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The suicide rate in youth and young adults continues to climb - we do not understand why this increase is occurring, nor do we have adequate tools to predict or prevent it. Increased efforts to treat underlying depression and other disorders that are highly associated with suicide have had limited impact, despite considerable financial investments in developing and disseminating available methods. Thus, there is a tremendous need to identify potential markers of suicide behavior for youth during this high-risk period.Funded by the American Foundation for Suicide Prevention (AFSP), this study aims to map immune dysfunction to suicidal behavior and establish a reliable immune signature of suicide risk that can 1) guide future research into fundamental pathophysiology and 2) identify targets for drug development. The study design is an observational study where blood samples and a comprehensive array of clinical measures are collected from three groups of adolescents (n = 75 each) (1) with suicidal behavior [recent (within 3 months) suicide attempt or suicidal ideation warranting urgent evaluation,] (2) at risk for mood disorders, and (3) who are healthy (no psychiatric history). Participants will complete self-report and clinical assessments, along with a blood draw, at baseline, 3 months, 6 months and 12 months, and online self-report assessments once a month.The recruitment for this study is ongoing.Observational, variability in treatment regimens.This study will help elucidate immune mechanisms that may play a causal role in suicide and serve as targets for future therapeutic development.

To address the clinical heterogeneity of Major Depressive Disorder (MDD), this investigation determined whether resting state functional magnetic resonance imaging (fMRI) could be deployed to identify circuit based homogeneous subgroups, and whether subgroups identified show differential treatment outcomes.Pretreatment resting state fMRIs obtained from 278 outpatients with nonpsychotic MDD from Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression Study were used to create data-driven subgroups using CLICK clustering. These subgroups were then compared using baseline clinical data, as well as baseline-to-week 8 changes in depression severity measured using the 17-item Hamilton Rating Scale for Depression (HAMDThree subgroups were identified. Cluster-1 was characterized by overallhyperconnectivity coupled with profound hypoconnectivity between the supramarginal gyrus (executive control network; ECN) and the superior frontal cortex (dorsal attention network; DAN). Cluster-2 was characterized by overall hypoconnectivity coupled with hyperconnectivity between supramarginal gyrus (ECN) and superior frontal cortex (DAN). Cluster-3 showed hypoconnectivity, especially profound between the angular cortex (default mode network; DMN) and middle frontal cortex (ECN). While baseline clinical measures did not differentiate the three clusters, Cluster-3 had the remission rate (51.6%) compared to Cluster-1 and Cluster-2 (32.7% and 31.9%) when treated with sertraline.Due to the exploratory nature of these analyses, there were no adjustments for multiple comparisons.Baseline functional connectivity can be used to subgroup patients with MDD that differ in acute phase treatment outcomes. Measures of connectivity may address the heterogeneity of MDD.

Although insomnia is a common core symptom of major depressive disorder (MDD), the burden of moderate-to-severe insomnia symptoms in patients with MDD is not well-understood. This study quantified the clinical, patient-centric, and economic burden of adults with MDD with moderate-to-severe insomnia symptoms (MDDIS) compared to adults with MDD with no-to-mild insomnia symptoms (other-MDD) and adults without MDD.Data from 2019 US National Health and Wellness Survey identified adults self-reporting physician-diagnosed depression, stratified by insomnia status (MDDIS: Insomnia Severity Index [ISI] score ≥15; other-MDD: ISI score 15), and adults not reporting depression (non-MDD). Other-MDD and non-MDD were matched 2:1 to MDDIS on age/sex/race. Matched bivariate analyses examined differences in health-related outcomes by depression-insomnia status.Of 74,994 survey respondents, 2045 (2.7%) were classified as MDDIS, 8220 (11.0%) as other-MDD, and 59,859 (79.8%) as non-MDD. MDDIS respondents (vs other-MDD and non-MDD) reported greater depression severity, anxiety severity, daytime sleepiness, activity impairment, direct costs, and costs due to work productivity impairments, and lower mental and physical functioning (all P 0.05).Depression diagnosis was not based on clinical/diagnostic interview; causal relationships cannot be determined due to the cross-sectional design.Among US adults with MDD, presence of moderate-to-severe insomnia symptoms is associated with additional burden and notable impairments across several health outcomes versus those with MDD but no-to-minimal insomnia symptoms and general population without MDD. This study highlights the burden of MDDIS and the need for better identification and management of moderate-to-severe insomnia symptoms in adults with MDD.

Purpose This report from VitalSign6 project describes treatment selection, follow-up rates and remission outcomes by initial depression severity using the PCP-FIRST model. Methods This retrospective analysis included 32,106 patients aged ≥12 years screened with the Patient Health Questionnaire 2-item (PHQ-2) from November 2016 to July 2019 across 37 primary care clinics. PHQ-2 positive-screen patients (PHQ-2 ≥ 3) received 9-item PHQ (PHQ-9) and 7-item Generalized Anxiety Disorder scales, clinician assessments, and evaluation for pharmacotherapy management with measurement-based care (MBC). Results Of PHQ-2 screened patients, 18.7% (5994/32,106) were positive and received a PHQ-9. Of 5994 patients with PHQ-9, 2571 received a clinical diagnosis of depression of whom, 333 had none-mild depression (PHQ-9 Conclusions Despite this being a real-world, usual care sample, remission outcomes exceed real world remission rate expectations of 6% in primary care.

Recent studies have suggested that mitochondrial dysfunction and dysregulated neuroinflammatory pathways are involved in the pathophysiology of major depressive disorder (MDD). Here, we aimed to assess the differences in markers of mitochondrial dynamics, mitophagy, general autophagy, and apoptosis in peripheral blood mononuclear cells (PBMCs) of MDD patients (n = 77) and healthy controls (HCs, n = 24). Moreover, we studied inflammation engagement as a moderator of mitochondria dysfunctions on the severity of depressive symptoms. We found increased levels of Mfn-2 (p

To evaluate the impact of baseline irritability on clinical outcomes in adults with treatment-resistant depression (TRD) treated with fixed or flexible doses of esketamine nasal spray plus a newly initiated oral antidepressant (ESK+AD) and to explore whether treatment with ESK affects irritability symptoms over time.This was a post hoc analysis of pooled data from two 4-week, double-blind, phase 3 studies: TRANSFORM-1 (NCT02417064) and TRANSFORM-2 (NCT02418585). Adults with TRD (n = 560) were randomly assigned to ESK+AD or placebo nasal spray plus oral antidepressant (AD+PBO). Irritability was assessed with Item 6 of the 7-item Generalized Anxiety Disorder scale at screening and baseline. Changes in depression severity (Montgomery-Åsberg Depression Rating Scale [MADRS] total score) were evaluated by analysis of covariance (ANCOVA) models. Rates of MADRS response (≥50 % decrease from baseline total score) and remission (total score ≤ 12) were examined using multiple logistic regression models.Of 560 participants with TRD, 52.9 %, 23.2 %, and 23.9 % had high, low, and varying levels of irritability, respectively. No significant interaction between baseline irritability and treatment group was observed for change in MADRS total score, treatment response, or remission at day 28; numerically greater improvement was observed on all outcomes with ESK+AD versus AD+PBO at day 28 regardless of baseline irritability level. Percentages of patients reporting adverse events were similar across the three baseline irritability groups.TRANSFORM-1 and TRANSFORM-2 were not designed to prospectively evaluate predetermined irritability outcomes.These post hoc results support efficacy of ESK+AD in patients with TRD, regardless of baseline irritability.ClinicalTrials.gov identifiers: NCT02417064 (TRANSFORM-1), NCT02418585 (TRANSFORM-2).

Promising initial data indicate that the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine may be beneficial in post-traumatic stress disorder (PTSD). Here, we explore the neural correlates of ketamine-related changes in PTSD symptoms, using a rich battery of functional imaging data (two emotion-processing tasks and one task-free scan), collected from a subset of participants of a randomized clinical trial of repeated-dose intravenous ketamine vs midazolam (total N=21). In a pre-registered analysis, we tested whether changes in an a priori set of imaging measures from a target neural circuit were predictive of improvement in PTSD symptoms, using leave-one-out cross-validated elastic-net regression models (regions of interest in the target circuit consisted of the dorsal and rostral anterior cingulate cortex, ventromedial prefrontal cortex, anterior hippocampus, anterior insula, and amygdala). Improvements in PTSD severity were associated with increased functional connectivity between the ventromedial prefrontal cortex (vmPFC) and amygdala during emotional face-viewing (change score retained in model with minimum predictive error in left-out subjects, standardized regression coefficient [β]=2.90). This effect was stronger in participants who received ketamine compared to midazolam (interaction β=0.86), and persisted following inclusion of concomitant change in depressive symptoms in the analysis model (β=0.69). Improvement following ketamine was also predicted by decreased dorsal anterior cingulate activity during emotional conflict regulation, and increased task-free connectivity between the vmPFC and anterior insula (βs=-2.82, 0.60). Exploratory follow-up analysis via dynamic causal modelling revealed that whilst improvement in PTSD symptoms following either drug was associated with decreased excitatory modulation of amygdala→vmPFC connectivity during emotional face-viewing, increased top-down inhibition of the amygdala by the vmPFC was only observed in participants who improved under ketamine. Individuals with low prefrontal inhibition of amygdala responses to faces at baseline also showed greater improvements following ketamine treatment. These preliminary findings suggest that, specifically under ketamine, improvements in PTSD symptoms are accompanied by normalization of hypofrontal control over amygdala responses to social signals of threat.

The measurement of thermal conductivity of granitic rocks is a time-consuming process and requires highly sophisticated instruments for experimental analysis. The difficulties in proposing reliable and precise empirical correlations and theoretical models forced the researchers to use alternative and more accurate models based on artificial intelligence (AI) techniques. The present study has been carried out to predict two parameters, thermal conductivity, and damage threshold for Jalore granite using AI techniques. In this study, artificial neural networks (ANNs), linear regression, support vector regressors (SVRs),, and decision tree regressors (DTRs) have been applied to obtain reliable and more accurate models. The extensive analysis revealed that the optimum performance is obtained by the ANN model with 8 nodes in the input layer with 2 hidden layers. Hidden layers having 15 and 7 nodes in the first and second layers, respectively. Softmax function has been applied as activation for each layer of the developed model. The mean absolute error (MAE) and mean squared error (MSE) values for the model while predicting the thermal coefficient were 0.0033671 and 184E−05. These values were 0.0016141 and 3.89E−06 for the damage threshold. DTRs with the number of estimators, n = 100, 1000, and 10,000 perform relatively well for predicting the values for both parameters. Linear regression and SVRs models (linear and robust kernel) show some deviations from the observed values at points where the trend shows a sudden change or kink. In the case of DTRs, the model with the number of estimators, n = 1000, and 100 performs most efficiently for predicting thermal conductivity (MSE = 6.81E−05) and the damage threshold (MSE = 2.84E−05), respectively.

Disasters and crisis are becoming more complex with deadly cascading effects. The current coronavirus pandemic is viewed as the newest form of health and socio-economic crisis that has disrupted the flow of normal life for millions. Viewing the pandemic as a unique or unpredictable occurrence shifts responsibility and accountability from a host of institutional actors to those who were unable to protect themselves from the direct and indirect effects of the pandemic and incurred heavy losses. Situating the pandemic within the well-established policy debates around disasters enables us to understand how the novel coronavirus rapidly transformed into a humanitarian crisis in India. Successful disaster risk reduction involves the creation of a “culture of resilience” but resilience thinking has been criticized as lacking in “moral compass”, showing a poor understanding of power relations and as governance that emphasizes individual responsibility. Chronically poor people can be “resilient” at the expense of their long-term wellbeing. Drawing on the moral, political and philosophical debates about the shift toward “resilience” in global disaster policy, this article examines the rhetoric of “self-reliance” to address COVID-19 dislocation. We find that disaster policies that rely mainly on resilience and compliance increase state power while absolving them of responsibility. © 2021 Taylor & Francis.

Sociotropy and autonomy are cognitive-personality styles that have been hypothesized to confer vulnerability to different presentations of major depressive disorder (MDD), which may respond differentially to treatment. Specifically, the profile of low sociotropy and high autonomy is hypothesized to indicate a positive response to antidepressant medication. The current study examines sociotropy and autonomy in relation to sertraline treatment response in individuals with MDD. As part of an ancillary study to the larger Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) project, individuals with MDD participated in an 8-week trial of sertraline and completed a self-report questionnaire of sociotropy and autonomy. Discriminant function analyses were used to examine whether sociotropy and autonomy scores could distinguish antidepressant treatment responders (determined by a 50% or greater reduction in depressive symptoms) from non-responders. The sociotropy scale successfully discriminated sertraline treatment responders from non-responders. Further, lower sociotropy was associated with greater improvements in depressive symptomology following sertraline treatment. The current findings suggest individuals with MDD characterized by low sociotropy are more likely to benefit from sertraline. Given the promising results of the Sociotropy-Autonomy Scale in discriminating treatment responders from non-responders, the low resources necessary for administration, and the ease of translation into routine clinical care, the scale warrants further research attention.

Ketamine is an N-methyl-D-aspartate receptor antagonist with rapid antidepressant effects. Studies suggest that inhibition of nitric oxide synthesis plays a role in the mechanism of action of ketamine. This randomized, placebo-controlled study investigated whether co-administration of sodium nitroprusside, a nitric oxide donor, compared to placebo, would attenuate the antidepressant and dissociative effects of ketamine. Sixteen ketamine responders were randomized to a double-blind infusion of ketamine co-administered with placebo or sodium nitroprusside. Our findings show no difference between the two conditions suggesting that the nitric oxide pathway may not play a primary role in ketamine’s antidepressant or dissociative effects. The study is registered at clinicaltrials.gov (NCT03102736).

Background Adults with major depressive disorder (MDD) often experience reduced quality of life (QOL). Efficacious acute-phase treatments, including cognitive therapy (CT) or medication, decrease depressive symptoms and, to a lesser degree, increase QOL. We tested longer-term changes in QOL after response to acute-phase CT, including the potential effects of continuation treatment for depression and time-lagged relations between QOL and depressive symptoms. Methods Responders to acute-phase CT (N = 290) completed QOL and depressive symptom assessments repeatedly for 32 post-acute months. Higher-risk responders were randomized to 8 months of continuation treatment (CT, fluoxetine, or pill placebo) and then entered a 24-month follow-up. Lower-risk responders were only assessed for 32 months. Results On average, large gains in QOL made during acute-phase CT response were maintained for 32 months. Continuation CT or fluoxetine did not improve QOL relative to pill placebo. Controlling for residual depressive symptoms, higher QOL after acute-phase CT response was a protective factor against MDD relapse and recurrence. Higher QOL predicted subsequent reductions in depressive symptom severity, but depressive symptom severity did not predict subsequent changes in QOL. Limitations Generalization of results to other patient populations, treatments, and measures is uncertain. The clinical trial was not designed to test relations between QOL and depression. Replication is needed before clinical application of these results. Conclusions Gains in QOL made during response to acute-phase CT are relatively stable and may help protect against relapse/recurrence. Continuation CT or fluoxetine may not further improve QOL among acute-phase CT responders.

Major depressive disorder (MDD) is widely prevalent and one of the leading causes of disability. Treatment outcomes remain suboptimal with 1 in 3 patients with MDD responding inadequately to commonly used antidepressants. Pimavanserin, an atypical antipsychotic that modulates serotonergic neurotransmission by selectively binding to serotonin receptor (2A and 2C) subtypes and without dopaminergic activity, may have the potential as an adjunctive treatment for MDD. In a phase 2 trial (n=203), addition of pimavanserin, as compared to placebo, to stable treatment with antidepressants was associated with greater reduction in 17-item Hamilton Depression Rating Scale score [HAMD, least square means (95% confidence interval) of −1.7 (−0.03, −3.37), p=0.039]. Furthermore, treatment with pimavanserin was associated with significantly greater improvement in specific symptoms associated with depression such as impaired sexual function, anxiety, sleepiness, and irritability. However, the availability of pimavanserin for clinical care of patients with MDD remains uncertain. Top-line results of phase 3 studies (n=298) that were announced by the sponsor found similar reductions in HAMD (mean baseline-to-week-5 reduction of 9.0 and 8.1, p=0.296) and rates of adverse events (58.1% and 54.7%) with addition of pimavanserin and placebo respectively to stable treatment with antidepressants. Given the potential benefit for specific symptoms such as impaired sexual function, anxiety and sleep/wakefulness disturbances, future studies that enrich for these symptoms may be needed to clarify the utility of adjunctive pimavanserin in treatment of patients with MDD.

Background: Chronic Obstructive Pulmonary Disease (COPD) is chronic inflammatory condition that is known to be a prothrombotic state. Objective: To study the prothrombotic markers and coagulation profile in patients of Stable COPD and during its exacerbation and to compare these parameters in stable phase of disease and during exacerbation. Materials and Method: A cross sectional study in which 30 patients of COPD with exacerbation and 30 patients with stable COPD were recruited. Patients having acquired thrombotic risk factors like diabetes, hypertension, coronary artery disease, chronic kidney disease, chronic liver disease, malignancy & sepsis or any immunocompromised condition along with those who were on anticoagulant therapy, statins or antihypertensive medications were excluded from the study. Levels of prothrombotic markers (von Willebrand Factor antigen, D-dimer, fibrogen) and Caogulation profile (Prothrombin time and activated Partial Thromboplastin Time) were estimated in both the groups and repeated after stabilization of exacerbation phase also. There parameters were then statistically analyzed. Observation and Results: A generalized prothrombotic state was observed in exacerbation phase of COPD as compared to stable phase of COPD. Furthermore, all the parameters including fibrinogen, vWF, PT and aPTT showed persistent declining trend from exacerbation towards stabilization. Conclusion: COPD with acute exacerbation is a state of augmented prothrombotic state. On stabilization of acute exacerbation with treatment, coagulation profile came to a level lower than that of patients in stable phase of COPD. In exacerbation phase of COPD vWF values were significantly elevated than in stable phase. How to cite this article: Daga MK, Kumar N, Singh S, Mawari G, Mahapatra SJ, Jha Mk et al. Study of Prothrombotic Markers in COPD. J Adv Res Med 2020; 7(4): 1-6. DOI: https://doi.org/10.24321/2349.7181.202014

Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of mortality and loss of Disability-Adjusted Life-Years (DALYs) worldwide. It often is accompanied by the presence of various systemic comorbidities including osteoporosis which may have an impact on the course of the disease. Osteopenia and osteoporosis are the consequences of loss of Bone Mineral Density (BMD) and have been widely known major comorbidities in COPD patients. Female sex, age, and smoking are common pathogenic factors for both COPD and osteoporosis, other factors such as reduced daily physical activity, malnutrition, low body mass index, hypogonadism, vitamin D deficiency, chronic renal insufficiency, chronic hypoxemia, and drugs like corticosteroids, have been invoked to explain such a frequent association between them. Osteoporosis in COPD is however often undertreated. It has been shown in recent studies that both decreased Bone Mineral Density (BMD) and impaired bone quality contribute to bone fragility, causing fractures in COPD patients. Pulmonary function and activities of the daily life of COPD patients may be further deteriorated by osteoporosis-associated fractures. Calcium and vitamin D, hormone replacement when indicated, calcitonin, and bisphosphonate administration are few effective strategies to tackle bone loss and osteoporosis. Awareness about this high prevalence of osteoporosis in COPD patients is critically important and physicians should look for such fracture risks. Routine screening and early diagnosis of osteoporosis will enable physicians to provide the appropriate treatment to prevent fracture, which leads to improved quality of life as well as better long-term prognosis. How to cite this article:Daga MK, Kumar N, Raghu RV, Mawari G, Chand S, Aarthi J. Osteoporosis in Chronic Obstructive Pulmonary Disease: More than just a Comorbidity. J Adv Res Med 2020; 7(3): 7-12. DOI: https://doi.org/10.24321/2349.7181.202011

Social Policy is concerned with minimising poverty and inequality through redistribution of goods and services. In the twentieth century, after the Second World War, European parliamentary democracies enlarged its ambit by making social policy an important instrument to create equality setting the benchmark for other countries. For the new independent countries in the global South, such as India, social policy followed different trajectories. In the aftermath of independence, India relied on preventive instruments to address the effects of famine, de-industrialisation and high levels of deprivation. Despite achieving high economic growth and rapid poverty reduction in the following decades, its dependence on targeted poverty reduction programme has remained. Recently, there has been some attempt to replace these strategies by rights-based programmes supported by legal framework advocated by civil society groups. Through a case study of The Scheduled Tribes and Other Traditional Forest Dwellers (Recognition of Forest Rights) Act, 2006 (referred to as FRA 2006), this article analyses the successes and failures in realising the goal of linking welfare provisions with the ideas of social citizenship and democratic rights. The article finds widening gulf in the interests of state actors and local community arising from the compromised interpretation of the social justice vision enshrined in FRA.

With complex sociopolitical contours around the idea of ethnicity, identity and citizenship, communities are experiencing unprecedented violence and vulnerabilities. The life and circumstances of one of such contentious community, Rohingya, is a telling example of an assault on their identity, culture, and history. The state sponsored violence and persecution had forced them to flee Myanmar. Denied recognition, as refugee or asylum seeker anywhere in the world, more than a million people from the community has become ‘stateless’ and living in a precarious condition in the camps in Bangladesh. This article explains the process whereby a community’s identity and citizenship were undermined, forcing them to become a stateless community. The article explores: what role identity, ethnicity, and politics play vis-a-vis minority communities at the ‘margin’? What complex challenges does it pose for community work and how community work attempts to take on that challenge? The article explains how sociocultural specificity poses a challenge for community workers to rely on their received wisdom. Therefore, approaches, strategies, and skills require substantive modification and alignment. Drawing upon personal interviews with key informants (coordinators of humanitarian response, community leaders, camp residents, and host community) and analysis of the documentary sources, the article brings forth the nature and character of community work undertaken by people coming from the varied disciplinary background.

As countries shore up existing safeguards to address the social and economic impacts of the COVID-19 pandemic, India faces a humanitarian disaster of unprecedented proportions. Ninety per cent of the Indian workforce is employed in the unorganised sector; uncounted millions work in urban areas at great distances from rural homes. When the Government of India (GOI) announced the sudden ‘lockdown’ in March to contain the spread of the pandemic, migrant informal workers were mired in a survival crisis, through income loss, hunger, destitution and persecution from authorities policing containment and fearful communities maintaining ‘social distance’. In this context, the article analyses how poverty, informality and inequality are accentuated by the COVID-19 pandemic experiences of ‘locked down’ migrant workers. The article examines the nature and scope of existing social policy, designed under changing political regimes and a fluctuating economic climate, to protect this vulnerable group and mitigate dislocation, discrimination and destitution at this moment and in future.

BACKGROUND Sexual dysfunction is common among patients with major depressive disorder (MDD). In the CLARITY study, the safety and efficacy of adjunctive pimavanserin, an inverse agonist at 5-HT2A receptors, were demonstrated when added to existing treatment for MDD. This analysis provides a detailed assessment of the effects of pimavanserin on sexual function from the CLARITY study. METHODS Patients with a diagnosis of MDD in a depressive episode, inadequate response to ongoing antidepressant therapy, and a Montgomery-Asberg Depression Rating Scale total score >20 were randomized to pimavanserin 34 mg/day or placebo added to ongoing treatment with an immediate revision of all selective serotonin or serotonin-norepinephrine for 5 weeks (Stage 1), and nonresponders (

Antidepressants are widely prescribed, but their efficacy relative to placebo is modest, in part because the clinical diagnosis of major depression encompasses biologically heterogeneous conditions. Here, we sought to identify a neurobiological signature of response to antidepressant treatment as compared to placebo. We designed a latent-space machine-learning algorithm tailored for resting-state electroencephalography (EEG) and applied it to data from the largest imaging-coupled, placebo-controlled antidepressant study (n = 309). Symptom improvement was robustly predicted in a manner both specific for the antidepressant sertraline (versus placebo) and generalizable across different study sites and EEG equipment. This sertraline-predictive EEG signature generalized to two depression samples, wherein it reflected general antidepressant medication responsivity and related differentially to a repetitive transcranial magnetic stimulation treatment outcome. Furthermore, we found that the sertraline resting-state EEG signature indexed prefrontal neural responsivity, as measured by concurrent transcranial magnetic stimulation and EEG. Our findings advance the neurobiological understanding of antidepressant treatment through an EEG-tailored computational model and provide a clinical avenue for personalized treatment of depression.

Major depressive disorder is associated with aberrant resting-state functional connectivity across multiple brain networks supporting emotion processing, executive function, and reward processing. The purpose of this study was to determine whether patterns of resting-state connectivity between brain regions predict differential outcome to antidepressant medication (sertraline) compared with placebo.Participants in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study underwent structural and resting-state functional MRI at baseline. Participants were then randomly assigned to receive either sertraline or placebo treatment for 8 weeks (N=279). A region of interest-based approach was utilized to compute functional connectivity between brain regions. Linear mixed-model intent-to-treat analyses were used to identify brain regions that moderated (i.e., differentially predicted) outcomes between the sertraline and placebo arms.Prediction of response to sertraline involved several within- and between-network connectivity patterns. In general, higher connectivity within the default mode network predicted better outcomes specifically for sertraline, as did greater between-network connectivity of the default mode and executive control networks. In contrast, both placebo and sertraline outcomes were predicted (in opposite directions) by between-network hippocampal connectivity.This study identified specific functional network-based moderators of treatment outcome involving brain networks known to be affected by major depression. Specifically, functional connectivity patterns of brain regions between and within networks appear to play an important role in identifying a favorable response for a drug treatment for major depressive disorder.

Major depressive disorder (MDD) may be associated with accelerated brain aging (higher brain age than chronological age). This report evaluated whether brain age is a clinically useful biomarker by checking its test-retest reliability using magnetic resonance imaging (MRI) scans acquired one week apart and by evaluating the association of accelerated brain aging with symptom severity and antidepressant treatment outcomes.Brain age was estimated in participants of Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study using T1-weighted structural MRI [MDD N=290; female N=192; healthy control (HC) N=39; female N=24]. Intraclass correlation coefficient (ICC) were used for baseline-to-week-1 test-retest reliability. Association of baseline Δ brain age (brain age minus chronological age) with Hamilton Depression Rating Scale (HAMD-17) and Concise Health Risk Tracking Self-Report (CHRT-SR) domains [impulsivity, suicide propensity (measures pessimism, helplessness, perceived lack of social support, and despair), and suicidal thoughts] were assessed at baseline (linear regression) and during 8-week-long treatment with either sertraline or placebo (repeated-measures mixed models).Mean (±standard deviation) baseline chronological age, brain age, and Δ brain age were 37.1±13.3, 40.6±13.1, and 3.1±6.1 years in MDD and 37.1±14.7, 38.4±12.9, and 0.6±5.5 years in HC groups, respectively. Test-retest reliability was high (ICC=0.98-1.00). Higher baseline Δ brain age in MDD group was associated with higher baseline impulsivity and suicide propensity, and predicted smaller baseline-to-week-8 reductions in HAMD-17, impulsivity, and suicide propensity with sertraline but not with placebo.Brain age is a reliable and potentially clinically useful biomarker that can prognosticate antidepressant treatment outcomes.

Evaluate whether early improvement in irritability predicts improvement in depression severity in a naturalistic sample of adolescents undergoing pharmacologic treatment for major depressive disorder.Adolescents (N = 161) aged 13-18 years with a moderate to severe depressive episode were enrolled. Outcome measures included the Children's Depression Rating Scale-Revised (CDRS-R), Quick Inventory of Depressive Symptomatology (QIDS-AGreater baseline to week-4 reduction in irritability was associated with lower levels of CDRS-R, QIDS-AThe single item evaluation of irritability reduced assessment reliability in the absence of validated measures of irritability.Early reduction in irritability is strongly associated with better outcomes in depressed youths, regardless of baseline depression severity. Further research is needed to quantify the burden of irritability, explore it as a tool for measurement-based care, and to develop targeted treatments for irritability.

Through delineating the struggles and challenges of Dalits in making of the Dalit middle class, this article seeks to argue that the struggle and aspiration of Dalits to live a dignified life and urban as a space of ‘liberation from caste’ represents a high point in making of the new Dalit middle class. However, existing literature about the Dalit middle class revolves around identity, provision of reservation in education, employment and cultural assertion, but many unfolded narratives of the Dalit middle class exist. This article attempts to reveal the struggle and challenges of the new Dalit middle class to achieve the status of the middle class. Keeping this in mind further, this article aims to explore the transformations in everyday life of the new Dalit middle class regarding consumer behaviour and lifestyle. Besides this, the article provides a detailed narrative of the new Dalit middle class and about their experience of caste and class in the city.

BACKGROUND: The brain circuitry of depression and anxiety/fear is well-established, involving regions such as the limbic system and prefrontal cortex. We expand prior literature by examining the extent to which four discrete factors of anxiety (immediate state anxiety, physiological/panic, neuroticism/worry, and agitation/restlessness) among depressed outpatients are associated with differential responses during reactivity to and regulation of emotional conflict. METHODS: A total of 172 subjects diagnosed with major depressive disorder underwent functional magnetic resonance imaging while performing an Emotional Stroop Task. Two main contrasts were examined using whole brain voxel wise analyses: emotional reactivity and emotion regulation. We also evaluated the association of these contrasts with the four aforementioned anxiety factors. RESULTS: During emotional reactivity, participants with higher immediate state anxiety showed potentiated activation in the rolandic operculum and insula, while individuals with higher levels of physiological/panic demonstrated decreased activation in the posterior cingulate. No significant results emerged for any of the four factors on emotion regulation. When re-analyzing these statistically-significant brain regions through analyses of a subsample with (n = 92) and without (n = 80) a current anxiety disorder, no significant associations occurred among those without an anxiety disorder. Among those with an anxiety disorder, results were similar to the full sample, except the posterior cingulate was associated with the neuroticism/worry factor. CONCLUSIONS: Divergent patterns of task-related brain activation across four discrete anxiety factors could be used to inform treatment decisions and target specific aspects of anxiety that involve intrinsic processing to attenuate overactive responses to emotional stimuli.

Diabetes has been linked to accelerated brain aging, i.e., neuroimaging-predicted age of brain is higher than chronological age. This report evaluated whether accelerated brain aging in diabetes is associated with higher levels of glycated hemoglobin (HbA1c) and increased mortality.Brain age in Dallas Heart Study (n = 1949) was estimated using T1-weighted magnetic resonance imaging (MRI) scans and a previously-published Gaussian Processes Regression model. Accelerated brain aging (adjusted Δ brain age) was computed as follows: (brain age adjusted for chronological age)-minus-(chronological age). Mortality data until 12/31/2016 were obtained from the National Death Index. Associations of adjusted Δ brain age with diabetes in full sample and with HbA1c in individuals with diabetes were evaluated. Proportion of association between diabetes and all-cause mortality that was accounted for by adjusted Δ brain age were evaluated with mediation analyses. Covariates included Framingham 10-year risk score, race/ethnicity, income, body mass index, and history of myocardial infarction.Diabetes was associated with] higher adjusted Δ brain age [estimate= 1.79; 95% confidence interval (CI): 0.889, 2.68]. Among those with diabetes, higher HbA1c (log-base-2-transformed) was associated with higher adjusted Δ brain age (estimate=3.88; 95% CI: 1.47, 6.30). Over a median follow-up of 97.5 months, 24/246 (9.8%) with diabetes and 63/1703 (3.7%) without diabetes died. Adjusted Δ brain age accounted for 65.3 (95% CI: 39.3, 100.0)% of the association between diabetes and all-cause mortality.Accelerated brain aging may be related to poor glycemic control in diabetes and partly account for the association between diabetes and all-cause mortality.

Background Seltorexant, a selective antagonist of human orexin-2 receptors, demonstrated antidepressant effects in a previous exploratory study in patients with major depressive disorder (MDD). Methods To replicate and extend this observation, a double-blind, adaptive dose-finding study was performed in patients with MDD who had an inadequate response to 1–3 selective serotonin/serotonin-norepinephrine reuptake inhibitors in the current episode. Patients were randomized (2:1:1) to placebo or seltorexant (20 mg or 40 mg) once-daily, administered adjunctively to the antidepressant the patient had been receiving at screening. After an interim analysis (6 weeks post-randomization of 160th patient), newly recruited patients randomly received (3:3:1) placebo or seltorexant 10 mg or 20 mg; the 40-mg dose was no longer assigned. Patients were stratified by baseline Insomnia Severity Index (ISI) scores (ISI ≥ 15 vs