[Anxiety-depressive disorders in patients before and in the long terms after aortic replacement]. / Trevozhno-depressivnye rasstroistva u patsientov do i v otdalennye sroki posle protezirovaniya aorty.

OBJECTIVE: To study the structure and dynamics of anxiety-depressive disorders in patients with dissection/aneurysm of the ascending aorta and aortic arch before and in the long term after surgical treatment and to identify factors associated with disturbances in psycho-emotional status. MATERIAL AND METHODS: We examined 124 patients with dissection/aneurysm of the ascending aorta and arch before and in the long-term period after aortic replacement, assessing anxiety and depression using the Generalized Anxiety Disorder (GAD-7) and Beck Depression Questionnaires. Multivariate regression analysis was used to identify factors associated with clinically significant anxiety and depressive disorders. RESULTS: Average scores on the GAD and the depression scale before surgery decreased from 6.5 (4.0-9.0) and 12.0 (8.0-16.0) to 3.0 (2.0-5.0) and 6.0 (3.0-10.0) (p<0.05) respectively, in the long-term postoperative period. There was no significant decrease in the proportion of patients with clinically significant levels of GAD and depression (p>0.05). Before surgery, clinically significant anxiety and depressive disorders are associated with older age, chronic cerebrovascular insufficiency (CCI) and atrial fibrillation (AF) in the hospital period. After surgery, clinically significant GAD was associated with older age, CCI, and a history of stroke. Depressive disorders were associated with older age and a history of stroke. CONCLUSION: In all patients with aortic disease, GAD and depression of varying severity are recorded; clinically significant GAD and depression are recorded in 19.2 and 23.2% of cases. In the long-term postoperative period, there is no significant decrease in the proportion of patients with clinically significant levels of GAD and depression, which amounted to 10.1 and 13.1%. Clinically significant anxiety and depressive disorders before and after surgery are associated with older age and the history of cerebrovascular disorders. In addition, the baseline clinically significant anxiety and depressive disorders showed an association with the subsequent development of AF in the early postoperative period.

Sleep quality and the cortisol and alpha-amylase awakening responses in adolescents with depressive disorders.

BACKGROUND: Depressive disorders in adolescents affect all aspects of life and impose a very large burden of disease. Sleep is frequently affected by depression and is crucial for facing challenges during development. One of the postulated reasons for depression-induced sleep disruption is dysregulation of the physiological stress system. AIMS: To investigate the links of adolescent depressive disorders with subjective sleep quality, objective sleep quality, and the course of cortisol and alpha-amylase after awakening. METHOD: We compared subjective sleep quality (via daily questionnaires) and objective sleep quality (via actigraphy measurement) of 35 adolescents with depressive disorders and 29 healthy controls over 7 consecutive days. In addition, saliva samples were collected on 3 days to examine cortisol and alpha-amylase patterns after awakening. RESULTS: No significant differences in cortisol or alpha-amylase awakening responses were observed between participants with depressive disorders and healthy controls. We found severe reductions in subjective sleep quality in the depression group (Z = -5.19, P < 0.001, d = 1.80) and a prolonged actigraphy-measured sleep onset latency (Z = -2.42, P = 0.015, d = 0.64) compared with controls. Reductions in subjective sleep quality were partially correlated with objective sleep measures (sleep onset latency: r = -0.270, P = 0.004, sleep efficiency: r = 0.215, P = 0.017). CONCLUSIONS: Sleep onset latency seems to aggravate depressive symptoms and to have an important role in perception of sleep quality. Adolescents with depressive disorders should be supported regarding the establishment of good sleep hygiene and avoiding activities that may impede falling asleep.

Perspectives on physician-assisted suicide in mental healthcare: results of a survey of physicians and medical students.

BACKGROUND: Physician-assisted suicide (PAS) is typically associated with serious physical illnesses that are prevalent in palliative care. However, individuals with mental illnesses may also experience such severity that life becomes intolerable. In February 2020, the previous German law prohibiting PAS was repealed. Patients with severe mental illnesses are increasingly likely to approach physicians with requests for PAS. AIMS: To explore the ethical and moral perspectives of medical students and physicians when making individual decisions regarding PAS. METHOD: An anonymised digital survey was conducted among medical students and physicians in Germany. Participants were presented with a case vignette of a chronically depressed patient requesting PAS. Participants decided on PAS provision and assessed theoretical arguments. We employed generalised ordinal regression and qualitative analysis for data interpretation. RESULTS: A total of N = 1478 participants completed the survey. Of these, n = 470 (32%) stated that they would refuse the request, whereas n = 582 (39%) would probably refuse, n = 375 (25%) would probably agree and n = 57 (4%) would definitely agree. Patient-centred arguments such as the right to self-determination increased the likelihood of consent. Concerns that PAS for chronically depressed patients might erode trust in the medical profession resulted in a decreased willingness to provide PAS. CONCLUSIONS: Participants displayed relatively low willingness to consider PAS in the case of a chronically depressed patient. This study highlights the substantial influence of theoretical medical-ethical arguments and the broader public discourse, underscoring the necessity of an ethical discussion on PAS for mental illnesses.

rTMS as a Next Step in Antidepressant Nonresponders: A Randomized Comparison With Current Antidepressant Treatment Approaches.

OBJECTIVE: Although repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, little is known about the comparative effectiveness of rTMS and other treatment options, such as antidepressants. In this multicenter randomized controlled trial, rTMS was compared with the next pharmacological treatment step in patients with treatment-resistant depression. METHODS: Patients with unipolar nonpsychotic depression (N=89) with an inadequate response to at least two treatment trials were randomized to treatment with rTMS or to a switch of antidepressants, both in combination with psychotherapy. Treatment duration was 8 weeks and consisted of either 25 high-frequency rTMS sessions to the left dorsolateral prefrontal cortex or a switch of antidepressant medication following the Dutch treatment algorithm. The primary outcome was change in depression severity based on the Hamilton Depression Rating Scale (HAM-D). Secondary outcomes were response and remission rates as well as change in symptom dimensions (anhedonia, anxiety, sleep, rumination, and cognitive reactivity). Finally, expectations regarding treatment were assessed. RESULTS: rTMS resulted in a significantly larger reduction in depressive symptoms than medication, which was also reflected in higher response (37.5% vs. 14.6%) and remission (27.1% vs. 4.9%) rates. A larger decrease in symptoms of anxiety and anhedonia was observed after rTMS compared with a switch in antidepressants, and no difference from the medication group was seen for symptom reductions in rumination, cognitive reactivity, and sleep disorders. Expectations regarding treatment correlated with changes in HAM-D scores. CONCLUSIONS: In a sample of patients with moderately treatment-resistant depression, rTMS was more effective in reducing depressive symptoms than a switch of antidepressant medication. In addition, the findings suggest that the choice of treatment may be guided by specific symptom dimensions.

Association between a selective 5-HT4 receptor agonist and incidence of major depressive disorder: emulated target trial.

BACKGROUND: The serotonin 4 receptor (5-HT4R) is a promising target for the treatment of depression. Highly selective 5-HT4R agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established. AIMS: To determine whether prucalopride (a 5-HT4R agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system. METHOD: Using anonymised routinely collected data from a large-scale USA electronic health records network, we conducted an emulated target trial comparing depression incidence over 1 year in individuals without prior diagnoses of major mental illness, who initiated treatment with prucalopride versus two alternative anti-constipation agents that act by different mechanisms (linaclotide and lubiprostone). Cohorts were matched for 121 covariates capturing sociodemographic factors, and historical and/or concurrent comorbidities and medications. The primary outcome was a first diagnosis of major depressive disorder (ICD-10 code F32) within 1 year of the index date. Robustness of the results to changes in model and population specification was tested. Secondary outcomes included a first diagnosis of six other neuropsychiatric disorders. RESULTS: Treatment with prucalopride was associated with significantly lower incidence of depression in the following year compared with linaclotide (hazard ratio 0.87, 95% CI 0.76-0.99; P = 0.038; n = 8572 in each matched cohort) and lubiprostone (hazard ratio 0.79, 95% CI 0.69-0.91; P < 0.001; n = 8281). Significantly lower risks of all mood disorders and psychosis were also observed. Results were similar across robustness analyses. CONCLUSIONS: These findings support preclinical data and suggest a role for 5-HT4R agonists as novel agents in the prevention of major depression. These findings should stimulate randomised controlled trials to confirm if these agents can serve as a novel class of antidepressant within a clinical setting.

Rethinking professional boundaries: the climate crisis and brain health.

Since climate change affects psychiatric, neurological and neuropsychological disorders, as well as brain development, the Irish Doctors for the Environment working group on mental health has changed its title and remit to brain health. Mental health professionals need to respond coherently and effectively to the climate crisis. This need challenges traditional professional, disciplinary and academic boundaries and demands a holistic, person-centred approach. We propose that meeting this challenge is vital if the public, policy-makers and legislators are to grasp the full extent of the significance of climate's impact on brain health.

Client perspectives: Telehealth for mental health services.

OBJECTIVE: The COVID-19 pandemic required mental health clinicians globally to transition to the delivery of care via telehealth. This study aimed to gain an understanding of clients' satisfaction with and attitudes towards telehealth mental health services. METHOD: Seventy adults who had attended a clinic for mood and anxiety disorders, and participated in at least one telehealth consultation with a psychologist or psychiatrist, completed an anonymous online survey. RESULTS: The majority of participants (81.5%) reported satisfaction with telehealth mental health care provided during the COVID-19 pandemic. However, satisfaction overall was significantly higher amongst participants who had received both telehealth and face-to-face mental health care, compared to participants who received care via telehealth only. Advantages of telehealth care reported included convenience and increased access to mental health clinicians. However, disadvantages of telehealth care included greater difficulty developing a rapport with a clinician and expressing oneself via telehealth. CONCLUSIONS: Whilst client satisfaction with telehealth mental health care for mood and anxiety disorders is generally high, clinicians should consider the limitations of telehealth from clients' perspectives. In particular, strategies to enhance therapeutic connection during telehealth sessions may be needed, and client preferences for mode of delivery should be taken into consideration when possible.

Childhood trauma and differential response to long-term psychoanalytic versus cognitive-behavioural therapy for chronic depression in adults.

BACKGROUND: Childhood trauma is a major risk factor for chronic depression. It has been suggested that adults with chronic depression who have experienced childhood trauma may require long-term treatment owing to a breakdown of basic trust and related difficulties in developing a productive therapeutic relationship. AIMS: As empirical studies have been preliminary and scarce, we studied the effects of psychoanalytic therapy (PAT) versus cognitive-behavioural therapy (CBT) for chronic depression in adults with a history of childhood trauma. In this subgroup, we expected a greater symptom reduction in PAT compared with CBT. METHOD: In a large trial of long-term psychotherapies for chronic depression (LAC-Study; Clinical Trial Register ISRCTN91956346), 210 adults received open-ended CBT or PAT in an out-patient setting and were examined yearly over 5 years on the Beck Depression Inventory - II (BDI-II). Based on a linear mixed model approach, we tested participant-reported childhood trauma based on the Childhood Trauma Questionnaire (CTQ) as a predictor and moderator of treatment outcome. CTQ subscales were examined exploratively. RESULTS: Depressive symptoms decreased over time (b = -4.55, s.e. = 0.90, 95% CI -6.32 to -2.81, T = -5.08; P < 0.001). A significant three-way interaction between childhood trauma, time and therapy group (b = -0.05, s.e. = 0.02, 95% CI -0.09 to -0.01, T = -2.42; P = 0.016) indicated that participants with childhood trauma profited especially well from PATs. CONCLUSIONS: Our results indicate differential benefits from PAT compared with CBT among adults with chronic depression and a history of childhood trauma. The results have important implications for differential indication and policy.

Effect of nature on the mental health and well-being of children and adolescents: meta-review.

BACKGROUND: Urbanisation is taking place worldwide and rates of mental illness are rising. There has been increasing interest in 'nature' and how it may benefit mental health and well-being. AIMS: To understand how the literature defines nature; what the characteristics of the nature intervention are; what mental health and well-being outcomes are being measured; and what the evidence shows, in regard to how nature affects the mental health and well-being of children and adolescents. METHOD: A meta-review was conducted, searching three databases for relevant primary and secondary studies, using key search terms including 'nature' and 'mental health' and 'mental well-being'. Inclusion criteria included published English-language studies on the child and adolescent population. Authors identified the highest quality evidence from studies meeting the inclusion criteria. Data were extracted and analysed using descriptive content analysis. RESULTS: Sixteen systematic reviews, two scoping reviews and five good quality cohort studies were included. 'Nature' was conceptualised along a continuum (the 'nature research framework') into three categories: a human-designed environment with natural elements; a human-designed natural environment; and a natural environment. The nature 'intervention' falls into three areas (the 'nature intervention framework'): access, exposure and engagement with nature, with quantity and quality of nature relevant to all areas. Mental health and well-being outcomes fit along a continuum, with 'disorder' at one end and 'well-being' at the other. Nature appears to have a beneficial effect, but we cannot be certain of this. CONCLUSIONS: Nature appears to have a beneficial effect on mental health and well-being of children and adolescents. Evidence is lacking on clinical populations, ethnically diverse populations and populations in low- and middle-income countries. Our results should be interpreted considering the limitations of the included studies and confidence in findings.

Contribution of severe mental disorders to fatally harmful effects of physical disorders: national cohort study.

BACKGROUND: It remains unknown whether severe mental disorders contribute to fatally harmful effects of physical illness. AIMS: To investigate the risk of all-cause death and loss of life-years following the onset of a wide range of physical health conditions in people with severe mental disorders compared with matched counterparts who had only these physical health conditions, and to assess whether these associations can be fully explained by this patient group having more clinically recorded physical illness. METHOD: Using Czech national in-patient register data, we identified individuals with 28 physical health conditions recorded between 1999 and 2017, separately for each condition. In these people, we identified individuals who had severe mental disorders recorded before the physical health condition and exactly matched them with up to five counterparts who had no recorded prior severe mental disorders. We estimated the risk of all-cause death and lost life-years following each of the physical health conditions in people with pre-existing severe mental disorders compared with matched counterparts without severe mental disorders. RESULTS: People with severe mental disorders had an elevated risk of all-cause death following the onset of 7 out of 9 broadly defined and 14 out of 19 specific physical health conditions. People with severe mental disorders lost additional life-years following the onset of 8 out 9 broadly defined and 13 out of 19 specific physical health conditions. The vast majority of results remained robust after considering the potentially confounding role of somatic multimorbidity and other clinical and sociodemographic factors. CONCLUSIONS: A wide range of physical illnesses are more likely to result in all-cause death in people with pre-existing severe mental disorders. This premature mortality cannot be fully explained by having more clinically recorded physical illness, suggesting that physical disorders are more likely to be fatally harmful in this patient group.

Global, regional, and national time trends in incidence for depressive disorders, from 1990 to 2019: an age-period-cohort analysis for the GBD 2019.

BACKGROUND: Even with advances in primary health care, depressive disorders remain a major global public health problem. We conducted an in-depth analysis of global, regional and national trends in depressive disorders incidence over the past 30 years. METHODS: Data on the incidence of depressive disorders were obtained by sex (female, male, and both), location (204 countries), age (5-84 years), year (1990-2019) from the Global Burden of Disease Study (GBD) 2019. Further, age-period-cohort modeling was used to estimate the net drift, local drift, age, period and cohort effects between 1990 and 2019. RESULTS: In 2019, although the incidence of depressive disorders has increased by 59.3% to 290 million (95% UI: 256, 328), the age-standardized incidence rate has decreased by 2.35% to 3588.25 per 100,000 people (3152.71, 4060.42) compared to 1990. There was an emerging transition of incidences from the young and middle-aged population to the old population. From 1990 to 2019, the net drift of incidence rate ranged from -0.54% (-0.61%, -0.47%) in low-middle Socio-demographic Index (SDI) regions to 0.52% (0.25%, 0.79%) in high SDI regions. Globally, the incidence rate of depressive disorders increases with age, period effects showing a decreasing risk and cohort effects beginning to decline after the 1960s. CONCLUSIONS: Our current findings reflect substantial health disparities and potential priority-setting of depressive disorders incidence in the three dimensions of age, period and cohort across SDI regions, countries. The scope of healthcare to improve the progression of depressive disorders events can be expanded to include males, females of all ages.

Global, regional, and national temporal trends in prevalence for depressive disorders in older adults, 1990-2019: An age-period-cohort analysis based on the global burden of disease study 2019.

As a severe public health issue, depressive disorders (DD) has caused an increasingly burden of disease, especially in the older adults. To provide an overview and in-depth analysis of temporal trends in prevalence of DD in older adults at global, regional, and national levels over the last 30 years. Here, an age-period-cohort model was adopted to analyze age, period, and cohort effects. We showed that the global prevalence of DD in older adults was increasing. The net drift of the global prevalence of DD was showing an increasing trend in 78 countries, while local drift showing a declining trend in all age groups in high sociodemographic index (SDI) region. Additionally, period and cohort effects exhibited different patterns across regions. Over time, the declining trend was most significant in high SDI regions, while this trend was most significant in middle SDI region. Interestingly, those aged 60-64 years to 70-74 years was increasing globally, while age group aged 75-79 years to 95-99 years was on declining. In high, high-middle, and low SDI regions, individuals born early face higher risks than those born late, while the opposite results were observed in low-middle SDI region. Overall, our findings offer a insight global perspective for studying the temporal trends of DD prevalence, supplementing our evidence and understanding of DD epidemiology, and identifying gaps in DD prevention, management, and intervention plans in different aspects.

Predictors of Depressive Symptoms in Autistic Youth-A Longitudinal Study From the Province of Ontario Neurodevelopmental Disorders (POND) Network: Prédicteurs des symptômes dépressifs chez les jeunes autistes-une étude longitudinale du Réseau des troubles neurodéveloppementaux de la province de l'Ontario (réseau POND).

OBJECTIVE: The objective of this study was to identify longitudinal predictors of depressive symptoms in autistic children and youth. METHODS: Participants were youth with a diagnosis of autism who were part of the Province of Ontario Neurodevelopmental Disorders Network longitudinal substudy. Depressive symptoms were assessed using the child behaviour checklist (CBCL) affective problems subscale. Univariate and multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between clinical and demographic characteristics at baseline (T1) and clinically elevated depressive symptoms (CEDS) approximately 4 years later (T2). RESULTS: The mean age of participants (n = 75) at T1 was 9.8 years (SD = 2.7) and at T2 was 14.1 years (SD = 2.8). A total of 37% and 35% of participants had CEDS at T1 and T2, respectively. Additionally, 24% of participants had CEDS at both T1 and T2. T1 characteristics associated with T2 CEDS were: loneliness (OR = 3.0, 95% CI, 1.1 to 8.8), self-harm (OR = 4.0, 95% CI, 1.1 to 16.9), suicidal ideation (OR = 3.9, 95% CI, 1.0 to 16.5), more social and adaptive skills (OR = 0.3, 95% CI, 0.1 to 0.9), elevated restricted and repetitive behaviours (OR = 3.8, 95% CI, 1.3 to 11.6), psychotropic medication use (OR = 3.0, 95% CI, 1.1 to 8.4), attention-deficient/hyperactivity disorder (OR = 2.8, 95% CI, 1.1 to 7.8), and T1 CEDS (OR = 8.8, 95% CI, 3.1 to 27.0) (uncorrected for multiple comparisons). Associations persisted after adjusting for age and intelligence quotient (IQ) differences. Age, sex, IQ, teasing/bullying on the CBCL, family psychiatric history and family income were not associated with T2 CEDS. CONCLUSION: Our results highlight both high prevalence and high potential for the persistence of depressive symptoms in autism and emphasize the importance of early support to address loneliness and social participation.

Study assessing risk factors for depression in autistic youthPlain Language SummaryObjectiveThe goal of this study was to find risk factors for depression in autistic youth.MethodsThe study included autistic youth who were part of the Province of Ontario Neurodevelopmental Disorders Network. Symptoms of depression were identified using mental health surveys and screening tools completed by parents. We studied 75 youth over two time points, to understand what factors might predict greater depression risk.ResultsThe average age of our study population at the first visit was 10 years old, and 14 years old at the second visit. Our study found that 37% of participants had elevated symptoms of depression at the first visit, and 35% at the second visit. Factors associated with future depressive symptoms included: loneliness, self-harm, suicidal ideation, high levels of restrictive/repetitive behaviours, depressive symptoms at the first visit, and ADHD. Factors that protected against depressive symptoms included high levels of social skills.ConclusionOur results show high levels of depressive symptoms among autistic youth, and the potential for this to persist over time in this population. Our findings emphasize the importance of early supports to address loneliness and social participation.

Global burden of major depressive disorders attributable to intimate partner violence against women: Magnitude, temporal trends, and regional inequalities.

AIMS: This study aimed to analyze the temporal trends, spatial heterogeneities, and potential improvements in the burden of major depressive disorders (MDD) attributable to intimate partner violence (IPV) against women across 21 global burden of disease (GBD) regions, and 204 countries and territories from 1990 to 2019. METHODS: We evaluated the burden of MDD attributable to IPV against women, as measured in disability-adjusted life years (DALYs) per 100,000 people across 21 GBD regions and 204 GBD countries and territories, using data from the 2019 GBD Study. The average annual percentage change (AAPC) of the DALY age-standardized rates (ASRs) was used to reflect trends over time. LOESS and quantile regression were used to model the relationship between the five GBD sociodemographic index (SDI) categories and DALY ASRs. Frontier analysis determined the minimum achievable DALY ASR associated with developmental status, as measured by the SDI. RESULTS: The overall AAPC in age-standardized DALY rates for MDD attributable to IPV declined globally between 1990 and 2019. Despite the overall global decline (AAPC -0.08 [95 % UI -0.2, 0.03]), certain GBD regions, particularly high-income North America and Central Latin America, have experienced increases in DALY ASRs. The relationship between SDI and MDD burden showed a U-shaped variability, with low-SDI regions consistently exhibiting higher and stable DALY rates. Frontier analysis revealed that several countries, regardless of their SDI, have substantial gaps between observed and potentially achievable DALY rates, indicating areas for targeted intervention to reduce the burden of MDD due to IPV. CONCLUSIONS: Significant spatial and temporal heterogeneity in MDD due to IPV was observed globally from 1990 to 2019, highlighting the substantial potential for improvement in various countries. Protective measures should be customized to suit the unique cultural contexts, developmental statuses, and regional disparities of each country.

[Fluvoxamine in the treatment of anxiety-depressive spectrum disorders]. / Fluvoksamin pri lechenii rasstroistv trevozhno-depressivnogo spektra.

The RSCI and PubMed search databases have requested publications over the past 40 years on the search queries «fluvoxamine¼, «anxiety-depressive disorders¼, «anxiety¼, «depression¼, «comorbidity¼, devoted to the effectiveness of fluvoxamine in various variants of disorders of the anxiety-depressive spectrum, anxiety depressions. The data of the above studies indicate that fluvoxamine (Zovart San) in doses of 50-300 mg / day is a highly effective remedy for the treatment of not only anxiety depressions and genesis (psychogenic, organic, mixed, autochthonous-endogenous) and severity (up to psychotic), but also a wider range of anxiety-depressive disorders, including adaptation disorders, obsessive-compulsive disorder, somatized, dysmorphic, insomniac symptom complexes and eating disorders. A wide range of clinical effects of fluvoxamine is due to its main and additional mechanisms of action: blockade of serotonin reuptake, σ1-agonist activity and the effect on the metabolism of melatonin and neurosteroids catabolism.

Optimizing and Predicting Antidepressant Efficacy in Patients with Major Depressive Disorder Using Multi-Omics Analysis and the Opade AI Prediction Tools.

According to the World Health Organization (WHO), major depressive disorder (MDD) is the fourth leading cause of disability worldwide and the second most common disease after cardiovascular events. Approximately 280 million people live with MDD, with incidence varying by age and gender (female to male ratio of approximately 2:1). Although a variety of antidepressants are available for the different forms of MDD, there is still a high degree of individual variability in response and tolerability. Given the complexity and clinical heterogeneity of these disorders, a shift from "canonical treatment" to personalized medicine with improved patient stratification is needed. OPADE is a non-profit study that researches biomarkers in MDD to tailor personalized drug treatments, integrating genetics, epigenetics, microbiome, immune response, and clinical data for analysis. A total of 350 patients between 14 and 50 years will be recruited in 6 Countries (Italy, Colombia, Spain, The Netherlands, Turkey) for 24 months. Real-time electroencephalogram (EEG) and patient cognitive assessment will be correlated with biological sample analysis. A patient empowerment tool will be deployed to ensure patient commitment and to translate patient stories into data. The resulting data will be used to train the artificial intelligence/machine learning (AI/ML) predictive tool.

The Glutamatergic Effects of Clinical Repetitive Transcranial Magnetic Stimulation in Depressed Populations: A Preliminary Meta-Analysis of Proton Magnetic Resonance Spectroscopy Studies.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) alleviates symptoms of major depressive disorder, but its neurobiological mechanisms remain to be fully understood. Growing evidence from proton magnetic resonance spectroscopy (1HMRS) studies suggests that rTMS alters excitatory and inhibitory neurometabolites. This preliminary meta-analysis aims to quantify current trends in the literature and identify future directions for the field. METHODS: Ten eligible studies that quantified Glutamate (Glu), Glu+Glutamine (Glx), or GABA before and after an rTMS intervention in depressed samples were sourced from PubMed, MEDLINE, PsychInfo, Google Scholar, and primary literature following PRISMA guidelines. Data were pooled using a random-effects model, Cohen's d effect sizes were calculated, and moderators, such as neurometabolite and 1HMRS sequence, were assessed. It was hypothesized that rTMS would increase cortical neurometabolites. RESULTS: Within-subjects data from 224 cases encompassing 31 neurometabolite effects (k) were analyzed. Active rTMS in clinical responders (n = 128; k = 22) nominally increased glutamatergic neurometabolites (d = 0.15 [95% CI: -0.01, 0.30], p = 0.06). No change was found in clinical nonresponders (p = 0.8) or sham rTMS participants (p = 0.4). A significant increase was identified in Glx (p = 0.01), but not Glu (p = 0.6). Importantly, effect size across conditions were associated with the number of rTMS pulses patients received (p = 0.05), suggesting dose dependence. CONCLUSIONS: Clinical rTMS is associated with a nominal, dose-dependent increase in glutamatergic neurometabolites, suggesting rTMS may induce Glu-dependent neuroplasticity and upregulate neurometabolism. More, larger scale studies adhering to established acquisition and reporting standards are needed to further elucidate the neurometabolic mechanisms of rTMS.

A Randomized Controlled Trial Comparing the Quality of Life and Medication Adherence in Patients on Antidepressant Monotherapy.

Background and objectives The quality of life declines with the growing severity of major depressive disorder (MDD). In depressed people, medication adherence and the quality of life are mutually corrosive. These concerns spurred the investigation of relationships between treatment outcomes and adherence levels. Limited studies are looking at how vortioxetine, escitalopram, and vilazodone affect these parameters. We aimed to detect how the Short Form-36 (SF-36) had changed 16 weeks after the baseline. The connection between treatment results (as expressed by the Hamilton Depression Rating Scale or HDRS) and medication adherence (as reflected by the Morisky Medication Adherence Scale-8 or MMAS-8) was also explored. Methods An open-label, randomized, three-arm trial with 96 MDD patients was conducted. For 16 weeks, the participants were put into three groups per a 1:1:1 ratio and administered tablets of vilazodone (20-40 mg/day), escitalopram (10-20 mg/day), or vortioxetine (5-20 mg/day). There were two test drugs: vilazodone and vortioxetine; the control was escitalopram. Four weeks apart, follow-up appointments were set after the baseline visit. The HDRS, mental and physical components of SF-36, and MMAS-8 scores were evaluated in the per-protocol (PP) population. Reduced HDRS scores were indicative of improved depression symptoms. Higher MMAS-8 and SF-36 scores indicated high drug adherence and enhanced quality of life. Our analysis used the Kruskal-Wallis test, the Bonferroni correction, and the Sankey diagram. In the Clinical Trial Registry-India (CTRI), we recorded this study prospectively (2022/07/043808). Results One hundred nine (81.34%) of the 134 individuals we examined were eligible. The PP population consisted of 96 (88.07%) of them who wrapped up the 16-week study. The mean age of the group was 46.3 ± 6.2 years. For each of the three groups, the SF-36 physical component scores revealed a median difference of 24.5 (23.8-26.0), 24.0 (22.8-25.3), and 27.0 (25.0-29.0) (p = 0.001). Accordingly, the mental components of their SF-36 scores showed a median difference of 32.0 (31.0-33.3), 31.0 (29.8-34.3), and 36.0 (33.0-38.0) (p = 0.001). A median difference of -15.0 (-16.0 to -14.0), -16.0 (-17.0 to -15.0), and -16.0 (-17.0 to -15.8) was observed in the HDRS scores after 16 weeks, with respect to the baseline (p < 0.001). The median MMAS-8 scores at 16 weeks were 6.0 (6.0-7.0), 6.8 (6.0-7.0), and 7.5 (6.5-8.0) (p = 0.031). The Sankey diagram illustrated the connection between better treatment results, increased medication compliance, and decreased symptoms of depression. Conclusion In comparison to vilazodone and escitalopram, vortioxetine demonstrated a statistically significant decrease in HDRS scores and an improvement in the physical and mental component scores of the SF-36. Clinical improvements were evident in the individuals' drug adherence levels. Larger-scale studies are advised to investigate the effects of these medications on the quality of life, medication adherence, and treatment outcomes.