Neural substrates of emotional conflict with anxiety in major depressive disorder: Findings from the Establishing Moderators and biosignatures of Antidepressant Response in Clinical Care (EMBARC) randomized controlled trial.

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.

Psychometric properties of the Generalized Anxiety Disorder 7-item scale in youth: Screening in a primary care sample.

BACKGROUND: Anxiety disorders in youth are frequently underdiagnosed and untreated, partly due to a lack of screening in primary care. The Generalized Anxiety Disorder 7-item (GAD-7) scale is a brief self-report measure designed to screen for anxiety in primary care settings. However, little is known about the psychometrics of this scale with adolescents. METHODS: Participants included 579 youth age 11 to 17 years who received screening for depression in a primary care setting through a web-based application, VitalSign6, over a 4-year period. Psychometric analyses were completed based on classical test theory (CTT) and item response theory (IRT). RESULTS: Using CTT and IRT methods, the GAD-7 has a unidimensional structure with good psychometric properties. In addition, the IRT analysis demonstrates that items 1 and 2 are strongly associated with the total score, and thus are good choices as a 2-item screening tool. Convergent validity was demonstrated, with high correlations between the GAD-7 and other measures of anxiety, and discriminant validity was also demonstrated, with low correlations to measures of other psychological states. CONCLUSIONS: This psychometric evaluation of the GAD-7 provides support for the utility of this measure with adolescents. The GAD-2 is a good estimate of GAD-7 total score.

Dorsolateral Prefrontal Cortex and Subcallosal Cingulate Connectivity Show Preferential Antidepressant Response in Major Depressive Disorder.

BACKGROUND: Major depressive disorder is associated with abnormal connectivity across emotion and reward circuits as well as other established circuits that may negatively impact treatment response. The goal of this study was to perform an exploratory reanalysis of archival data from a clinical trial to identify moderators of treatment outcome of sertraline over placebo. METHODS: EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study participants completed magnetic resonance imaging before randomization to either sertraline or placebo for 8 weeks (n = 279). Seed-based functional connectivity was computed using 4 bilateral seeds (2 spheres defined bilaterally): amygdala, dorsolateral prefrontal cortex (DLPFC), subcallosal cingulate cortex, and ventral striatum. Functional connectivity maps were generated, principal component analysis was performed, linear mixed effects models were used to determine moderators of treatment outcome, and post hoc analyses were used to determine level of connectivity (low and high, -1 and +1 SD from the mean) that was most sensitive to improved depression severity (baseline to week 8) based on treatment. RESULTS: Greater mean reduction in the 17-item Hamilton Rating Scale for Depression score by 8 weeks occurred with sertraline relative to placebo when connectivity in the DLPFC was low (3-way interaction test, p = .05). Conditional on low connectivity in the DLPFC and subcallosal cingulate cortex and high connectivity in the ventral striatum and amygdala, there was on average a 4.8-point greater reduction in the 17-item Hamilton Rating Scale for Depression score with sertraline relative to placebo (p = .003). CONCLUSIONS: The level of functional connectivity seeded in both the DLPFC and the subcallosal cingulate cortex networks may play an important role in identifying a favorable response to sertraline over placebo.

Discovery and replication of cerebral blood flow differences in major depressive disorder.

Major depressive disorder (MDD) is a serious, heterogeneous disorder accompanied by brain-related changes, many of which are still to be discovered or refined. Arterial spin labeling (ASL) is a neuroimaging technique used to measure cerebral blood flow (CBF; perfusion) to understand brain function and detect differences among groups. CBF differences have been detected in MDD, and may reveal biosignatures of disease-state. The current work aimed to discover and replicate differences in CBF between MDD participants and healthy controls (HC) as part of the EMBARC study. Participants underwent neuroimaging at baseline, prior to starting study medication, to investigate biosignatures in MDD. Relative CBF (rCBF) was calculated and compared between 106 MDD and 36 HC EMBARC participants (whole-brain Discovery); and 58 MDD EMBARC participants and 58 HC from the DLBS study (region-of-interest Replication). Both analyses revealed reduced rCBF in the right parahippocampus, thalamus, fusiform and middle temporal gyri, as well as the left and right insula, for those with MDD relative to HC. Both samples also revealed increased rCBF in MDD relative to HC in both the left and right inferior parietal lobule, including the supramarginal and angular gyri. Cingulate and prefrontal regions did not fully replicate. Lastly, significant associations were detected between rCBF in replicated regions and clinical measures of MDD chronicity. These results (1) provide reliable evidence for ASL in detecting differences in perfusion for multiple brain regions thought to be important in MDD, and (2) highlight the potential role of using perfusion as a biosignature of MDD.

Effect of Intrinsic Patterns of Functional Brain Connectivity in Moderating Antidepressant Treatment Response in Major Depression.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A Structured Approach to Detecting and Treating Depression in Primary Care: VitalSign6 Project.

PURPOSE: This report describes outcomes of an ongoing quality-improvement project (VitalSign6) in a large US metropolitan area to improve recognition, treatment, and outcomes of depressed patients in 16 primary care clinics (6 charity clinics, 6 federally qualified health care centers, 2 private clinics serving low-income populations, and 2 private clinics serving patients with either Medicare or private insurance). METHODS: Inclusion in this retrospective analysis was restricted to the first 25,000 patients (aged ≥12 years) screened with the 2-item Patient Health Questionnaire (PHQ-2) in the aforementioned quality-improvement project. Further evaluations with self-reports and clinician assessments were recorded for those with positive screen (PHQ-2 >2). Data collected from August 2014 though November 2016 were available at 3 levels: (1) initial PHQ-2 (n = 25,000), (2) positive screen (n = 4,325), and (3) clinician-diagnosed depressive disorder with 18 or more weeks of enrollment (n = 2,160). RESULTS: Overall, 17.3% (4,325/25,000) of patients screened positive for depression. Of positive screens, 56.1% (2,426/4,325) had clinician-diagnosed depressive disorder. Of those enrolled for 18 or more weeks, 64.8% were started on measurement-based pharmacotherapy and 8.9% referred externally. Of the 1,400 patients started on pharmacotherapy, 45.5%, 30.2%, 12.6%, and 11.6% had 0, 1, 2, and 3 or more follow-up visits, respectively. Remission rates were 20.3% (86/423), 31.6% (56/177), and 41.7% (68/163) for those with 1, 2, and 3 or more follow-up visits, respectively. Baseline characteristics associated with higher attrition were: non-white, positive drug-abuse screen, lower depression/anxiety symptom severity, and younger age. CONCLUSION: Although remission rates are high in those with 3 or more follow-up visits after routine screening and treatment of depression, attrition from care is a significant issue adversely affecting outcomes.

Cerebral Blood Perfusion Predicts Response to Sertraline versus Placebo for Major Depressive Disorder in the EMBARC Trial.

BACKGROUND: Major Depressive Disorder (MDD) has been associated with brain-related changes. However, biomarkers have yet to be defined that could "accurately" identify antidepressant-responsive patterns and reduce the trial-and-error process in treatment selection. Cerebral blood perfusion, as measured by Arterial Spin Labelling (ASL), has been used to understand resting-state brain function, detect abnormalities in MDD, and could serve as a marker for treatment selection. As part of a larger trial to identify predictors of treatment outcome, the current investigation aimed to identify perfusion predictors of treatment response in MDD. METHODS: For this secondary analysis, participants include 231 individuals with MDD from the EMBARC study, a randomised, placebo-controlled trial investigating clinical, behavioural, and biological predictors of antidepressant response. Participants received sertraline (n = 114) or placebo (n = 117) and response was monitored for 8 weeks. Pre-treatment neuroimaging was completed, including ASL. A whole-brain, voxel-wise linear mixed-effects model was conducted to identify brain regions in which perfusion levels differentially predict (moderate) treatment response. Clinical effectiveness of perfusion moderators was investigated by composite moderator analysis and remission rates. Composite moderator analysis combined the effect of individual perfusion moderators and identified which contribute to sertraline or placebo as the "preferred" treatment. Remission rates were calculated for participants "accurately" treated based on the composite moderator (lucky) versus "inaccurately" treated (unlucky). FINDINGS: Perfusion levels in multiple brain regions differentially predicted improvement with sertraline over placebo. Of these regions, perfusion in the putamen and anterior insula, inferior temporal gyrus, fusiform, parahippocampus, inferior parietal lobule, and orbital frontal gyrus contributed to sertraline response. Remission rates increased from 37% for all those who received sertraline to 53% for those who were lucky to have received it and sertraline was their perfusion-preferred treatment. INTERPRETATION: This large study showed that perfusion patterns in brain regions involved with reward, salience, affective, and default mode processing moderate treatment response favouring sertraline over placebo. Accurately matching patients with defined perfusion patterns could significantly increase remission rates. FUNDING: National Institute of Mental Health, the Hersh Foundation, and the Center for Depression Research and Clinical Care, Peter O'Donnell Brain Institute at UT Southwestern Medical Center.Trial Registration.Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMARC) Registration Number: NCT01407094 (https://clinicaltrials.gov/ct2/show/NCT01407094).

VitalSign6: A Primary Care First (PCP-First) Model for Universal Screening and Measurement-Based Care for Depression.

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.

VitalSign: Screening, Diagnosis, and Treatment of Depression for Adolescents Presenting to Pediatric Primary and Specialty Care Settings.

Depression in youth is a critical public health concern. Nearly 13% of adolescents have experienced a depressive episode within the last year,1 and suicide is the second leading cause of death among 15- to 24-year-olds.2 Depression's negative impact spans several domains of functioning, leading to long-term effects on development.3 Recognizing the magnitude of the crisis, renewed guidelines by the US Preventive Services Taskforce and the American Academy of Pediatrics suggest that pediatric primary care providers become more active in the screening, diagnosis, and treatment of depression.4,5 Primary care settings provide optimal opportunities to identify and treat depression, while reducing stigma and barriers surrounding mental health, particularly given the limited availability and cost of psychiatric specialists. Although providers cite difficulties, including insufficient appointment time, inadequate training, discomfort addressing mental health disorders, and stigma, the management of depressed patients is feasible and efficacious in primary care.6-8 Several cost-efficient and easy-to-use depression screening tools are readily available and can be used alongside clinical interviews to diagnose and initiate treatment. In the following letter, we examine the feasibility of implementing a program focused on supporting pediatric providers in screening, diagnosing, and initiating depression treatment in youth.

Anxiety and anhedonia in depression: Associations with neuroticism and cognitive control.

BACKGROUND: Despite the fact that higher levels of anxiety and anhedonia in Major Depressive Disorder (MDD) are linked to poorer treatment outcomes, mechanisms contributing to these clinical presentations remain unclear. Neuroticism, impaired cognitive control, and blunted reward learning may be critical processes involved in MDD and may help to explain symptoms of anxiety and anhedonia. METHODS: Using baseline data from patients with early-onset MDD (N = 296) in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) trial, we conducted a path analysis to model relationships between neuroticism, cognitive control, and reward learning to levels of anxiety and anhedonia. RESULTS: Neuroticism was positively associated with both anhedonia (standardized coefficient = 0.26, p < .001) and anxiety (standardized coefficient = 0.40, p < .001). Cognitive control was negatively associated with anxiety (standardized coefficient = -0.18, p < .05). Reward learning was not significantly associated with either anxiety or anhedonia. LIMITATIONS: Extraneous variables not included in the model may have even more influence in explaining symptoms of anxiety and anhedonia. Restricted range in these variables may have attenuated some of the hypothesized relationships. Most important, because this was a cross-sectional analysis in a currently depressed sample, we cannot draw any causal conclusions without experimental and longitudinal data. CONCLUSIONS: These cross-sectional findings suggest that neuroticism may contribute to anxiety and anhedonia in patients with early onset and either chronic or recurrent MDD, while enhanced cognitive control may protect against anxiety.

The Concise Health Risk Tracking-Self Report: Psychometrics within a placebo-controlled antidepressant trial among depressed outpatients.

BACKGROUND/AIMS: While substantial prior research has evaluated the psychometric properties of the 12-item Concise Health Risk Tracking-Self Report (CHRT-SR12), a measure of suicide propensity and suicidal thoughts, no prior research has investigated its factor structure, sensitivity to change over time, and other psychometric properties in a placebo-controlled trial of antidepressant medication, nor determined whether symptoms change throughout treatment. METHODS: Participants in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study ( n=278) provided data to evaluate the factor structure and sensitivity to change over time of the CHRT-SR12 through eight weeks of a clinical trial in which participants received either placebo or antidepressant medication (sertraline). RESULTS/OUTCOMES: Factor analysis confirmed two factors: propensity (comprised of first-order factors including pessimism, helplessness, social support, and despair) and suicidal thoughts. Internal consistency (α's ranged from 0.69-0.92) and external validity were both acceptable, with the total score and propensity factor scores significantly correlated with total scores and single-item suicidal-thoughts scores on the self-report Quick Inventory of Depressive Symptoms and the clinician-rated 17-item Hamilton Rating Scale for Depression. Through analyzing CHRT-SR12 changes over eight treatment weeks, the total score and both the factors decreased regardless of baseline suicidal thoughts. Change in clinician-rated suicidal thoughts was reflected by change in both the total score and propensity factor score. CONCLUSIONS/INTERPRETATION: These results confirm the reliability, validity, and applicability of the CHRT-SR12 to a placebo-controlled clinical trial of depressed outpatients receiving antidepressant medication.

Toward a very brief quality of life enjoyment and Satisfaction Questionnaire.

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.

The Concise Health Risk Tracking Self-Report (CHRT-SR) assessment of suicidality in depressed outpatients: A psychometric evaluation.

BACKGROUND: The 12-item Concise Health Risk Tracking Self-Report (CHRT-SR12 ) is a brief, self-report measure that systematically assesses both suicidal thinking and associated thoughts that may indicate the propensity for suicidal acts. It can be used as a tool to both assess risk and guide treatment interventions targeting associated cognitions. METHODS: This report used acute treatment data from a clinically representative sample of outpatients with nonpsychotic major depressive disorder (N = 665) participating in the Combining Medications to Enhance Depression Outcomes trial, who received up to 12 weeks of escitalopram, escitalopram plus bupropion SR, or venlafaxine XR plus mirtazapine. Outcome assessors and patients were masked to treatment. RESULTS: Factor analysis of CHRT-SR12 confirmed that the 12 items have higher order structure with two subscales (Propensity, Suicidal Thoughts) and a total score. Internal consistencies were acceptable for both subscales and total score. All three scales were modestly correlated with overall depression severity (r = 0.54 to r = 0.21) and highly discriminating among patients grouped by suicide item ratings on three different depressive symptom ratings. The three scales also distinguished change over the acute phase treatment for those with different levels of baseline suicidal ideation (measured by 30-item Inventory of Depressive Symptomatology (item 18) and for those with change in suicidal ideation (baseline to last visit). CONCLUSIONS: The CHRT-SR12 has good to excellent psychometric properties and is sensitive to change in suicidal thinking and propensity toward suicidal behavior in outpatients with major depressive disorder. It allows for the monitoring of thoughts and feelings associated with increased suicidal risk as well as levels of thoughts about suicide.

Improving the identification and treatment of depression in low-income primary care clinics: a qualitative study of providers in the VitalSign6 program.

QUALITY PROBLEM: Despite its global burden and prevalence, Major Depressive Disorder often goes undetected and untreated, and is particularly pervasive in the primary care setting. INITIAL ASSESSMENT: One in four Texans lack health insurance, and people with behavioral health disorders are disproportionately affected. It is possible to provide high-quality depression treatment in primary care settings with outcomes equal to those provided by specialty care. The Center for Depression Research and Clinical Care offered an opportunity to transform service delivery practices in underserved primary care practices to improve quality, health status, patient experience and coordination. CHOICE OF SOLUTION: A point-of-care, web-based, self-report based software program, VitalSign6, was developed to provide universal depression screening in primary care practices and assist providers in monitoring and treating patients' symptoms using principles of Measurement-Based Care. IMPLEMENTATION: Implementation included a multi-faceted training program designed to build confidence and competence in participating clinics' medical providers and staff as well as ongoing performance improvement delivered by the VitalSign6 team. EVALUATION: Primary care providers (N = 11) were interviewed, using a semi-structured interview guide, with a focus on barriers and challenges to full integration, perceptions of the most/least valuable aspects of the program, and the program's impact on knowledge, attitudes and behaviors about depression screening and treatment. LESSONS LEARNED: More efficient technology is needed to reduce time wasted, as is training to reduce stigma and correct misconceptions about antidepressant medications. Provider buy-in is essential. CONCLUSIONS: Despite barriers, VitalSign6 increased knowledge, changed attitudes and enhanced providers' depression screening and treatment skills over time.

A Novel Strategy to Identify Placebo Responders: Prediction Index of Clinical and Biological Markers in the EMBARC Trial.

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.

Do baseline sub-threshold hypomanic symptoms affect acute-phase antidepressant outcome in outpatients with major depressive disorder? Preliminary findings from the randomized CO-MED trial.

Sub-threshold hypomanic symptoms are common in major depressive disorder. This study evaluated the prevalence, the clinical and sociodemographic correlates, and the overall and differential effects of the presence/absence of sub-threshold hypomanic symptoms at baseline on acute-phase treatment outcomes with bupropion-plus-escitalopram combination, escitalopram monotherapy, and venlafaxine-plus-mirtazapine combination. Combining medications to enhance depression outcomes (CO-MED) trial participants (n = 665) were designated as sub-threshold hypomanic symptoms present (Altman Self-Rating Mania Scale score (ASRM) ≥ 1) or absent (ASRM = 0) and compared on clinical and sociodemographic features and remission rates. Participants with sub-threshold hypomanic symptoms (n = 335/665, 50.4%) were more likely to be black and non-Hispanic, have comorbid medical and psychiatric disorders, experience longer index episodes, and report lower depression severity and psychosocial impairment. Intent-to-treat remission rates were lower overall (absent = 42.7%, present = 34.0%, p = 0.02), with escitalopram monotherapy (absent = 45.8%, present = 31.6%, p = 0.03), and with venlafaxine-XR-plus-mirtazapine combination (absent = 44.4%, present = 30.1%, p = 0.03) but not with bupropion-plus-escitalopram combination (absent = 37.7%, present = 40.0%, p = 0.73). Participants without sub-threshold hypomanic symptoms were more likely to remit than those with such symptoms overall [odds ratio (OR) = 1.49], with escitalopram monotherapy (OR = 1.71), and with venlafaxine-plus-mirtazapine combination (OR = 1.97) but not with bupropion-plus-escitalopram combination (OR = 0.96), even after controlling for baseline depression severity, psychosocial impairment, and number of comorbid psychiatric disorders. Sub-threshold hypomanic symptoms (found in about 50% of patients in this report) were associated with lower remission rates with escitalopram monotherapy and with venlafaxine-plus-mirtazapine combination but not with the bupropion-plus-escitalopram combination.

Characterizing anxiety subtypes and the relationship to behavioral phenotyping in major depression: Results from the EMBARC study.

The current study aimed to characterize the multifaceted nature of anxiety in patients with major depression by evaluating distinct anxiety factors. We then related these derived anxiety factors to performance on a Flanker Task of cognitive control, in order to further validate these factors. Data were collected from 195 patients with nonpsychotic chronic or recurrent major depression or dysthymic disorder. At baseline, participants completed self-report measures of anxiety, depression, and other related symptoms (mania, suicidality) and clinicians administered a structured diagnostic interview and the Hamilton Rating Scale for Depression, including anxiety/somatization items. Four discrete factors (State Anxiety, Panic, Neuroticism/Worry, and Restlessness/Agitation) emerged, with high degrees of internal consistency. Discriminant and convergent validity analyses also yielded findings in the expected direction. Furthermore, the neuroticism/worry factor was associated with Flanker Task interference, such that individuals higher on neuroticism/worry responded more incorrectly (yet faster) to incongruent vs. congruent trials whereas individuals higher on the fear/panic factor responded more slowly, with no accuracy effect, to the Flanker Task stimuli. These results parse anxiety into four distinct factors that encompass physiological, psychological, and cognitive components of anxiety. While state anxiety, panic and neuroticism/worry are related to existing measures of anxiety, the Restlessness/Agitation factor appears to be a unique measure of general anxious arousal. Furthermore, two factors were independently validated through the Flanker Task. These results suggest that these anxiety domains have distinct behavioral profiles and could have differential responses to distinct treatments.

Psychometric properties of the concise health risk tracking (CHRT) in adolescents with suicidality.

BACKGROUND: Several self-report rating scales have been developed to assess suicidal ideation, yet few examine other factors related to increased suicidal risk, and even fewer have been validated in both adolescents and adults. We evaluate the 14-item Concise Health Risk Tracking - Self Report (CHRT-SR), a measure previously validated in adults, in a sample of adolescents at risk for suicide. METHOD: Data are from a retrospective chart review of adolescents treated in an intensive outpatient program for youth with severe suicidality. Teens completed the CHRT-SR and Quick Inventory of Depressive Symptomatology - Adolescents (QIDS-A) at baseline and discharge. The CHRT-SR was evaluated to determine the factor validity, internal consistency, construct validity, and sensitivity to change. RESULTS: Adolescents (n = 271) completed the CHRT-SR prior to treatment, and 231 completed the CHRT-SR at discharge. Three factors were identified with excellent model fit: Propensity, Impulsivity, and Suicidal Thoughts. Internal consistency reliability coefficients were good-to-excellent for the total score and all three factors at baseline (a = 0.774-0.915) and exit (a = 0.849-0.941). The total score and all three factors significantly correlated with overall depression severity and suicidal ideation as rated by teens and parent (p = .704-0.756, all p < .001). The CHRT-SR was sensitive to change, with moderate to large effect sizes (Cohen's d = 0.599-1.062). LIMITATIONS: Study limitations include generalizability, lack of a control group, and retrospective data from a sample of opportunity. CONCLUSIONS: The CHRT-SR is a reliable and valid measure for examining severity of suicidal thoughts and associated risk factors, and is sensitive to change following an intervention in adolescents.

A psychometric evaluation of the Concise Health Risk Tracking Self-Report (CHRT-SR)- a measure of suicidality-in patients with stimulant use disorder.

Stimulant use disorders are both common and associated with suicidal ideation and attempts. The psychometric properties of the 12-item Concise Health Risk Tracking Scale Self-Report (CHRT-SR), a measure that was created to assess suicidal thinking and several factors associated with a propensity to act, has been established in persons with mood disorders. This is a secondary analysis to assess the CHRT-SR in 302 stimulant abusing patients that had participated in a clinical trial. A confirmatory factor analysis (CFA) was conducted to assess the factor validity of the 12-item CHRT-SR model with a second-order Propensity factor. The CHRT-SR total score and 2 factor scores (Propensity and Suicidal Thoughts) demonstrated acceptable internal consistency and test-retest reliabilities. These two subscales and the total score were modestly but significantly associated with measures of depression and life satisfaction, demonstrating construct validity. Two additional items assessing Impulsivity were also analyzed, and demonstrated acceptable internal consistency, test-retest reliability, and construct validity. The CHRT-SR appears to be a reliable and valid tool to assess suicidality in persons with stimulant use disorder.

Psychometrics of the Self-Report Concise Associated Symptoms Tracking Scale (CAST-SR): Results From the STRIDE (CTN-0037) Study.

OBJECTIVE: The self-report Concise Associated Symptoms Tracking Scale (CAST-SR) was developed to track mania, irritability, anxiety, panic, and insomnia symptoms among depressed outpatients receiving antidepressant medication. Given the overlap between these domains, depression, and stimulant use disorders, we reexamined CAST-SR psychometrics in a novel sample: individuals with stimulant use disorder receiving aerobic exercise or health education interventions. METHODS: Using the subsample of stimulant-dependent (following DSM-IV criteria) individuals prescribed antidepressants (N = 124) from the multisite Stimulant Reduction Intervention Using Dosed Exercise (CTN-0037) trial (total sample N = 302), conducted July 2010 to February 2013, we analyzed CAST-SR data collected at the first assessment after participant's discharge from residential treatment. We also evaluated the convergent/discriminant validity of the CAST-SR with several self-report questionnaires. RESULTS: Confirmatory factor analysis revealed a 12-item measure composed of 4 factors: irritability, anxiety, panic, and insomnia. This factor structure loaded only in participants prescribed antidepressant medication, not in those who were not prescribed antidepressants. These results replicate the original CAST-SR factor structure, except for the mania factor, which failed to load. Internal consistency was high (α = 0.92 for total scale and α = 0.78-0.89 for the 4 factors), and convergent validity was established, especially for the insomnia and irritability factors, alongside the total score with depressive symptoms, insomnia, quality of life, suicide risk, and physical health measures. CONCLUSIONS: These results demonstrate the factor structure, reliability, and validity of the CAST-SR in a novel population of only individuals with stimulant use disorders receiving both exercise/health education interventions and antidepressant medication. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01141608.