Shifting From Best Practice to Standard Practice: Implementing Measurement-Based Care in Health Systems.

There is a high prevalence of untreated depression in adults and youth observed at the population level in the United States, and many who would benefit from treatment do not receive it. One proposed effort to increase access to care is the use of measurement-based care (MBC; repeated use of symptom measures for screening and treatment guidance) by primary care physicians to treat non-complex cases of depression. MBC has been shown to improve patient outcomes compared to care as usual, but there are barriers that need to be addressed at the health system level for effective implementation to occur. Herein we provide an overview of MBC and detail benefits and barriers of MBC implementation. Relevant considerations and guidance for implementing MBC are presented, and a case example of a health system implementing MBC is included. Though issues of reimbursement, limited human and technological resources, and resistance to systemic change are barriers to implementing MBC, effective strategies exist to overcome these barriers. In addition to helping health systems align with changes to value-based care models, effective implementation of MBC can likely improve patient outcomes and result in net financial benefits.

Extended observation of reduced methamphetamine use with combined naltrexone plus bupropion in the ADAPT-2 trial.

BACKGROUND AND AIMS: 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 This study reports on the previously unpublished stage 2 MA use in participants randomized at stage 1 to receive NTX + BUPN through both stages compared with those assigned to placebo. DESIGN: This is a secondary analysis of the US National Institute on Drug Abuse (NIDA) ADAPT-2 network trial. SETTING: The parent ADAPT-2 trial was carried out across multiple NIDA Clinical Trials Network (CTN) sites in the United States. PARTICIPANTS: This analysis includes 403 people with MA use disorder who participated in the ADAPT-2 CTN trial. INTERVENTION AND COMPARATOR: NTX + BUPN was compared with placebo over the course of the trial. MEASUREMENT: 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. FINDINGS: 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. CONCLUSION: 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.

Active suicidal ideation associated with dysfunction in default mode network using resting-state EEG and functional MRI - Findings from the T-RAD Study.

Suicide in youth and young adults is a serious public health problem. However, the biological mechanisms of suicidal ideation (SI) remain poorly understood. The primary goal of these analyses was to identify the connectome profile of suicidal ideation using resting state electroencephalography (EEG). We evaluated the neurocircuitry of SI in a sample of youths and young adults (aged 10-26 years, n = 111) with current or past diagnoses of either a depressive disorder or bipolar disorder who were enrolled in the Texas Resilience Against Depression Study (T-RAD). Neurocircuitry was analyzed using orthogonalized power envelope connectivity computed from resting state EEG. Suicidal ideation was assessed with the 3-item Suicidal Thoughts factor of the Concise Health Risk Tracking self-report scale. The statistical pipeline involved dimension reduction using principal component analysis, and the association of neuroimaging data with SI using regularized canonical correlation analysis. From the original 111 participants and the correlation matrix of 4950 EEG connectivity pairs in each band (alpha, beta, theta), dimension reduction generated 1305 EEG connectivity pairs in the theta band, 2337 EEG pairs in the alpha band, and 914 EEG connectivity pairs in the beta band. Overall, SI was consistently involved with dysfunction of the default mode network (DMN). This report provides preliminary evidence of DMN dysfunction associated with active suicidal ideation in adolescents. Using EEG using power envelopes to compute connectivity moves us closer to using neurocircuit dysfunction in the clinical setting to identify suicidal ideation.

Effects of esketamine nasal spray on depressive symptom severity in adults with treatment-resistant depression and associations between the Montgomery-Åsberg Depression Rating Scale and the 9-item Patient Health Questionnaire.

OBJECTIVE: To examine the effect of esketamine nasal spray (ESK) plus newly initiated oral antidepressant (OAD) versus OAD plus placebo nasal spray (PBO) on the association between Montgomery-Åsberg Depression Rating Scale (MADRS) and 9-item Patient Health Questionnaire (PHQ-9) scores in adults with treatment-resistant depression (TRD). METHODS: Data from TRANSFORM-1 and TRANSFORM-2 (two similarly designed, randomized, active-controlled TRD studies) and SUSTAIN-1 (relapse prevention study) were analyzed. Group differences for mean changes in PHQ-9 total score from baseline were compared using analysis of covariance. Associations between MADRS and PHQ-9 total scores from TRANSFORM-1/TRANSFORM-2 were assessed using simple parametric, nonparametric, and multiple regression models. RESULTS: In TRANSFORM-1/TRANSFORM-2 (ESK + OAD, n = 343; OAD + PBO, n = 222), baseline PHQ-9 mean scores were 20.4 for ESK + OAD and 20.6 for OAD + PBO (severe depression). At day 28, significant group differences were observed in least squares mean change (SE) in PHQ-9 scores from baseline (-12.8 [0.46] vs -10.3 [0.53], P < .001) and in clinically substantial change in PHQ-9 scores (≥6 points; 77.1% vs 64%, P < .001) in ESK + OAD and OAD + PBO groups, respectively. A nonlinear relationship between MADRS and PHQ-9 was observed; total scores demonstrated increased correlation over time. In SUSTAIN-1, 57.3% of patients receiving ESK + OAD (n = 89) versus 44.2% receiving OAD + PBO (n = 86) retained remission status (PHQ-9 score ≤4) at maintenance treatment end point (P = .044). CONCLUSIONS: In adults with TRD, ESK + OAD significantly improved severity of depressive symptoms, and more patients achieved clinically meaningful changes in depressive symptoms based on PHQ-9, versus OAD + PBO. PHQ-9 outcomes were consistent with those of clinician-rated MADRS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02417064, NCT02418585, NCT02493868.

Optimizing Antidepressant Efficacy: Multimodal Neuroimaging Biomarkers for Prediction of Treatment Response.

Major depressive disorder (MDD) is a common and often severe condition that profoundly diminishes quality of life for individuals across ages and demographic groups. Unfortunately, current antidepressant and psychotherapeutic treatments exhibit limited efficacy and unsatisfactory response rates in a substantial number of patients. The development of effective therapies for MDD is hindered by the insufficiently understood heterogeneity within the disorder and its elusive underlying mechanisms. To address these challenges, we present a target-oriented multimodal fusion framework that robustly predicts antidepressant response by integrating structural and functional connectivity data (sertraline: R2 = 0.31; placebo: R2 = 0.22). Through the model, we identify multimodal neuroimaging biomarkers of antidepressant response and observe that sertraline and placebo show distinct predictive patterns. We further decompose the overall predictive patterns into constitutive network constellations with generalizable structural-functional co-variation, which exhibit treatment-specific association with personality traits and behavioral/cognitive task performance. Our innovative and interpretable multimodal framework provides novel insights into the intricate neuropsychopharmacology of antidepressant treatment and paves the way for advances in precision medicine and development of more targeted antidepressant therapeutics.

Sociodemographic and patient reported outcomes by racial and ethnicity status among participants in a randomized controlled trial for methamphetamine use disorder.

Background: There has been a significant increase in methamphetamine use and methamphetamine use disorder (Meth UD) in the United States, with evolving racial and ethnic differences. Objectives: This secondary analysis explored racial and ethnic differences in baseline sociodemographic and clinical characteristics as well as treatment effects on a measure of substance use recovery, depression symptoms, and methamphetamine craving among participants in a pharmacotherapy trial for Meth UD. Methods: The ADAPT-2 trial (ClinicalTrials.gov number, NCT03078075; N=403; 69% male) was a multisite, 12-week randomized, double-blind, trial that employed a two-stage sequential parallel design to evaluate the efficacy of combination naltrexone (NTX) and oral bupropion (BUP) vs. placebo for Meth UD. Treatment effect was calculated as the weighted mean change in outcomes in the NTX-BUP minus placebo group across the two stages of treatment. Results: Of the 403 participants in the ADAPT-2 trial, the majority (65%) reported non-Hispanic White, while 14%, 11% and 10% reported Hispanic, non-Hispanic Black, and non-Hispanic other racial and ethnic categories respectively. At baseline non-Hispanic Black participants reported less severe indicators of methamphetamine use than non-Hispanic White. Treatment effects for recovery, depression symptoms and methamphetamine cravings did not significantly differ by race and ethnicity. Conclusions: Although we found racial and ethnic differences at baseline, our findings did not show racial and ethnic differences in treatment effects of NTX-BUP on recovery, depression symptoms and methamphetamine cravings. However, our findings also highlight the need to expand representation of racial and ethnic minority groups in future trials.

Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial.

Further research is needed to help improve both the standard of care and the outcome for patients with treatment-resistant depression. A particularly critical evidence gap exists with respect to whether pharmacological or non-pharmacological augmentation is superior to antidepressant switch, or vice-versa. The objective of this study was to compare the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine XR (or duloxetine for those not eligible to receive venlafaxine) for treatment-resistant depression. In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years (SD 15.3)) with treatment-resistant depression were assigned in a 1:1:1 fashion to treatment with either of these three interventions; 235 subjects completed the study. 260 randomized subjects with at least one post-baseline Montgomery-Asberg Depression Rating (MADRS) assessment were included in the analysis. Repetitive transcranial magnetic stimulation (score change (standard error (se)) = -17.39 (1.3) (p = 0.015) but not aripiprazole augmentation (score change (se) = -14.9 (1.1) (p = 0.069) was superior to switch (score change (se) = -13.22 (1.1)) on the MADRS. Aripiprazole (mean change (se) = -37.79 (2.9) (p = 0.003) but not repetitive transcranial magnetic stimulation augmentation (mean change (se) = -42.96 (3.6) (p = 0.031) was superior to switch (mean change (se) = -34.45 (3.0)) on the symptoms of depression questionnaire. Repetitive transcranial magnetic stimulation augmentation was shown to be more effective than switching antidepressants in treatment-resistant depression on the study primary measure. In light of these findings, clinicians should consider repetitive transcranial magnetic stimulation augmentation early-on for treatment-resistant depression.Trial registration: ClinicalTrials.gov, NCT02977299.

Problematic substance use in depressed adolescents: Prevalence and clinical correlates.

Background: Substance use among adolescents is common and associated with significant consequences, including depression. Adolescents can experience myriad problems related to early onset substance use and depression, making further understanding of this comorbidity necessary. Method: Participants were a subset from a large-scale performance improvement project and consisted of adolescents aged 12-18 who screened positive for depression during their routine medical or psychiatric appointment and who then completed the substance use assessment Car, Relax, Alone, Forget, Friends, Trouble Version 2.1 (CRAFFT). Participants with problematic substance use had a CRAFFT score ≥2. Results: A total of 621 participants were included in this study, and 105 (16.9%) reported problematic substance use. Compared with participants without problematic substance use, those with problematic use were more likely to have moderate to severe depression and anxiety, as well as significantly higher irritability, impulsivity, suicidal propensity, and suicidal thoughts scores. Controlling for age at screening, sex, race, and ethnicity, problematic substance use remained a significant predictor of depression severity, impulsivity, suicidal propensity, and suicidal thoughts. Limitations: Participants were from a large, metropolitan area of the Southwest United States who must have screened positive for depression, so results may not generalize. Because all participants were underage, they may have been wary in responding to the substance use assessment accurately. Conclusions: By using a large, diverse sample in a real-world clinical setting, findings strengthen the association between problematic substance use and depression and depression-associated symptoms among adolescents, highlighting the need for early detection and universal depression screening.

Integration of Measurement-Based Care for Youth Depression and Suicidality Using VitalSign6.

Depression and suicidality are prevalent in youth and are associated with a range of negative outcomes. The current study aimed to evaluate a measurement-based care (MBC) software (VitalSign6) tool to improve the screening and treatment of depression and suicidality in youth aged 8-17 years within a rural, underserved population. To assess for depression and suicidality, the Patient Health Questionnaire-2 was administered as an initial screen, and the Patient Health Questionnaire-9 Modified for Adolescents (PHQ-9-A) was administered if the initial screen was positive. Data were collected at medical clinics over one year, and descriptive statistics and t-tests or Wilcoxon-Mann-Whitney tests were conducted. A total of 1,984 youth were initially screened (mean age of 13 years; 51.6% female); 24.2% screened positive for depression, and 14.9% endorsed suicidality. Of those who screened positive, the mean PHQ-9-A score was 12.8; 66.9% had PHQ-9-A scores in the moderate to severe range, and 44.2% endorsed suicidality. Almost half of the youth who screened positive for depression had at least one follow-up assessment, and about one quarter achieved remission 4 months after initial screening. Adolescents (12-17 years) had higher PHQ-9-A scores, higher suicidality, and more follow-up assessments than younger youth (8-11 years). Younger youth had higher rates of remission. The widespread use of MBC was feasible in this setting. It is important to utilize MBC to identify and treat youth with depression and suicidality and to do so in younger populations to improve their trajectory over time; VitalSign6 is one tool to help achieve these goals.

Characterizing Measurement-Based Care in the Texas Youth Depression and Suicide Research Network (TX-YDSRN).

Integration of measurement-based care (MBC) into clinical practice has shown promise in improving treatment outcomes for depression. Yet, without a gold standard measure of MBC, assessing fidelity to the MBC model across various clinical settings is difficult. A central goal of the Texas Youth Depression and Suicide Research Network (TX-YDSRN) was to characterize MBC across the state of Texas through the development of a standardized tool to assess the use of MBC strategies when assessing depression, anxiety, side effects, and treatment adherence. A chart review of clinical visits indicated standardized depression measures (71.2%) and anxiety measures (64%) were being utilized across sites. The use of standardized measures to assess medication adherence and side effects was limited to less than six percent for both, with the majority utilizing clinical interviews to assess adherence and side effects; yet medication was changed in nearly half. Rates of utilization of standardized measures for participants with multiple MBC forms were similar to those who only provided one form.

The magnitude and sustainability of treatment benefit of zuranolone on function and well-being as assessed by the SF-36 in adult patients with MDD and PPD: An integrated analysis of 4 randomized clinical trials.

BACKGROUND: Major depressive disorder (MDD) and postpartum depression (PPD) are disabling conditions. This integrated analysis of MDD and PPD clinical trials investigated the impact of zuranolone-a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and neuroactive steroid under investigation for adults with MDD and approved as an oral, once-daily, 14-day treatment course for adults with PPD in the US-on health-related quality of life, including functioning and well-being, as assessed using the 36-item Short Form Health Survey V2 (SF-36). METHODS: Integrated data from 3 MDD (201B, MOUNTAIN, WATERFALL) and 1 PPD trial (ROBIN) for individual SF-36 domains were compared for zuranolone (30- and 50-mg) vs placebo at Day (D)15 and D42. Comparisons between zuranolone responders (≥50 % reduction from baseline in 17-item Hamilton Depression Rating Scale total score) and nonresponders were assessed. RESULTS: Overall, 1003 patients were included (zuranolone, n = 504; placebo, n = 499). Significant differences in change from baseline (CFB) to D15 for patients in zuranolone vs placebo groups were observed in 6/8 domains; changes were sustained or improved at D42, with significant CFB differences for all 8 domains. Zuranolone responders had significantly higher CFB scores vs nonresponders for all domains at D15 and D42 (p < 0.001). LIMITATIONS: Two zuranolone doses were integrated across populations of 2 disease states with potential differences in functioning, comorbidities, and patient demographics. All p-values presented are nominal. CONCLUSIONS: Integrated data across 4 zuranolone clinical trials showed improvements in functioning and well-being across all SF-36 domains. Benefits persisted after completion of treatment course at D42.

Treatment of Adolescent Depression: Comparison of Psychiatric and Pediatric Settings at an Academic Medical Center Using the VitalSign6 Application.

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.

Brain ventricle and choroid plexus morphology as predictor of treatment response in major depression: Findings from the EMBARC study.

Recent observations suggest a role of the volume of the cerebral ventricle volume, corpus callosum (CC) segment volume, in particular that of the central-anterior part, and choroid plexus (CP) volume for treatment resistance of major depressive disorder (MDD). An increased CP volume has been associated with increased inflammatory activity and changes in the structure of the ventricles and corpus callosum. We attempt to replicate and confirm that these imaging markers are associated with clinical outcome in subjects from the EMBARC study, as implied by a recent pilot study. The EMBARC study is a placebo controlled randomized study comparing sertraline vs. placebo in patients with MDD to identify biological markers of therapy resistance. Association of baseline volumes of the lateral ventricles (LVV), choroid plexus volume (CPV) and volume of segments of the CC with treatment response after 4 weeks treatment was evaluated. 171 subjects (61 male, 110 female) completed the 4 week assessments; gender and age were taken into account for this analyses. As previously reported, no treatment effect of sertraline vs. placebo was observed, therefore the study characterized prognostic markers of response in the pooled population. Change in depression severity was identified by the ratio of the Hamilton-Depression rating scale 17 (HAMD-17) at week 4 divided by the HAMD-17 at baseline (HAMD-17 ratio). Volumes of the lateral ventricles and choroid plexi were positively correlated with the HAMD-17 ratio, indication worse outcome with larger ventricles and choroid plexus volumes, whereas the volume of the central-anterior corpus callosum was negatively correlated with the HAMD-17 ratio. Responders (n = 54) had significantly smaller volumes of the lateral ventricles and CP compared to non-responders (n = 117), whereas the volume of mid-anterior CC was significantly larger compared to non-responders (n = 117), confirming our previous findings. In an exploratory way associations between enlarged LVV and CPV and signs of lipid dysregulation were observed. In conclusion, we confirmed that volumes of lateral ventricles, choroid plexi and the mid-anterior corpus callosum are associated with clinical improvement of depression and may be indicators of metabolic/inflammatory activity.

The clinical presentation of major depressive disorder in youth with co-occurring obsessive-compulsive disorder.

BACKGROUND: Major depressive disorder (MDD) is common in youth and among the most frequent comorbid disorders in pediatric obsessive-compulsive disorder (OCD), but it is unclear whether the presence of OCD affects the symptom presentation of MDD in youth. METHODS: A sample of youth with OCD and MDD (n = 124) and a sample of youth with MDD but no OCD (n = 673) completed the Patient Health Questionnaire for Adolescents (PHQ-A). The overall and symptom-level presentation of MDD were examined using group comparisons and network analysis. RESULTS: Youth with MDD and OCD, compared to those with MDD and no OCD, had more severe MDD (Cohen's d = 0.39) and more reported moderate to severe depression (75 % vs 61 %). When accounting for demographic variables and the overall severity of MDD, those with comorbid OCD reported lower levels of anhedonia and more severe difficulties with psychomotor retardation/agitation. No significant differences in the interconnections among symptoms emerged. LIMITATIONS: Data were cross-sectional and self-reported, gold standard diagnostic tools were not used to assess OCD, and the sample size for the group with MDD and OCD was relatively small yielding low statistical power for network analysis. CONCLUSIONS: Youth with MDD and OCD have more severe MDD than those with MDD and no OCD and they experience more psychomotor issues and less anhedonia, which may relate to the behavioral activation characteristic of OCD.

Psychometric properties of the GAD-7 and PROMIS-Anxiety-4a among youth with depression and suicidality: Results from the Texas youth depression and suicide research network.

There is a tremendous need for brief, valid, and free assessments of anxiety in child mental healthcare. The goal of this study was to determine the psychometric properties of two such measures, the GAD-7 and PROMIS-Anxiety-4a, in 1000 children, adolescents, and young adults (8-20 years-old) with depression and/or suicidality. The GAD-7, the PROMIS-Anxiety-4a, and other validated assessments of anxiety, physical functioning, and psychiatric diagnoses were completed. Confirmatory factor analyses showed an acceptable fit for a single factor in both measures via all indices but the RMSEA. They demonstrated measurement invariance across pre-adolescents (8-12 years-old) and adolescents and emerging adults (13-20 years-old), though scalar invariance was not observed for the GAD-7. Both measures showed strong convergent validity, GAD-7: r = 0.68; PROMIS-Anxiety-4a: r = 0.75, divergent validity with a measure of physical function, GAD-7: r = -0.24; PROMIS-Anxiety-4a: r = -0.28, good internal consistency, ω = 0.89 for both, and high test-retest reliability, GAD-7: r = 0.69; PROMIS-Anxiety-4a: r = 0.71. Both measures also showed acceptable sensitivity and specificity in detecting the presence of any anxiety disorder, GAD-7 cut-off score of 10: AUC = 0.75; PROMIS-Anxiety-4a cutoff score of 12: AUC = 0.79. The GAD-7 correlated similarly with the Screen for Child Anxiety Related Disorders total score and generalized anxiety subscale, and also showed similar diagnostic sensitivity and specificity when used to detect the presence of any anxiety disorder vs. generalized anxiety disorder specifically. Results suggest that both of these brief, publicly available instruments are valid and reliable assessments of anxiety among youth in treatment for depression and/or suicidality.

Linking trauma to mental health in the statewide Texas Youth Depression and Suicide Research Network (TX-YDSRN).

Rates of youth depression and suicide are rising worldwide and represent public health crises. The present study examined the relationship between trauma history and symptoms of depression, suicidal ideation, and anxiety among suicidal and depressed youth. A diverse group of 1000 8-20-year-olds enrolled in the statewide Texas Youth Depression and Suicide Research Network (TX-YDSRN) reported their trauma history (Traumatic Events Screening Inventory for Children) and symptoms of depression (Patient Health Questionnaire for adolescents; PHQ-A), anxiety (Generalized Anxiety Disorder scale; GAD-7), and suicidality (Concise Health Risk Tracking scale; CHRT-SR). Nearly half of the sample reported exposure to multiple categories of traumatic experiences. Number of trauma exposure categories significantly predicted PHQ-A and GAD-7 scores. Exposure to interpersonal trauma and to sexual trauma were significantly associated with PHQ-A, GAD-7, and CHRT-SR scores. The number of trauma exposure categories was associated with increased levels of anxiety and depression; however, only exposure to interpersonal or sexual trauma was associated with more suicidality. Clinicians should assess trauma exposure in patients seeking psychiatric care, especially for interpersonal and sexual trauma, which may be predictive of increased risk for suicidality in depressed youth. Future work should disentangle the effects of specific trauma types from multiple trauma exposure.

Data-driven subgrouping of youths with depression reveals that resilience is associated with higher physical functioning despite high symptom burden in the Texas Youth Depression and Suicide Research Network (TX-YDSRN).

BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS) measure, which assesses past week status of seven domains (physical function mobility, anxiety, depressive symptoms, fatigue, peer relationships, pain interference, and pain intensity), represents a new paradigm using patient-reported outcomes. We used a data-driven approach with PROMIS to identify subgroups of youths receiving depression treatment. METHODS: Youths (n = 721) enrolled in the Texas Youth Depression and Suicide Research Network who completed the PROMIS were analyzed. Latent class analyses (LCAs) identified subgroups and compared their baseline clinical/sociodemographic features. RESULTS: Compared to population norms, our sample had worse than average physical function, anxiety, depression, fatigue, and pain interference. Using LCA, four subgroups were identified: 1) lower symptom severity and higher physical functioning (14.6 %); 2) higher symptom burden, higher pain interference/intensity, and lower physical functioning (52.7 %); 3) higher symptom burden, higher pain interference/intensity, but with higher physical functioning (9.2 %); and 4) higher symptom burden, but lower physical functioning and pain interference/intensity (23.6 %). Group 3 demonstrated higher resilience than Group 2. In contrast, Group 2 had higher anxiety than Group 4. LIMITATIONS: Individuals may have different symptom profiles due to the observational nature of the study. Replication of these subgroups may be difficult, as future samples may differ in these characteristics. Further work may demonstrate the stability of these groups. CONCLUSIONS: A data-driven analysis identified a small but significant subgroup with high physical functioning despite high symptom burden and pain, and this group reported higher resilience. Resilience-enhancing interventions may help improve functional outcomes in depressed youth.

Features of immunometabolic depression as predictors of antidepressant treatment outcomes: pooled analysis of four clinical trials.

BACKGROUND: Profiling patients on a proposed 'immunometabolic depression' (IMD) dimension, described as a cluster of atypical depressive symptoms related to energy regulation and immunometabolic dysregulations, may optimise personalised treatment. AIMS: To test the hypothesis that baseline IMD features predict poorer treatment outcomes with antidepressants. METHOD: Data on 2551 individuals with depression across the iSPOT-D (n = 967), CO-MED (n = 665), GENDEP (n = 773) and EMBARC (n = 146) clinical trials were used. Predictors included baseline severity of atypical energy-related symptoms (AES), body mass index (BMI) and C-reactive protein levels (CRP, three trials only) separately and aggregated into an IMD index. Mixed models on the primary outcome (change in depressive symptom severity) and logistic regressions on secondary outcomes (response and remission) were conducted for the individual trial data-sets and pooled using random-effects meta-analyses. RESULTS: Although AES severity and BMI did not predict changes in depressive symptom severity, higher baseline CRP predicted smaller reductions in depressive symptoms (n = 376, ßpooled = 0.06, P = 0.049, 95% CI 0.0001-0.12, I2 = 3.61%); this was also found for an IMD index combining these features (n = 372, ßpooled = 0.12, s.e. = 0.12, P = 0.031, 95% CI 0.01-0.22, I2= 23.91%), with a higher - but still small - effect size compared with CRP. Confining analyses to selective serotonin reuptake inhibitor users indicated larger effects of CRP (ßpooled = 0.16) and the IMD index (ßpooled = 0.20). Baseline IMD features, both separately and combined, did not predict response or remission. CONCLUSIONS: Depressive symptoms of people with more IMD features improved less when treated with antidepressants. However, clinical relevance is limited owing to small effect sizes in inconsistent associations. Whether these patients would benefit more from treatments targeting immunometabolic pathways remains to be investigated.