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Ecological Momentary Assessment (EMA) holds promise for providing insights into daily life experiences when studying mental health phenomena. However, commonly used mixed-effects linear statistical models do not fully utilize the richness of the ultidimensional time-varying data that EMA yields. Recurrent Neural Networks (RNNs) provide an alternative data analytic method to leverage more information and potentially improve prediction, particularly for non-normally distributed outcomes. As part of a broader research study of suicidal thoughts and behavior in people with borderline personality disorder (BPD), eighty-four participants engaged in EMA data collection over one week, answering questions multiple times each day about suicidal ideation (SI), stressful events, coping strategy use, and affect. RNNs and mixed-effects linear regression models (MEMs) were trained and used to predict SI. Root mean squared error (RMSE), mean absolute percent error (MAPE), and a pseudo-R2 accuracy metric were used to compare SI prediction accuracy between the two modeling methods. RNNs had superior accuracy metrics (full model: RMSE = 3.41, MAPE = 42 %, pseudo-R2 = 26 %) compared with MEMs (full model: RMSE = 3.84, MAPE = 56 %, pseudo-R2 = 16 %). Importantly, RNNs showed significantly more accurate prediction at higher values of SI. Additionally, RNNs predicted, with significantly higher accuracy, the SI scores of participants with depression diagnoses and of participants with higher depression scores at baseline. In this EMA study with a moderately sized sample, RNNs were better able to learn and predict daily SI compared with mixed-effects models. RNNs should be considered as an option for EMA analysis. • Recurrent Neural Networks had superior predictive ability for Suicidal Ideation compared to Mixed-Effects Models • Both methods were less accurate in the higher range of Suicidal Ideation values • Recurrent Neural Networks performed better for high values than Mixed-Effects Models, and for those with depression symptoms • Proposed extensions of Recurrent Neural Network modeling further improved prediction accuracy in the high ideation range [ABSTRACT FROM AUTHOR]

Background and Objectives: Research has examined reductions in patient distress recounting trauma narratives in Prolonged Exposure (PE) for posttraumatic stress disorder (PTSD). It remains unclear whether changes in distress and avoidance related to environmental trauma reminders matter in PE and other PTSD treatments, including non-exposure Interpersonal Psychotherapy (IPT).Methods: Data came from adults with chronic PTSD (N = 92) who completed a treatment trial comparing PE, IPT, and Relaxation Therapy (RT). We employed the Self-Initiated In-Vivo Exposure Scale (SIIVES), which measures patient distress from and avoidance of situational trauma reminders, to calculate reliable change in distress and avoidance. PTSD symptoms, depression, quality of life, and functioning assessments were collected before and after 14 weeks of treatment.Results: Overall, 48.1% of patients experienced reliable change in avoidance, while 51.9% showed reliable change in distress. Rates of reliable change did not differ by treatment group, although PE appeared to achieve reliable change earlier. Only one baseline characteristic predicted reliable change: patients with comorbid depression were less likely to reliably change in avoidance. At post-treatment, patients achieving reliable change had lower PTSD severity and depression and increased quality of life and social functioning. Statistical modeling revealed that changes in distress and avoidance related to subsequent reduction in PTSD symptoms in all three treatment groups, though this relationship appeared strongest in PE.Limitations: The sample was relatively small.Conclusions: Change in avoidance and distress associated with situational trauma reminders was associated with a range of clinical outcomes and may represent important factors in multiple PTSD psychotherapies. [ABSTRACT FROM AUTHOR]

Background: Extended-release naltrexone (XR-NTX) is an effective maintenance treatment for opioid use disorder, but induction from active opioid use is a challenge as individuals must complete detoxification before induction. We aimed to determine whether use of methadone or buprenorphine, long acting agonist opioids commonly used for detoxification, were associated with decreased likelihood of induction onto XR-NTX.Methods: We performed a secondary analysis of a large open-label randomized trial of buprenorphine versus XR-NTX for treatment of individuals with opioid use disorder recruited from eight short term residential (detoxification) units. This analysis only included individuals randomized to the XR-NTX arm of the trial (N = 283). The method of detoxification varied according to usual practices at each inpatient program. Logistic regression models estimating the log-odds of induction onto XR-NTX were fit, with detoxification regimen received as the predictor.Results: In the unadjusted logistic regression model, detoxification drug received (either methadone or buprenorphine) was significantly associated with decreased likelihood of induction onto XR-NTX compared to receiving non-opioid detoxification (Overall: P < 0.001); buprenorphine vs non-opioid detoxification: OR (95% CI) = 0.32 (0.15-0.67); methadone vs non-opioid detoxification: OR (95% CI) = 0.23 (0.11-0.46). After controlling for site as a random effect, the association of detoxification drug with induction success lost statistical significance.Conclusions: Use of agonist medication during detoxification was associated with XR-NTX induction failure. Medication choice was determined by each site's clinical practice and therefore this association could not be separated from other site level variables.Clinical Trial Registration: NCT02032433. [ABSTRACT FROM AUTHOR]

Ketamine shows promise as a rapidly-acting treatment for depression and suicidal ideation, but side effects and abuse potential limit its use. Understanding its mechanism of action could help develop analogous but safer drugs. This post hoc study explored relationships of ketamine and metabolites, including hydroxynorketamine enantiomers, (2S,6S)- and (2R,6R)- HNK, to clinical response in a subgroup from a published trial in suicidal depression. Depressed adults with clinically significant suicidal ideation were randomized to double-blind infusion of sub-anesthetic ketamine or midazolam. Ketamine and metabolites were measured after infusion (N = 53). Plasma (2R,6R) -HNK was associated with change (higher levels correlated with less clinical improvement) from baseline to 24 h post-infusion of depression (HDRS-24: Spearman r = 0.37, p = 0.009) and suicidal thoughts (SSI: Spearman r = 0.29, p = 0.041). There were similar correlations with weekly follow-up clinical rating scores for both HNK enantiomers and dehydronorketamine (DHNK). Ketamine and norketamine were not associated with change in depression or suicidal ideation (unadjusted p > 0.28). [ABSTRACT FROM AUTHOR]

Patients with schizophrenia show reduced NMDA glutamate receptor–dependent auditory plasticity, which is rate limiting for auditory cognitive remediation (AudRem). We evaluate the utility of behavioral and neurophysiological pharmacodynamic target engagement biomarkers, using a d -serine+AudRem combination. Forty-five participants with schizophrenia or schizoaffective disorder were randomized to 3 once-weekly AudRem visits + double-blind d -serine (80, 100, or 120 mg/kg) or placebo in 3 dose cohorts of 12 d -serine and 3 placebo-treated participants each. In AudRem, participants indicated which paired tone was higher in pitch. The primary outcome was plasticity improvement, operationalized as change in pitch threshold between AudRem tones [(test tone Hz − reference tone Hz)/reference tone Hz] between the initial plateau pitch threshold (mean of trials 20–30 of treatment visit 1) to pitch threshold at the end of visit(s). Target engagement was assessed by electroencephalography outcomes, including mismatch negativity (pitch primary). There was a significant overall treatment effect for plasticity improvement (p =.014). Plasticity improvement was largest within the 80 and 100 mg/kg groups (p <.001, d > 0.67), while 120 mg/kg and placebo-treated participants showed nonsignificant within-group changes. Plasticity improvement was seen after a single treatment and was sustained on subsequent treatments. Target engagement was demonstrated by significantly larger mismatch negativity (p =.049, d = 1.0) for the 100 mg/kg dose versus placebo. Our results demonstrate sufficient proof of principle for continued development of both the d -serine+AudRem combination and our target engagement methodology. The ultimate utility is dependent on the results of an ongoing larger, longer study of the combination for clinically relevant outcomes. [ABSTRACT FROM AUTHOR]

We examined relationships between the serotonin system and stress in major depression and suicidal behavior. Twenty-five medication-free depressed participants (13 suicide attempters) underwent same-day [11C]DASB and [11C]CUMI-101 positron emission tomography (PET) imaging. Binding potential (BP ND) to the serotonin transporter (5-HTT) and serotonin 1A (5-HT 1A) receptor, respectively, was quantified using the NRU 5-HT atlas, reflecting distinct spatial distributions of multiple serotonin targets. Ecological momentary assessment (EMA) measured current stress over one week proximal to imaging. EMA stress did not differ between attempters and non-attempters. In all depressed participants, 5-HTT and 5-HT 1A BP ND were unrelated to EMA stress. There were region-specific effects of 5-HTT (p=0.002) and 5-HT 1A BP ND (p=0.03) in attempters vs. nonattempters. In attempters, region-specific associations between 5-HTT (p=0.03) and 5-HT 1A (p=0.005) BP ND and EMA stress emerged. While no post-hoc 5-HTT BP ND correlations were significant, 5-HT 1A BP ND correlated positively with EMA stress in attempters in 9/10 regions (p-values<0.007), including the entire cortex except the largely occipital region 5. Brodmann-based regional analyses found diminished effects for 5-HTT and subcortically localized positive corrrelations between 5-HT 1A and EMA stress, in attempters only. Given comparable depression severity and childhood and current stress between attempters and nonattempters, lower 5-HTT binding in attempters vs. nonattempters may suggest a biological risk marker. Localized lower 5-HTT and widespread higher 5-HT 1A binding with stress among attempters specifically may suggest that a serotonergic phenotype might be a key determinant of risk or resiliency for suicidal behavior. [ABSTRACT FROM AUTHOR]

Background Attention bias to threat (selective attention toward threatening stimuli) has been frequently found in anxiety disorder samples, but its distribution both within and beyond this category is unclear. Attention bias has been studied extensively in social anxiety disorder (SAD) but relatively little in obsessive compulsive disorder (OCD), historically considered an anxiety disorder, or anorexia nervosa (AN), which is often characterized by interpersonal as well as body image/eating fears. Methods Medication-free adults with SAD (n = 43), OCD (n = 50), or AN (n = 30), and healthy control volunteers (HC, n = 74) were evaluated for attention bias with an established dot probe task presenting images of angry and neutral faces. Additional outcomes included attention bias variability (ABV), which summarizes fluctuation in attention between vigilance and avoidance, and has been reported to have superior reliability. We hypothesized that attention bias would be elevated in SAD and associated with SAD severity. Results Attention bias in each disorder did not differ from HC, but within the SAD group attention bias correlated significantly with severity of social avoidance. ABV was significantly lower in OCD versus HC, and it correlated positively with severity of OCD symptoms within the OCD group. Conclusions Findings do not support differences from HC in attention bias to threat faces for SAD, OCD, or AN. Within the SAD sample, the association of attention bias with severity of social avoidance is consistent with evidence that attention bias moderates development of social withdrawal. The association of ABV with OCD diagnosis and severity is novel and deserves further study. [ABSTRACT FROM AUTHOR]

Objective: Polysubstance use may complicate treatment outcomes for individuals who use opioids. This research aimed to examine the prevalence of polysubstance use in an opioid use disorder treatment trial population and polysubstance use's association with opioid relapse and craving.Methods: This study is a secondary data analysis of individuals with opioid use disorder who received at least one dose of medication (n = 474) as part of a 24-week, multi-site, open label, randomized Clinical Trials Network study (CTN0051, X:BOT) comparing the effectiveness of extended-release naltrexone versus buprenorphine. Models examined pretreatment polysubstance use and polysubstance use during the initial 4 weeks of treatment on outcomes of relapse by week 24 of the treatment trial and opioid craving.Results: Polysubstance use was generally not associated with treatment outcomes of opioid relapse and craving. Proportion of days of pretreatment sedative use was associated with increased likelihood of opioid relapse (OR: 1.01, 95 % CI: 1.00-1.02). Proportion of days of cocaine use during the initial 4 weeks of treatment was associated with increased likelihood of opioid relapse (OR: 1.05, 95 % CI: 1.01-1.09) but this effect was no longer significant once the potential of confounding by opioid use was considered. Sedative use during initial 4 weeks of treatment was associated with increased opioid craving (b: 0.77, 95 % CI: 0.01-1.52). The study found no other significant relationships.Conclusions: In the current study population, polysubstance use was only marginally associated with 24-week treatment outcomes. [ABSTRACT FROM AUTHOR]

Aim: This report examined naturalistic opioid use outcomes and utilization of medications for opioid use disorder (MOUD) 36 weeks post-randomization in the National Drug Abuse Treatment Clinical Trials Network (CTN) Extended-Release Naltrexone (XR-NTX) versus Buprenorphine-Naloxone (BUP-NX) for Opioid Treatment trial (CTN-0051, X:BOT).Design: X:BOT was a multisite, randomized, 24-week comparative effectiveness trial of BUP-NX (N = 287) and XR-NTX (N = 283). Study medications were discontinued following treatment completion, relapse, or dropout. Participants were encouraged to continue MOUD. This report examined opioid use outcomes in 428 (75%) of the 570 participants who attended the 36-week follow-up visit.Setting and Participants: Adults with opioid use disorder recruited from 8 community treatment programs across the United States.Measurements: Outcomes included medication status (on/off MOUD), type of MOUD (BUP-NX, XR-NTX, or methadone), abstinence from non-prescribed opioids, opioid use days, relapse, and other substance use 30 days prior to the 36-week visit. Relapse was defined as opioid use for 4 consecutive weeks or 7 consecutive days in the past month. Baseline and clinical variables included opioid use severity, intravenous drug use, study medication assignment, and induction status.Findings: Of the 428 participants who completed the 36-week visit, 225 (53%) of participants were receiving MOUD and 203 (47%) were not. Compared to those off medication, participants on medication had fewer opioid use days (4.4 days (SD 9.0) versus 9.8 days (SD 12.1)), fewer met relapse criteria (37 (16.4%) versus 79 (38.9%)), and reported less stimulant use (34 (15.2%) versus 56 (27.7%)) and sedative use (14 (6.3%) versus 31 (15.3%)). There was no difference in abstinence rates between those on or off MOUD. A greater proportion of participants on XR-NTX (47 (53.4%) of 88 participants) were abstinent from non-prescribed opioids compared to those on buprenorphine (28 (23.3%) of 120 participants).Conclusions: Naturalistic outcomes data showed that despite potential barriers to continuing treatment in the community, about half of individuals were on opioid use disorder pharmacotherapy at follow-up and those on medication generally had better outcomes. Future research should explore barriers and facilitators to treatment retention in community settings; and developing interventions tailored to improve treatment engagement and adherence. [ABSTRACT FROM AUTHOR]

Background: The distinct pharmacological properties and clinical uses of extended-release naltrexone (XR-NTX) and sublingual buprenorphine-naloxone (BUP-NX) present challenges in analyzing patient outcomes.Methods: We conducted a secondary analysis of a multi-site randomized trial comparing XR-NTX with sublingual BUP-NX treatment for opioid use disorder initiated during inpatient detoxification and continued in outpatient treatment. Urine testing data for non-study opioids from the last 22 weeks of the 24-week trial were analyzed in both a per-protocol sample (n = 474 participants who received at least one dose of medication) and a completers sample (n = 211 participants who received all XR-NTX doses or all BUP-NX prescriptions). The present analyses sought to identify differences in the weekly percentages of opioid-positive urine tests between participants treated with the two medications.Results: The proportion of opioid-positive tests in both conditions was less than 20 % for 21 of the 22 weeks in the per-protocol sample and all 22 weeks in the completers sample. Generalized linear mixed model analyses revealed a significant treatment (XR-NTX vs. BUP-NX) X week (weeks 3-24) interaction in the per-protocol sample but not the completers sample. In the per-protocol analysis, the BUP-NX, compared to XR-NTX, had significantly greater proportions of opioid-positive tests in 14 out of the 22 weeks.Conclusions: Longitudinal modeling approaches that utilize flexible procedures for handling missing data can offer a different perspective on study findings. Results from the present analyses suggest that XR-NTX appeared to be somewhat more effective than BUP-NX in reducing illicit opioid use in the per-protocol sample. [ABSTRACT FROM AUTHOR]

Indigenous people experience health disparities, including higher rates of substance use disorders (SUDs). Digital therapeutics are a growing platform for treatment services and have the potential to expand access to culturally responsive interventions for Indigenous people. As one of the first randomized controlled trials for SUDs for American Indian and Alaska Native (AI/AN) adults, the aim of this study was to pilot test the efficacy of a culturally tailored intervention among urban Indigenous adults. The study used a randomized controlled parallel design of 12 weeks of treatment-as-usual (TAU) (n = 26) versus TAU + Therapeutic Education System-Native Version (TES-NAV) (n = 27) with follow-up assessments at end of treatment and week 24 in an urban outpatient addiction treatment program for Native American adults. TAU consisted of individual/group counseling and cultural activities. The TES-NAV arm comprised TAU + 26 self-directed culturally tailored digital skills-based modules grounded in the community reinforcement approach with contingency management for abstinence and module completion. Primary outcome was longest consecutive weeks of abstinence from drugs and heavy drinking measured using self-report (Timeline Followback) and urine alcohol and drug toxicology screen during 12 weeks of treatment. Secondary outcomes were percent days abstinence during and posttreatment, coping strategies, social connectedness, and substance use and sexual risk behaviors. The study enrolled fifty-three (52.8 % male) AI/AN adults seeking treatment for a SUD. Although the study did not detect a benefit of TAU+TES-NAV over TAU on the primary outcome (Median = 2 consecutive weeks of abstinence for both arms) at end of treatment (treatment effect: Z = −0.78, p = 0.437), TAU+TES-NAV participants did demonstrate significantly greater percent days of abstinence at the week 24 follow-up (69.3 % versus 49.0 % for TAU; t = 2.08, p = 0.045) and significantly greater change in social connectedness mean score, baseline to week 12 (Z = −2.66, p = 0.011), compared to TAU. The study detected no differences between treatment arms for coping strategies or risk behaviors. The addition of TES-NAV to TAU did not significantly improve consecutive weeks of abstinence from drugs or heavy drinking; however, several secondary findings suggest promise for a culturally tailored digital therapeutic SUD intervention among urban Indigenous people. #NCT03363256. • Indigenous people face substance use disorder disparities. • Adapted digital interventions may improve access to culturally responsive treatment. • A digital intervention did not significantly improve in-treatment abstinence. • A digital intervention improved post treatment abstinence and social connection. [ABSTRACT FROM AUTHOR]

While suicide-specific psychosocial interventions often teach coping skills to suicidal individuals, little is known about the strategies that individuals intuitively use on their own to cope with suicidal ideation in everyday life. The present study used Ecological Momentary Assessment (EMA) to examine the effectiveness of specific coping strategies individuals use naturally to reduce the intensity of suicidal thinking. Fifty participants endorsing suicidal ideation with co-morbid mood disorder and borderline personality disorder completed one week of EMA. Real-time use, perceived effectiveness of 7 common coping strategies and intensity of suicidal ideation were assessed at 6 epochs (i.e., timepoints) each day. Participants reported using an average of 4 coping strategies per epoch. Factor analysis (FA) (exploratory followed by confirmatory FA) identified two coping factors: one that included distraction/positive activity-based strategies (i.e., keeping busy, socializing, positive thinking, and doing something good for self) and a second that contained mindfulness-oriented strategies (i.e., finding perspective, calming self, and sitting with feelings until they pass). Although participants perceived all coping strategies as effective, only strategies in the first factor, distraction/positive activity-oriented strategies, lowered the intensity of suicidal thoughts in everyday life. Furthermore, baseline suicidal ideation was inversely related to overall use of coping strategies and particularly use of coping strategies that were found to lead to lowered suicidal ideation. Distraction/positive activity based strategies are helpful in decreasing suicidal ideation in the short-term. These findings can help clinicians advise patients about strategies to use to cope with suicidal thoughts to prevent acting on them in a crisis and they also have the potential to inform development of psychosocial interventions to prevent suicide. [ABSTRACT FROM AUTHOR]

Background: To assess within and across diagnosis variability we examined fear processing in healthy controls (HC) and three diagnostic groups that share symptoms of pathological anxiety: obsessive compulsive disorder (OCD); social anxiety disorder (SAD), and anorexia nervosa (AN).Methods: Unmedicated adults (N=166) participated in a paradigm assessing associative fear acquisition, extinction, extinction recall, and fear renewal. Data were analyzed from two perspectives: comparison of each disorder to HC and exploratory latent class analysis (LCA) of the combined data.Results: The diagnosis-based analyses indicated significantly increased fear renewal in OCD and trends toward decreased extinction recall in OCD and increased renewal in SAD. The LCA indicated four Response Types, none of which were congruent with the diagnostic categories. Most participants had a normative response (50%) or a moderate extinction recall deficit (30%). The two remaining groups (8% each) had more extreme responses: one showed complete failure of extinction recall; the other persistent arousal in expectation of, but prior to, actual conditioning (threat sensitivity).Limitations: Due to small sample size (N=20) results for AN are regarded as preliminary.Conclusions: Our diagnosis-based findings are consistent with previous data suggesting an association between pathological anxiety and difficulties maintaining fear extinction. The LCA reveal substantial within-diagnosis heterogeneity in fear processing and support inclusion of empirically driven approaches as a complement to standard analyses. This heterogeneity may also have implications for treatment, particularly cognitive behavioral therapy, which relies on strengthening extinction recall and requires patients to tolerate anxious expectation in order to engage with feared situations. [ABSTRACT FROM AUTHOR]

Introduction: The current study aims to characterize weight-change trajectories and their concomitant associations with prospectively measured dieting and other disordered eating behaviors among initially nonoverweight adolescents during the transition to adulthood.Methods: A population-based sample (n=1,091) self-reported their height/weight, dieting, unhealthy weight-control behaviors, and binge eating at 5-year intervals between 1998/1999 and 2013/2014, spanning early/middle adolescence through middle/late young adulthood. Data were analyzed in 2016/2017.Results: Groups were categorized as those who were never overweight (n=562), were overweight during at least one measurement point and gained weight more rapidly (n=246) or gradually (n=238) than their peers, or were overweight during at least one measurement point but returned to nonoverweight status by middle/late young adulthood (n=45). Thus, nearly half of adolescents became overweight during the transition to adulthood. Those who were never overweight had the lowest rates of dieting (males: F[9, 1,314]=2.54, p=0.0069, females: F[9, 1,927]=3.02, p=0.0014) and unhealthy weight-control behaviors (males: F[9, 1,313]=3.30, p=0.0005, females: F[9, 1,927]=3.02, p=0.0014), whereas some of these behaviors tended to track with weight gain in rapid and gradual weight gainers.Conclusions: Although adolescents who are already overweight are most frequently targeted for weight-gain prevention and early intervention programs, results suggest that healthy lifestyle interventions could also benefit individuals who may be perceived as low risk for overweight in adulthood by nature of being nonoverweight in adolescence. Dieting and unhealthy weight-control behaviors tended to be associated with weight gain, suggesting that they are ineffective in addition to being potentially harmful. [ABSTRACT FROM AUTHOR]

Background: Methamphetamine use is increasing among persons with opioid use disorder (OUD). The study aims were to describe methamphetamine/amphetamine (MA/A) use among patients treated for OUD with buprenorphine/naloxone (BUP-NX) or extended-release naltrexone (XR-NTX), and to explore associations between treatment arm and MA/A use.Methods: Secondary analysis of data from a multi-site, open-label, randomized controlled trial of XR-NTX versus BUP-NX for 24 weeks. The outcome variable was MA/A use defined by either positive urine drug toxicology or self-report. The main predictor was treatment assignment (BUP-NX v. XR-NTX). Longitudinal mixed-effects logistic regression models were fit to model the odds of MA/A use during the study. Additional predictors included study visit and baseline MA/A use.Results: Among the sample of 570 participants with OUD, baseline use of MA/A was observed in 105 (18.4%). There was no significant treatment effect over the study period, though BUP-NX subjects, on average, had about half the odds of MA/A use compared to XR-NTX subjects (OR=0.50; p = 0.051). In the same model, baseline MA/A use and study visit were both significantly associated with MA/A use over time.Conclusion: In this sample of treated OUD patients, nearly a fifth of participants had MA/A use at baseline and the frequency of use did not decline over time: in fact, the odds of use slightly increased for each later visit. These secondary analyses found no significant difference in MA/A use between BUP-NX and XR-NTX treatment arms, however, the observation of less MA/A in the buprenorphine arm merits further investigation.Clinical Trial Registration: ClinicalTrials.gov (NCT02032433). [ABSTRACT FROM AUTHOR]