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Objective Among individual depressive symptoms, anhedonia has been reliably associated with activation of the innate immune response. However, it is unclear whether this association extends to T cell cytokines and if gender differentially affects this association. Method Concentrations of T (IL-17, T-helper (Th) 1- and Th2-) and non-T cell cytokines were measured in plasma using the Bioplex Pro™ human cytokine multiplex kit in Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants who provided plasma at baseline (n = 166). Anhedonia was measured with three items of the clinician-rated Inventory of Depressive Symptomatology and depression severity (minus anhedonia item) was measured with Quick Inventory of Depression Severity Self-Report version (modified-QIDS-SR). Separate generalized linear models for anhedonia and modified-QIDS-SR as dependent variables were conducted with IL-17, Th1-, Th2-, and non-T cell- cytokines as primary independent variables and gender, body mass index (BMI), and age as covariates. Exploratory analyses included gender-by-biomarker interactions. Results Higher levels of IL-17 (p = 0.032), Th1- (p = 0.002), Th2-(p = 0.001) and non-T-(p = 0.009) cell markers were associated with greater severity of anhedonia controlling for BMI, age, and gender. Gender also had a significant main effect on anhedonia, however, there was a significant gender by immune marker interaction only for IL-17 (p = 0.050). Anhedonia severity increased with higher IL-17 in males (r = 0.42, p = 0.003) but not in females (r = 0.09, p = 0.336). Only non-T cell markers were associated with the modified-QIDS-SR, and there were no significant gender-specific associations with this variable. Conclusions T and non-T cell-related inflammatory markers were associated with greater severity of anhedonia, while gender moderated the association of IL-17 with anhedonia in patients with major depressive disorder. [ABSTRACT FROM AUTHOR]

Background: One in three clinical trial patients with major depressive disorder report symptomatic improvement with placebo. Strategies to mitigate the effect of placebo responses have focused on modifying study design with variable success. Identifying and excluding or controlling for individuals with a high likelihood of responding to placebo may improve clinical trial efficiency and avoid unnecessary medication trials.Methods: Participants included those assigned to the placebo arm (n = 141) of the Establishing Moderators and Biosignatures for Antidepressant Response in Clinical Care (EMBARC) trial. The elastic net was used to evaluate 283 baseline clinical, behavioral, imaging, and electrophysiological variables to identify the most robust yet parsimonious features that predicted depression severity at the end of the double-blind 8-week trial. Variables retained in at least 50% of the 100 imputed data sets were used in a Bayesian multiple linear regression model to simultaneously predict the probabilities of response and remission.Results: Lower baseline depression severity, younger age, absence of melancholic features or history of physical abuse, less anxious arousal, less anhedonia, less neuroticism, and higher average theta current density in the rostral anterior cingulate predicted a higher likelihood of improvement with placebo. The Bayesian model predicted remission and response with an actionable degree of accuracy (both AUC > 0.73). An interactive calculator was developed predicting the likelihood of placebo response at the individual level.Conclusion: Easy-to-measure clinical, behavioral, and electrophysiological assessments can be used to identify placebo responders with a high degree of accuracy. Development of this calculator based on these findings can be used to identify potential placebo responders. [ABSTRACT FROM AUTHOR]

Background: We report on the psychometric properties of the 16-item Concise Associated Symptom Tracking Scale self-report scale and its clinical utility. Methods: The 5-domain (irritability, anxiety, mania, insomnia, and panic) structure of Concise Associated Symptom Tracking Scale was validated with confirmatory factor analysis in Combining Medications to Enhance Depression Outcomes trial participants at baseline (n = 664). Correlations with other clinical measures were used for convergent and divergent validity. In participants with at least one postbaseline visit (n = 630), worsening in each Concise Associated Symptom Tracking Scale domain was defined as =1.28 SD increase from baseline for each visit (weeks 1, 2, 4, and 6) only. Worsening in any domain (except mania) was defined as overall worsening. Association of domain-specific and overall worsening with remission was tested with logistic regression analyses. Results: The 5-domain structure had adequate model fit on confirmatory factor analysis (GFI = 0.93, CFI = 0.89, and RMSEA = 0.07). Scores on anxiety, panic, insomnia, and mania significantly correlated with Hamilton Rating Scale for Depression anxiety subscale (rs = 0.27), Psychiatric Diagnostic Screening Questionnaire-panic scale (rs = 0.35), sum of 3 Quick Inventory of Depressive Symptomatology Self-Report insomnia items (rs = 0.55), and Altman Self-Rating Mania scale (rs = 0.41), respectively. From baseline to week 6, 5.2%, 7.5%, 47.6%, 15.6%, 6.2%, and 27.6% participants (n = 630) experienced irritability, anxiety, mania, insomnia, panic, and overall worsening, respectively. Participants with overall worsening were less likely to remit (31.6%) than those without any worsening (43.9%; odds ratio = 0.53, 95% CI = 0.36, 0.78). Conclusion: The 16-item Concise Associated Symptom Tracking Scale self-report has acceptable psychometric properties. Clinically significant worsening of irritability, anxiety, insomnia, or panic with antidepressant treatment is associated with poorer outcomes. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a chronic condition that affects one in six adults in the US during their lifetime. The current practice of antidepressant medication prescription is a trial-and-error process. Additionally, over a third of patients with MDD fail to respond to two or more antidepressant treatments. There are no valid clinical markers to personalize currently available antidepressant medications, all of which have similar mechanisms targeting monoamine neurotransmission. The goal of this review is to summarize the recent findings of immune dysfunction in patients with MDD, the utility of inflammatory markers to personalize treatment selection, and the potential of targeting inflammation to develop novel antidepressant treatments. To personalize antidepressant prescription, a c-reactive protein (CRP)-matched treatment assignment can be rapidly implemented in clinical practice with point-of-care fingerstick tests. With this approach, 4.5 patients need to be treated for 1 additional remission as compared to a CRP-mismatched treatment assignment. Anti-cytokine treatments may be effective as novel antidepressants. Monoclonal antibodies against proinflammatory cytokines, such as interleukin 6, interleukin 17, and tumor necrosis factor α, have demonstrated antidepressant effects in patients with chronic inflammatory conditions who report significant depressive symptoms. Additional novel antidepressant strategies targeting inflammation include pharmaceutical agents that block the effect of systemic inflammation on the central nervous system. In conclusion, inflammatory markers offer the potential not only to personalize antidepressant prescription but also to guide the development of novel mechanistically-guided antidepressant treatments. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to determine whether a unique analytic approach - as a proof of concept - could identify individual depressed outpatients (using 30 baseline clinical and demographic variables) who are very likely (75% certain) to not benefit (NB) or to remit (R), accepting that without sufficient certainty, no prediction (NP) would be made. Methods: Patients from the Combining Medications to Enhance Depression Outcomes trial treated with escitalopram (S-CIT) + placebo (n=212) or S-CIT + bupropion-SR (n=206) were analyzed separately to assess replicability. For each treatment, the elastic net was used to identify subsets of predictive baseline measures for R and NB, separately. Two different equations that estimate the likelihood of remission and no benefit were developed for each patient. The ratio of these two numbers characterized likely outcomes for each patient. Results: The two treatment cells had comparable rates of remission (40%) and no benefit (22%). In S-CIT + bupropion-SR, 11 were predicted NB of which 82% were correct; 26 were predicted R - 85% correct (169 had NP). For S-CIT + placebo, 13 were predicted NB - 69% correct; 44 were predicted R - 75% correct (155 were NP). Overall, 94/418 (22%) patients were identified with a meaningful degree of certainty (69%-85% correct). Different variable sets with some overlap were predictive of remission and no benefit within and across treatments, despite comparable outcomes. Conclusion: In two separate analyses with two different treatments, this analytic approach - which is also applicable to pretreatment laboratory tests - identified a meaningful proportion (over 20%) of depressed patients for whom a treatment outcome was predicted with sufficient certainty that the clinician can elect to strongly recommend for or choose to avoid a particular treatment. Different persons seem to be remitting or not benefiting with these two different treatments. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) significantly impacts performance of both work- and nonwork-related routine daily activities. We have shown that work productivity is significantly impaired in employed MDD patients, but the extent of impairments in nonworkrelated routine activities and its association with antidepressant treatment outcomes has not been established. Materials and methods: Activity impairment was measured using the sixth item of Work Productivity and Activity Impairment Scale in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial (n=665). Published norms were used to define activity impairment levels. The relationship between activity impairment and baseline sociodemographic and clinical characteristics was evaluated along with changes in activity impairment and its relationship with other clinical outcomes such as symptom severity, function, and side effect burden. Remission status at 3 and 7 months was predicted based on week 6 activity impairment level. Results: Higher psychosocial and cognitive impairments and greater number of comorbid medical conditions were associated with greater activity impairment at baseline. Proportion of participants with severe activity impairment declined from 47.6% at baseline to 18.7% at 3 months, while mean activity impairment decreased from 57.1 at baseline to 32.8 at 3 months. During course of treatment, levels of activity impairment correlated most strongly with psychosocial function among measures of symptom severity, function, quality of life, and side effect burden. No or minimal activity impairment at week 6 was associated with two to three times higher rates of remission at 3 and 7 months as compared to moderate or severe activity impairment levels even after controlling for remission status at week 6 and select baseline variables. Conclusion: Depressed patients have high levels of nonwork-related activity impairment at baseline that improves significantly with treatment and independently predicts long-term clinical outcomes. Brief systematic assessment of activity impairment during the course of antidepressant treatment can help inform clinical decision-making. [ABSTRACT FROM AUTHOR]

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. • Participants with diabetes had older-appearing brain age than those without. • Poorer glycemic control was associated with more accelerated brain aging. • Accelerated brain aging accounted for association between diabetes and mortality. [ABSTRACT FROM AUTHOR]

The probabilistic reward task (PRT) has identified reward learning impairments in those with major depressive disorder (MDD), as well as anhedonia-specific reward learning impairments. However, attempts to validate the anhedonia-specific impairments have produced inconsistent findings. Thus, we seek to determine whether the Reward Behavior Disengagement (RBD), our proposed economic augmentation of PRT, differs between MDD participants and controls, and whether there is a level at which RBD is high enough for depressed participants to be considered objectively disengaged. Data were gathered as part of the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study, a double-blind, placebo-controlled clinical trial of antidepressant response. Participants included 195 individuals with moderate to severe MDD (Quick Inventory of Depressive Symptomatology (QIDS–SR) score ≥ 15), not in treatment for depression, and with complete PRT data. Healthy controls (n = 40) had no history of psychiatric illness, a QIDS–SR score < 8, and complete PRT data. Participants with MDD were treated with sertraline or placebo for 8 weeks (stage I of the EMBARC trial). RBD was applied to PRT data using discriminant analysis, and classified MDD participants as reward task engaged (n = 137) or reward task disengaged (n = 58), relative to controls. Reward task engaged/disengaged groups were compared on sociodemographic features, reward–behavior, and sertraline/placebo response (Hamilton Depression Rating Scale scores). Reward task disengaged MDD participants responded only to sertraline, whereas those who were reward task engaged responded to sertraline and placebo (F(1293) = 4.33, p = 0.038). Reward task engaged/disengaged groups did not differ otherwise. RBD was predictive of reward impairment in depressed patients and may have clinical utility in identifying patients who will benefit from antidepressants. [ABSTRACT FROM AUTHOR]

Abstract: Avascular necrosis of the femoral head is one of the most common skeletal complications among renal allograft recipients complaining of hip pain. While bilateral avascular necrosis is more frequent than the unilateral type, we report a case of unilateral avascular necrosis of the hip occurring post renal transplant recipient. Avascular necrosis was likely the result of steroid therapy. A well-tailored steroid therapy that prevents unjustified high doses and ‘pulsed doses’ while maintaining the optimum maintenance level of steroids is necessary. [Copyright &y& Elsevier]

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. • Deaths due to suicide have been increasing in the US. • Suicide and depression may be linked to immune dysfunction. • There is a need to identify potential markers of suicide behavior. • This study maps immune dysfunction to suicidal behavior in adolescents. [ABSTRACT FROM AUTHOR]

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 (HAMD 17) and response/remission rates by treatment group. Three subgroups were identified. Cluster-1 was characterized by overall hyper connectivity 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. [ABSTRACT FROM AUTHOR]

This paper analyses the context in which Special Economic Zones are promoted as an important route to economic growth and development in India. The process for the approval of these Special Economic Zones has been expedited by various provincial governments after a hasty policy and legislative decision undertaken by the central government with severe re-percussions on the lives and livelihoods of the affected people. The paper examines the basic features of the Special Economic Zone Act, the role of the government and corporate houses, and also the protest movement by political subjects against the legislative and executive initiatives under-taken by the state and its agencies. Drawing from testimonies of people, the paper examines the processes whereby state sponsored 'exceptional-ity' is being challenged through collective initiatives by political subjects. [ABSTRACT FROM AUTHOR]

The habenula-pancreas axis regulates the stimulatory effects of nicotine on blood glucose levels and may participate in the emergence of type 2 diabetes in human tobacco smokers. This secondary analysis of young adults from the Human Connectome Project (HCP-YA) evaluated whether smoking status links the relationship between habenular volume and glycated hemoglobin (HbA1c), a marker of long-term glycemic control. Habenula segmentation was performed using a fully-automated myelin content-based approach in HCP-YA participants and the results were inspected visually (n = 693; aged 22–37 years). A linear regression analysis was used with habenular volume as the dependent variable, the smoking-by-HbA1c interaction as the independent variable of interest, and age, gender, race, ethnicity, education, income, employment status, body mass index, and total gray matter volume as covariates. Habenula volume and HbA1c were similar in smokers and nonsmokers. There was a significant interaction effect (F (1, 673) = 5.03, p = 0.025) indicating that habenular volume was related to HbA1c in a manner that depended on smoking status. Among participants who were smokers (n = 120), higher HbA1c was associated with apparently larger habenular volume (β = 6.74, standard error=2.36, p = 0.005). No such association between habenular volume and HbA1c was noted among participants who were nonsmokers (n = 573). Blood glucose levels over an extended time period, reflected by HbA1c, were correlated with habenular volume in smokers, consistent with a relationship between the habenula and blood glucose homeostasis in smokers. Future studies are needed to evaluate how habenular function relates to glycemic control in smokers and nonsmokers. • Smoking-status modulated the link between habenular volume and glycated hemoglobin (HbA1c). • Higher HbA1c was associated with apparently larger habenular volume in smokers. • No association between HbA1c and habenular volume in nonsmokers. [ABSTRACT FROM AUTHOR]

• Interleukin 4 (IL-4) levels are lower in adolescents and young adults with depression and suicidality. • Other inflammation-related markers didn't differ in those with recent suicidality vs. healthy controls and those at-risk. • IL-4 levels were negatively correlated with self-reported depression severity. • Lower IL-4 levels were associated with higher autoantibody levels in an unrelated sample of depressed outpatients. Immune system dysfunction has been implicated in the pathophysiology of suicide behavior. Here, we conducted an exploratory analysis of immune profile differences of three groups of adolescents and young adults (ages 10–25 years): healthy controls (n = 39), at risk of major depressive disorder (MDD; at-risk, n = 33), and MDD with recent suicide behavior/ ideation (suicide behavior, n = 37). Plasma samples were assayed for chemokines and cytokines using Bio-Plex Pro Human Chemokine 40-plex assay. Log-transformed cytokine and chemokine levels were compared after controlling for age, gender, body mass index, race, ethnicity, and C-reactive protein (CRP) levels. In post-hoc analyses to understand the effect of dysregulated immune markers identified in this exploratory analysis, their association with autoantibodies was tested in an unrelated sample (n = 166). Only levels of interleukin 4 (IL-4) differed significantly among the three groups [false discovery rate (FDR) adjusted p = 0.0007]. Participants with suicide behavior had lower IL-4 [median = 16.8 pg/ml, interquartile range (IQR) = 7.9] levels than healthy controls (median = 29.1 pg/ml, IQR = 16.1, effect size [ES] = 1.30) and those at-risk (median = 24.4 pg/ml, IQR = 16.3, ES = 1.03). IL-4 levels were negatively correlated with depression severity (r= −0.38, p = 0.024). In an unrelated sample of outpatients with MDD, levels of IL-4 were negatively correlated (all FDR p < 0.05) with several autoantibodies [54/117 in total and 12/18 against innate immune markers]. Adolescent and young adult patients with recent suicide behavior exhibit lower IL-4 levels. One biological consequence of reduced IL-4 levels may be increased risk of autoimmunity. [ABSTRACT FROM AUTHOR]

Background and aims Design Setting Participants Intervention and comparator Measurement Findings Conclusion A 12‐week placebo‐controlled, sequential parallel Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder (ADAPT‐2) trial evaluated the effects of extended‐release injectable naltrexone plus extended‐release oral bupropion (NTX + BUPN) on methamphetamine (MA) use over two stages. This study reports on the previously unpublished stage 2 MA use in participants randomized at stage 1 to receive NTX + BUPN through both stages compared with those assigned to placebo.This is a secondary analysis of the US National Institute on Drug Abuse (NIDA) ADAPT‐2 network trial.The parent ADAPT‐2 trial was carried out across multiple NIDA Clinical Trials Network (CTN) sites in the United States.This analysis includes 403 people with MA use disorder who participated in the ADAPT‐2 CTN trial.NTX + BUPN was compared with placebo over the course of the trial.MA use was measured by urine drug screens conducted twice weekly for 12 weeks, then once in week 13 and once in week 16 post‐treatment follow‐up.Participants on NTX + BUPN in stage 1 showed an additional 9.2% increase [95% confidence interval (CI), 0.09%–17.9%, P = 0.038] during stage 2 in their probability of testing negative for MA, with a total increase of 27.1% (95% CI, 13.2%–41.1%, P < 0.001) over the full 12 weeks of treatment. In contrast, participants on placebo in both stages increased in probability of testing MA‐negative by a total of 11.4% (95% CI, 4.1%–18.6%, P = 0.002) over all 12 weeks. The 12‐week increase among participants on NTX + BUPN was significantly greater—by 15.8% (95% CI, 4.5%–27.0%, P = 0.006)—than the increase among those on placebo.For people with methamphetamine (MA) use disorder receiving treatment with extended‐release injectable naltrexone plus extended‐release oral bupropion (NTX + BUPN), continued treatment with NTX + BUPN after 6 weeks is associated with additional reductions in MA use up to 12 weeks. [ABSTRACT FROM AUTHOR]

Major depressive disorder affects one in five adults in the United States. While practice guidelines recommend universal screening for depression in primary care settings, clinical outcomes suffer in the absence of optimal models to manage those who screen positive for depression. The current practice of employing additional mental health professionals perpetuates the assumption that primary care providers (PCP) cannot effectively manage depression, which is not feasible, due to the added costs and shortage of mental health professionals. We have extended our previous work, which demonstrated similar treatment outcomes for depression in primary care and psychiatric settings, using measurement-based care (MBC) by developing a model, called Primary Care First (PCP-First), that empowers PCPs to effectively manage depression in their patients. This model incorporates health information technology tools, through an electronic health records (EHR) integrated web-application and facilitates the following five components: (1) Screening (2) diagnosis (3) treatment selection (4) treatment implementation and (5) treatment revision. We have implemented this model as part of a quality improvement project, called VitalSign6, and will measure its success using the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) framework. In this report, we provide the background and rationale of the PCP-First model and the operationalization of VitalSign6 project. [ABSTRACT FROM AUTHOR]

Background: Similar outcomes and remission rates have been found for the treatment of depression in adults in primary and psychiatric care settings. However, comparatively little is known about how pediatric depression is managed across different settings. This study aims to address this gap by comparing depression treatment in pediatric and psychiatric settings. We hypothesized that pediatric care settings would be more likely to treat individuals with lower depression severity and would select pharmacotherapy less frequently as a treatment option. Methods: Patients (n = 3498) were screened for depression at a children's hospital from May 2017 to May 2022 as part of the VitalSign6 project, a web-based application for depression management. The two-item patient health questionnaire (PHQ) was used for screening, and the data set contains patient-reported measures and provider-reported diagnoses and treatment selections at each clinic visit. Patients with nine-item PHQ (PHQ-9) scores ≥10 at baseline were included in the analysis to compare diagnosis and treatment recommendations between pediatric and psychiatric settings. Results: Among the 1323 patients who screened positive for depression, those in psychiatric settings had higher PHQ-9 scores (15.9 ± 5.0 vs. 12.1 ± 5.5; p < 0.0001). Patients with PHQ-9 ≥ 10 in psychiatric settings were more likely to be diagnosed with major depressive disorder (60.6% vs. 24.7%, p < 0.0001) and receive pharmacotherapy (54.8% vs. 6.6%) than those in pediatric settings. Pediatric setting patients were more likely to receive nonpharmacological treatment alone (36.3% vs. 4.3%) or an outside referral (27.7% vs. 5.7%). Remission rates did not significantly differ between the two settings. Conclusions: Youth in psychiatric settings are more likely to screen positive for depression and to have greater depression severity than those in pediatric settings. Both settings provide treatment recommendations for moderate-to-severe depression, but treatment types vary substantially. Yet, remission rates remain similar. Further research is needed to understand the nuances of treatment differences and their implications. [ABSTRACT FROM AUTHOR]

Objective: To identify data-driven subgroups in Major Depressive Disorder (MDD) in order to elucidate underlying neural correlates and determine if these subgroups have utility in predicting response to antidepressant versus placebo.Methods: Using 27 clinical measures at baseline of Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study, participants with MDD (n=244) were sub grouped using principal component (PC) analysis. Baseline-to-week-8 changes in depression severity with sertraline versus placebo were compared in these subgroups. Resting-state functional connectivity of these subgroups were compared to those of healthy controls (n=38).Results: Eight subgroups were identified from four PCs: (PC1) severity of depression-associated symptoms, (PC2) sub-threshold mania and anhedonia, (PC3) childhood trauma, medical comorbidities, and sexual dysfunction, and (PC4) personality traits of openness and agreeableness. Participants with high childhood trauma experienced greater improvement with sertraline (Cohen's d=0.87), whereas those with either higher levels of subthreshold hypomanic symptoms (Cohen's d=0.67) or with lower levels of agreeableness and openness experienced greater improvement with placebo (Cohen's d=0.71). Participants with high childhood trauma had greater connectivity between salience and dorsal attention networks, whereas those with higher levels of subthreshold hypomanic symptoms and lower levels of agreeableness and openness had greater connectivity within limbic network and that of visual network with hippocampus and dorsal attention network.Conclusion: Assessing history of childhood trauma, presence of subthreshold hypomanic symptoms and personality traits may help to identify subgroups of patients with MDD who respond differentially to sertraline or placebo and have distinct neural signatures. [ABSTRACT FROM AUTHOR]

Depression has a chronic and recurrent course often with early onset and is the leading cause of disability worldwide. In contrast to diagnoses for other conditions which rely on precise medical tests, the diagnosis of depression still focuses exclusively on symptom reports. As a result, heterogeneous patient groups are included under broad categories. Furthermore, in the absence of companion diagnostic tests, choosing specific treatments for patients remains imprecise with only one-third of patients entering remission with initial treatment, with others requiring multiple intervention steps to achieve remission. In addition to improving treatment outcomes, disease prevention is essential to reduce overall disease burden. Adolescence is a critical window where complex emotional, social, familial, and biological shifts may predispose to lifelong depression. Thus, personalized medicine, integrating individual variability in genes, brain function, and clinical phenotypes, can offer a comprehensive approach to provide precise diagnosis, novel drug development, optimal treatment assignment, and prevention of illness and its associated burden. Texas Resilience Against Depression study (T-RAD) encompasses two natural history, longitudinal (10 + years), prospective studies (D2K and RAD), each enrolling 2500 participants. The D2K study follows participants (ages 10 years and older) who have a current or past diagnosis of depression or bipolar disorder. The RAD study follows participants aged 10–24 years who are at risk for depression but not yet suffering from the disease. The T-RAD study will help to uncover the socio-demographic, lifestyle, clinical, psychological, and neurobiological factors that contribute to mood disorder onset, recurrence, progression, and differential treatment response. [ABSTRACT FROM AUTHOR]

Highlights • A unidimensional self-report (the Mini-Q-LES-Q) was constructed using 7 items selected from the 14-item Quality of Life, Enjoyment and Satisfaction Scale (short form) (Q-LES-Q SF) while capturing 83–94% of the variance in the Q-LES-Q-SF. • The Mini-Q-LES-Q has excellent psychometric properties, detects improvements in quality of life-satisfaction with acute-phase antidepressant medication treatment, as well as residual quality of life-satisfaction deficiencies even when depressive symptom control is optimal. • The Mini-Q-LES-Q, which captures over 80% of the variance of the 14-item version, may help clinicians decide when and whether to target this important clinical domain. Abstract Objective To develop and evaluate a new brief self-report measure of satisfaction/quality of life in depressed outpatients. Methods Using the Quality of Life Enjoyment and Satisfaction Questionnaire Short-Form (Q-LES-Q-SF) self-report from Step-1 (n = 2181) of the STAR*D trial, items were selected based on their magnitude of change with treatment and correlation with 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR 16). Psychometric analyses were conducted. Replication of scale performance was assessed with STAR*D Step-2 data (n = 250). Results The 7 items selected ("Mini-Q-LES-Q") rated satisfaction with work, household activities, social and family relations, leisure time activities, daily function and sense of well-being in the past week. This uni-dimensional scale captured 83–94% variance in Q-LES-Q-SF and had acceptable Item Response and Classical Test Theory characteristics. Baseline to exit percent changes in the Mini-Q-LES-Q and the QIDS-SR 16 were significantly, modestly related (r = -0.552) (Step-1) and replicated (r = -0.562) (Step-2). The Mini-Q-LES-Q detected the expected improvement in satisfaction/quality of life in acute treatment, yet also identified residual deficits expected in many at acute-phase exit. Limitations Population norms are yet undefined. Concurrent validity with detailed, well-validated scales that assess the seven Quality of Life domains incorporated in the Mini-Q-LES-Q remains unestablished. Sensitivity to symptom changes induced by psychotherapy or somatic therapies or sensitive to the effects of therapies aimed at enhancing quality of life enjoyment and function is unknown. Conclusion The 7-item Mini-Q-LES-Q self-report measure satisfaction/quality of life has acceptable psychometric properties, reflects change with depressive symptom reduction, and detects residual deficits in this key clinical outcome. [ABSTRACT FROM AUTHOR]

Objective: To develop and evaluate a new brief self-report measure of satisfaction/quality of life in depressed outpatients.Methods: Using the Quality of Life Enjoyment and Satisfaction Questionnaire Short-Form (Q-LES-Q-SF) self-report from Step-1 (n = 2181) of the STAR*D trial, items were selected based on their magnitude of change with treatment and correlation with 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Psychometric analyses were conducted. Replication of scale performance was assessed with STAR*D Step-2 data (n = 250).Results: The 7 items selected ("Mini-Q-LES-Q") rated satisfaction with work, household activities, social and family relations, leisure time activities, daily function and sense of well-being in the past week. This uni-dimensional scale captured 83-94% variance in Q-LES-Q-SF and had acceptable Item Response and Classical Test Theory characteristics. Baseline to exit percent changes in the Mini-Q-LES-Q and the QIDS-SR16 were significantly, modestly related (r = -0.552) (Step-1) and replicated (r = -0.562) (Step-2). The Mini-Q-LES-Q detected the expected improvement in satisfaction/quality of life in acute treatment, yet also identified residual deficits expected in many at acute-phase exit.Limitations: Population norms are yet undefined. Concurrent validity with detailed, well-validated scales that assess the seven Quality of Life domains incorporated in the Mini-Q-LES-Q remains unestablished. Sensitivity to symptom changes induced by psychotherapy or somatic therapies or sensitive to the effects of therapies aimed at enhancing quality of life enjoyment and function is unknown.Conclusion: The 7-item Mini-Q-LES-Q self-report measure satisfaction/quality of life has acceptable psychometric properties, reflects change with depressive symptom reduction, and detects residual deficits in this key clinical outcome. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Up to 15% of patients with major depressive disorder (MDD) attempt suicide and up to 2% complete suicide. This was a post-hoc analysis aimed to evaluate the risk of suicide ideation and behavior associated with adjunctive pimavanserin treatment in adults with MDD.Methods: CLARITY was a randomized, double-blind, placebo-controlled study in patients with MDD and an inadequate response to a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). For this post-hoc analysis, the primary endpoint was mean change from baseline for HAMD item 3 (suicide). The incidence of suicidal ideation or behavior was also assessed from the Columbia-Suicide Severity Rating Scale (C-SSRS) and reports of adverse events.Results: During Stage 1, LS mean change for HAMD Item 3 was reduced from baseline at each week with pimavanserin with a significant difference between pimavanserin and placebo at Week 3 (p=0.012, effect size: 0.431). At any post-baseline assessment, suicidal ideation on the C-SSRS was reported in 28 (18.1%) of patients with placebo and 9 (17.3%) with pimavanserin during Stage 1 and in 7 (20.7%) with placebo and 4 (13.8%) with pimavanserin during Stage 2. No events of suicidal behavior were observed with either placebo or pimavanserin.Limitations: The post hoc nature, exclusion of patients with any history of suicide from the primary study, and the small number of patients who demonstrated evidence of suicidal ideation.Conclusions: Adjunctive pimavanserin was not associated with an increase in suicidal ideation in patients with MDD. Further study is needed to verify these results. [ABSTRACT FROM AUTHOR]

Several self-report rating scales have been developed to assess suicidal ideation, yet most have limited utility in predicting future suicide attempts. This is particularly critical in adolescence, where suicide is the second leading cause of death. This study evaluated the Concise Health Risk Tracking Self-Report (CHRT-SR) as a prospective predictor of suicide attempts and events in high-risk adolescents enrolled in a suicide-prevention intensive outpatient program (IOP). Data were collected by retrospective chart review of adolescents treated in IOP for youth with severe suicidality. At baseline, youth completed the 14-item CHRT-SR (CHRT-SR 14), which assesses suicide risk based on 3 subscales: Propensity, Impulsivity, and Suicidal Thoughts. Two outcomes were assessed: actual suicide attempts and suicidal events (suicide attempt, inpatient hospitalization, or emergency department visit) during the IOP. Of the 251 adolescents who completed the baseline CHRT-SR 14 , 26 had a suicidal event during IOP (mean time in IOP: 5.4 ± 2.3 weeks), of whom 14 had an actual suicide attempt. Youth with any suicidal event had higher scores than those without an event on the CHRT-SR 14 Total (p =.005), Propensity (p =.008), and Suicidal Thoughts (p =.001) scales at baseline. Youth who made a suicide attempt had significantly higher scores than those without an event for the Total Score, Propensity, and Suicidal Thoughts subscales. CHRT-SR 14 Total Score of 28 had a sensitivity of 85.7% and specificity of 56.5% in predicting suicide attempts. A score of 22 predicted suicidal events, with a sensitivity of 80.8% and specificity of 40.9%. CHRT-SR 7 Total Score of 12 predicted suicide attempts, with a sensitivity of 85.7% and specificity of 53.4%. The CHRT-SR 14 self-report predicts suicide attempts and events with at least 80% sensitivity and acceptable specificity in adolescents at high-risk for suicide. • The CHRT-SR predicts suicide attempts with at least 80% sensitivity and 50% specificity in suicidal adolescents. • Findings are consistent with previous reports that the CHRT-SR predicted suicidal events in adults with Bipolar Disorder. • This is one of the first rating scales to predict future suicide attempts with acceptable sensitivity or specificity. [ABSTRACT FROM AUTHOR]