Development and Evaluation of a Pragmatic Measure of Adherence to Dialectical Behavior Therapy: The DBT Adherence Checklist for Individual Therapy.

This paper presents two studies conducted to develop and evaluate a new pragmatic measure of therapist adherence to Dialectical Behavior Therapy (DBT): the DBT Adherence Checklist for Individual Therapy (DBT AC-I). Study 1 used item response analysis to select items from the gold standard DBT Adherence Coding Scale (DBT ACS) using archival data from 1271 DBT sessions. Items were then iteratively refined based on feedback from 33 target end-users to ensure relevance, usability, and understandability. Study 2 examined the psychometric properties of the DBT AC-I as a therapist self-report and observer-rated measure in 100 sessions from 50 therapist-client dyads, while also evaluating predictors of therapist accuracy in self-rated adherence. When used as a therapist self-report measure, concordance between therapist and observer ratings was at least moderate (AC1 ≥ 0.41) for all DBT AC-I items but overall concordance (ICC = 0.09) as well as convergent (r = 0.05) and criterion validity (AUC = 0.54) with the DBT ACS were poor. Higher therapist accuracy was predicted by greater DBT knowledge and adherence as well as more severe client suicidal ideation. When used by trained observers, the DBT AC-I had excellent interrater reliability (ICC = 0.93), convergent validity (r = 0.90), and criterion validity (AUC = 0.94). While therapists' self-rated adherence on the DBT AC-I should not be assumed to reflect their actual adherence, some therapists may self-rate accurately. The DBT AC-I offers an effective and relatively efficient method of evaluating adherence to DBT when used by trained observers.

Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study.

BACKGROUND: Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors. METHODS: In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies. MEASUREMENTS AND MAIN RESULTS: An admission sTNFR1 concentration > 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration > 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level > 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor. CONCLUSIONS: Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials.

SCHOOL-RELATED OUTCOMES FROM A RANDOMIZED CONTROLLED TRIAL OF ADOLESCENT DEPRESSION PREVENTION PROGRAMS.

Previous research has demonstrated the effectiveness of school-based depression prevention programs in reducing depressive symptoms and improving functioning. This study examined whether these programs have positive effects on school-related outcomes. Students at 10 middle and high schools in New Jersey were randomized to weekly sessions of Interpersonal Psychotherapy - Adolescent Skills Training (IPT-AST) or group counseling (GC). Analyses examined whether there were intervention effects on participants' grades, attendance rates, and disciplinary outcomes over approximately one year post-intervention. Although there were no significant main effects of intervention condition, moderation analyses indicated more favorable effects of IPT-AST among certain higher-risk subgroups (e.g., those from low-income families). Participants who experienced meaningful improvement in their depressive symptoms had significantly more positive outcomes on overall grades than those who did not experience meaningful improvement, regardless of intervention condition. Further research is needed to clarify the effects of depression prevention programs on these school-related outcomes.

What changes when? The course of improvement during a stage-based treatment for suicidal and self-injuring women with borderline personality disorder and PTSD.

OBJECTIVE: Dialectical Behavior Therapy (DBT) with the DBT Prolonged Exposure (DBT PE) protocol is an integrated treatment for suicidal and self-injuring individuals with PTSD and borderline personality disorder (BPD) that occurs in three stages: Stage 1 targets behavioral dyscontrol, Stage 2 targets posttraumatic stress disorder (PTSD) via the DBT PE protocol, and Stage 3 addresses remaining problems. We evaluated the course of change in multiple outcomes across these three stages and compared them to changes found in DBT alone. METHOD: Participants were 38 women with BPD, PTSD and recent suicidal and/or non-suicidal self-injury. Data were collected weekly or bi-weekly to assess PTSD, BPD, global well-being, state dissociation, and urges to engage in problem behaviors. RESULTS: In DBT + DBT PE, there was a significant improvement in PTSD in Stage 2 and in PTSD, BPD, and state dissociation in Stage 3. Compared to DBT, DBT + DBT PE led to significantly higher global well-being and moderately, but non-significantly, lower PTSD and BPD in Stages 2 and/or 3. CONCLUSIONS: PTSD does not improve until it is directly targeted and changes in other comorbid problems occur after PTSD is treated. Adding the DBT PE protocol to DBT was associated with improvement rather than worsening of outcomes.

Predicting Change in an Integrated Dual Diagnosis Substance Abuse Intensive Outpatient Program.

Research on routine outcome monitoring in psychotherapy settings is plentiful but not without implementation obstacles. In fact, there is a relative dearth of real-time outcome monitoring in substance use treatment settings. Numerous barriers to the development and implementation of clinical decision support tools and outcome monitoring of substance use patients, including the need to establish expected trajectories of change and use of reliable change indices have been identified (Goodman, McKay, & DePhilippis, 2013 ). The current study was undertaken to develop expected trajectories of change and to demonstrate the treatment effectiveness of a dual diagnosis intensive outpatient program. The expected trajectories of change for days of substance use and depression scores were developed using predictive equation models from derivation samples and then applied to cross-validation samples. Predictive equations to monitor substance use were developed and validated for all patients and for only patients who were actively using substance at the time of admission, as well as to monitor severity of their depression symptom on a weekly basis. Validation of the equations was assessed through the use of Cohen's kappa (κ), receiver operating characteristic curves, reliable change index, and percentage improvement. Large effect sizes for reductions in substance use (Cohen's d = .76) and depressive symptoms (d = 1.10) are reported. The best predictive models we developed had absolute accuracy rates ranging from 95 to 100%. The findings from this study indicate that predictive equations for depressive symptoms and days of substance use can be derived and validated on dual diagnosis samples.

Predicting individual change during the course of treatment.

OBJECTIVE: An empirically derived prediction model was developed in a private practice setting to monitor on-track and off-track weekly treatment progress in an intensive outpatient program (IOP). METHOD: The predictive equation was derived as a function of the baseline measure and time. The formulae for the predictive equations were derived from two groups of psychiatric patients (N = 400 each) in an IOP diagnosed with major depression. Each equation was cross-validated between these two psychiatric IOP samples and a dual diagnosis sample (N = 198) using κ, the reliable change index (RCI), receiver operating characteristic curves, and Youden's J. RESULTS: Using varying RCI classifications, approximately 66-75% of both samples reliably improved, 23-24% were indeterminant, and only 1-3% deteriorated. Of patients identified as off-track, which included patients classified as indeterminant and deteriorated, 83% were correctly identified. Of those identified as on-track, 85% were correctly classified. Those identified as on-track (85%) are highly likely to respond to treatment as expected. CONCLUSIONS: The overall efficiency index (hit rate) for the correct classification of all patients was 85%. Implications for using this predictive model as a clinical support decision tool with relatively homogeneous populations in other practice settings are discussed.

Impact of prenatal maternal depression on gestational length: post hoc analysis of a randomized clinical trial.

Background: Shortened gestation is a leading cause of childhood morbidity and mortality with lifelong consequences for health. There is a need for public health initiatives on increasing gestational age at birth. Prenatal maternal depression is a pervasive health problem robustly linked via correlational and epidemiological studies to shortened gestational length. This proof-of-concept study tests the impact of reducing prenatal maternal depression on gestational length with analysis of a randomized clinical trial (RCT). Methods: Participants included 226 pregnant individuals enrolled into an RCT and assigned to receive either interpersonal psychotherapy (IPT) or enhanced usual care (EUC). Recruitment began in July 2017 and participants were enrolled August 10, 2017 to September, 8 2021. Depression diagnosis (Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; DSM 5) and symptoms (Edinburgh Postnatal Depression Scale and Symptom Checklist) were evaluated at baseline and longitudinally throughout gestation to characterize depression trajectories. Gestational dating was collected based on current guidelines via medical records. The primary outcome was gestational age at birth measured dichotomously (≥39 gestational weeks) and the secondary outcome was gestational age at birth measured continuously. Posthoc analyses were performed to test the effect of reducing prenatal maternal depression on gestational length. This trial is registered with ClinicalTrials.gov (NCT03011801). Findings: Steeper decreases in depression trajectories across gestation predicted later gestational age at birth, specifically an increase in the number of full-term babies born ≥39 gestational weeks (EPDS linear slopes: OR = 1.54, 95% CI 1.10-2.16; and SCL-20 linear slopes: OR = 1.67, 95% CI 1.16-2.42). Causal mediation analyses supported the hypothesis that participants assigned to IPT experienced greater reductions in depression symptom trajectories, which in turn, contributed to longer gestation. Supporting mediation, the natural indirect effect (NIE) showed that reduced depression trajectories resulting from intervention were associated with birth ≥39 gestational weeks (EPDS, OR = 1.65, 95% CI 1.02-2.66; SCL-20, OR = 1.85, 95% CI 1.16-2.97). Interpretation: We used a RCT design and found that reducing maternal depression across pregnancy was associated with lengthened gestation. Funding: This research was supported by the NIH (R01 HL155744, R01 MH109662, R21 MH124026, P50 MH096889).

Higher prenatal anxiety predicts lower neonatal hair cortisol.

BACKGROUND: Prenatal glucocorticoids are one of the most widely proposed prenatal programming mechanisms, yet few studies exist that measure fetal cortisol via neonatal hair. Neonatal hair provides a window into the fetal experience and represents cortisol accumulation in the third trimester of pregnancy. In the current study, we test the links between two types of anxiety over the course of gestation (pregnancy-related anxiety and general anxiety) with neonatal hair cortisol. METHOD: Pregnant individuals (N = 107) and their neonates (59.8% female) participated in the current study. Prenatal pregnancy-related anxiety and general anxiety were measured using the Pregnancy Related Anxiety Scale (PRAS) and the State-Trait Anxiety Inventory (STAI), in each trimester of pregnancy. Hierarchical linear modeling was used to model the intercept and slope of each type of anxiety over gestation. Neonatal hair samples were collected shortly after birth (Median days = 1.17, IQR = 0.75-2.00). RESULTS: Both higher pregnancy-related anxiety and general anxiety at the beginning of pregnancy and a flatter decline of pregnancy-related anxiety over gestation were associated with lower neonatal hair cortisol. After inclusion of gestational age at birth and parity as covariates, pregnancy-related anxiety (intercept: ß = -0.614, p =.012; slope: ß = -0.681, p =.006), but not general anxiety (intercept: ß = -0.389, p =.114; slope: ß = -0.302, p =.217) remained a significant predictor. Further, when both general and pregnancy-related anxiety were entered into the same model, only pregnancy-related anxiety (intercept and slope) were significant predictors of neonatal hair cortisol, indicating an association with pregnancy-related anxiety above and beyond general anxiety. CONCLUSION: Cortisol plays a central role in maturation of fetal organ systems, and at the end of gestation, higher cortisol has beneficial effects such as promoting fetal lung maturation. Further, lower maternal cortisol is linked to less optimal cognitive development and altered brain development. As maternal higher anxiety in early pregnancy and a flatter decrease over time are both associated with lower neonatal hair cortisol, maternal pregnancy-related anxiety could be a target of future intervention efforts.

Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia.

Recent molecular genetics studies implicate neuregulin 1 (NRG1) and its receptor erbB in the pathophysiology of schizophrenia. Among NRG1 receptors, erbB4 is of particular interest because of its crucial roles in neurodevelopment and in the modulation of N-methyl-D-aspartate (NMDA) receptor signaling. Here, using a new postmortem tissue-stimulation approach, we show a marked increase in NRG1-induced activation of erbB4 in the prefrontal cortex in schizophrenia. Levels of NRG1 and erbB4, however, did not differ between schizophrenia and control groups. To evaluate possible causes for this hyperactivation of erbB4 signaling, we examined the association of erbB4 with PSD-95 (postsynaptic density protein of 95 kDa), as this association has been shown to facilitate activation of erbB4. Schizophrenia subjects showed substantial increases in erbB4-PSD-95 interactions. We found that NRG1 stimulation suppresses NMDA receptor activation in the human prefrontal cortex, as previously reported in the rodent cortex. NRG1-induced suppression of NMDA receptor activation was more pronounced in schizophrenia subjects than in controls, consistent with enhanced NRG1-erbB4 signaling seen in this illness. Therefore, these findings suggest that enhanced NRG1 signaling may contribute to NMDA hypofunction in schizophrenia.

Seeking safety therapy for pathological gambling and PTSD: a pilot outcome study.

This pilot study evaluated Seeking Safety (SS) therapy for seven outpatients with current comorbid pathological gambling (PG) and posttraumatic stress disorder (PTSD). This represents the first treatment outcome study of this population, and included both genders and 29% minorities. We found significant improvements in: PTSD/trauma (the PTSD Checklist criterion B symptoms; the Trauma Symptom Inventory overall mean and subscales anxiety, dissociation, sexual abuse trauma index, sex problems; and the World Assumptions Scale benevolence subscale); gambling (the Gamblers Beliefs Questionnaire overall mean and subscales illusion of control); functioning (the Basis-32 overall mean and depression/anxiety subscale); psychopathology (the Brief Symptom Inventory overall mean and subscales anxiety and depression; and the Addiction Severity Index, ASI, psychiatric composite score); self-compassion (the Self-Compassion Scale overall mean and subscales isolation, overidentified, and self-judgment); and helping alliance (the Helping Alliance Questionnaire overall mean). One variable indicated worsening (employment composite subscale on the ASI), possibly reflecting measurement issues. SS attendance was excellent. PTSD onset occurred prior to PG onset for most of the sample, and most believed the two disorders were related. Overall, we found that SS can be effectively conducted for comorbid PTSD and PG, with improvements in numerous domains and high acceptability. Limitations are discussed.