurological disorders. TBS can be delivered intermittently or continuously. The conventional intermittent TBS protocol is approved by the U.S. Food and Drug Administration to treat otherwise treatment-resistant depression, but the 6-week duration limits the applicability of this therapy. Accelerated TBS protocols present an opportunity to deliver higher pulse doses in shorter periods of time, thus resulting in faster and potentially more clinically effective treatment. However, the acceleration of TBS delivery raises questions regarding the relative safety, efficacy, and durability compared with conventional TBS protocols. In this review paper, we present the data from accelerated TBS trials to date that support the safety and effectiveness of accelerated protocols while acknowledging the need for more durability data. We discuss the stimulation parameters that seem to be important for the efficacy of accelerated TBS protocols and possible avenues for further optimization. [ABSTRACT FROM AUTHOR]

IntroductionProof-of-principle human studies suggest that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may improve depression severity. This open-label multicenter study tested remotely supervised multichannel tDCS delivered at home in patients (N=35) with major depressive disorder (MDD). The primary aim was to assess the feasibility and safety of our protocol. As an exploratory aim, we evaluated therapeutic efficacy: the primary efficacy measure was the median percent change from baseline to the end of the 4-week post-treatment follow-up period in the observer-rated Montgomery-Asberg Depression Mood Rating Scale (MADRS).MethodsParticipants received 37 at-home stimulation sessions (30 minutes each) of specifically designed multichannel tDCS targeting the left DLPFC administered over eight weeks (4 weeks of daily treatments plus 4 weeks of taper), with a follow-up period of 4 weeks following the final stimulation session. The stimulation montage (electrode positions and currents) was optimized by employing computational models of the electric field generated by multichannel tDCS using available structural data from a similar population (group optimization). Conducted entirely remotely, the study employed the MADRS for assessment at baseline, at weeks 4 and 8 during treatment, and at 4-week follow-up visits.Results34 patients (85.3% women) with a mean age of 59 years, a diagnosis of MDD according to DSM-5 criteria, and a MADRS score ≥20 at the time of study enrolment completed all study visits. At baseline, the mean time since MDD diagnosis was 24.0 (SD 19.1) months. Concerning compliance, 85% of the participants (n=29) completed the complete course of 37 stimulation sessions at home, while 97% completed at least 36 sessions. No detrimental effects were observed, including suicidal ideation and/or behavior. The study observed a median MADRS score reduction of 64.5% (48.6, 72.4) 4 weeks post-treatment (Hedge’s g = -3.1). We observed a response rate (≥ 50% improvement in MADRS scores) of 72.7% (n=24) from baseline to the last visit 4 weeks post-treatment. Secondary measures reflected similar improvements.ConclusionsThese results suggest that remotely supervised and supported multichannel home-based tDCS is safe and feasible, and antidepressant efficacy motivates further appropriately controlled clinical studies.Clinical Trial Registrationhttps://clinicaltrials.gov/study/NCT05205915?tab=results, identifier NCT05205915.

IntroductionThe Global Psychotrauma Screen (GPS) is a brief transdiagnostic screener that covers a broad range of trauma-related disorders as well as risk factors known to influence the course of symptoms.MethodsWe analyzed data from African war refugees in Australia (n = 70), including the GPS, the Structured Clinical Interview for DSM-5 Disorders (SCID-5), the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), and the Brief Resilience Scale (BRS).ResultsUsing the Youden’s J Index to examine the clinical validity of the GPS subscales measuring PTSD, dissociation, depression, and generalized anxiety disorder (GAD), we found that a PTSD subscale score of 3 or higher, and a depression and dissociation subscale score of 1 or higher, was optimally efficient for detecting a probable diagnosis (Youden’s J = 0.76, J = 0.72, and J = 0.90, respectively) with high sensitivity and specificity. We were unable to test the GPS clinical validity for GAD due to the low GAD occurrence. The GPS resilience item was not related to the total score (r = 0.02), indicating low convergent validity for resilience. Risk factors, including current stressors and childhood trauma history, were related to more severe GPS symptom scores, while lack of resilience, social support, and history of mental illness were not.ConclusionWe conclude that the GPS may be a useful screening tool for PTSD, depression, and the dissociative subtype in refugees.