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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]

Chronic pain is highly prevalent among patients with opioid use disorder (OUD). However, little is known about how pharmacological treatments for OUD, for example, extended-release naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX), affect pain. To begin addressing this question, we performed a secondary analysis of pain data on a large prospective 24-week, open-label, randomized-controlled comparative effectiveness trial of XR-NTX versus BUP-NX (X:BOT trial). Participants' pain status was measured by the EuroQol (EQ-5D). Based on their responses to the pain question at baseline, participants were dichotomized into "Pain" versus "No Pain" categories. Participant's pain status was evaluated every 4 weeks. A mixed effects longitudinal logistic regression model was fitted to examine the differential effect of XR-NTX versus BUP-NX on pain, modelling pain at all available follow-up assessments, adjusted for age, sex, and baseline pain. A total of 474 individuals who were successfully inducted onto their assigned medications were included in this analysis. Among participants endorsing pain at baseline, substantial reductions in pain were observed over the course of the study in both treatment groups. Howecver reduction in pain was slightly greater in the group treated with XR-NTX than the one treated with BUP-NX (OR = 1.60 [95% CI: 1.07-2.40], P = 0.023). Future research using instruments and design specifically focused on pain could extend the present observations and evaluate their clinical significance. [ABSTRACT FROM AUTHOR]

Background and Objectives: To inform clinical practice, we identified subgroups of adults based on levels of depression symptomatology over time during opioid use disorder (OUD) treatment. Methods: Participants were 474 adults in a 24‐week treatment trial for OUD. Depression symptoms were measured using the 17‐item Hamilton Depression Rating Scale (HAM‐D) at nine‐time points. This was a secondary analysis of the Clinical Trials Network Extended‐Release Naltrexone versus Buprenorphine for Opioid Treatment (XBOT) trial using a growth mixture model. Results: Three distinct depression trajectories were identified: Class 1 High Recurring—10% with high HAM‐D with initial partial reductions (of HAM‐D across time), Class 2 Persistently High—5% with persistently high HAM‐D, and Class 3 Low Declining—85% of the participants, with low HAM‐D with early sustained reductions. The majority (low declining) had levels of depression that improved in the first 4 weeks and then stabilized across the treatment period. In contrast, 15% (high recurring and persistently high) had high initial levels that were more variable across time. The persistently high class had higher rates of opioid relapse. Discussion and Conclusions: In this OUD sample, most depressive symptomatology was mild and improved after medication treatment for opioid use disorder (MOUD). Smaller subgroups had higher depressive symptoms that persisted or recurred after the initiation of MOUD. Depressive symptoms should be followed in patients initiating treatment for OUD, and when persistent, should prompt further evaluation and consideration of antidepressant treatment. Scientific Significance: This study is the first to identify three distinct depression trajectories among a large clinical sample of individuals in MOUD treatment. [ABSTRACT FROM AUTHOR]

Introduction: Olfactory dysfunction is a common symptom of COVID-19. However, subjective perception of olfactory function does not always correlate well with more objective measures. This study seeks to clarify associations between subjective and psychophysical measures of olfaction and gustation in patients with subjective chemosensory dysfunction following COVID-19. Methods: Adults with persistent COVID-19-associated chemosensory disturbance were recruited for a prospective, longitudinal cohort study at a tertiary care institution. Participants provided subjective measures of olfactory and gustatory function and underwent psychophysical assessment using Sniffin’ Sticks olfactory and Monell gustatory tests. Results: Data analysis (n = 65) showed a statistically significant association between subjective and psychophysical measures of olfaction (p < 0.001). For each one-point increase in subjectively-reported olfactory ability, there is, on average, a 0.11 (95% CI: 0.06, 0.16; p < 0.001) point increase in TDI score while adjusting for age at baseline assessment, sex, and follow-up time. For each one-point increase in subjectively-reported olfactory ability, there is, on average, a 0.04 (95% CI: 0.02, 0.06; p < 0.001) point and 0.05 (95% CI: 0.03, 0.07; p < 0.001) point increase in discrimination and identification scores, respectively, when adjusting for age at baseline assessment, sex, and follow-up time. Conclusion: Subjective olfaction shows a mild to moderate association with psychophysical measures, but it fails to comprehensively assess persistent COVID-19-associated chemosensory deficits. The lack of significant association between subjective olfaction and threshold limits the utility of subjective olfaction in tracking recovery. These findings support the push for more widespread psychophysical chemosensory testing. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Rising rates of suicidal thoughts and behaviors (STBs) among U.S. Latina adolescents urgently need attention. Life is Precious (LIP) is a culturally responsive, community‐based, afterschool‐model program offering wellness‐support services to supplement outpatient mental health treatment for Latina adolescents experiencing STB's. This 12‐month quasi‐experimental pilot study explored LIP's impact on clinical outcomes.Latina adolescents newly enrolled in LIP and receiving outpatient treatment (n = 31) and those newly starting outpatient treatment only (n = 12; Usual Care) were assessed for Suicidal Ideation (Suicidal Ideation Questionnaire; SIQ) and depressive symptoms (Patient Health Questionnaire‐9). We estimated differences in mean scores using longitudinal linear mixed models and adjusted risk ratios (ARRs) of SIQ‐25%, SIQ‐50%, and PHQ‐9‐5‐point improvements using exact logistic models.The direction of the estimated impact of LIP was positive [differences (95% CIs): −15.5 (−34.16, 3.15) for SIQ; −1.16 (−4.39, 2.07) for PHQ‐9], with small‐to‐moderate nonsignificant effect sizes (0.19–0.34). LIP participants saw two to three times higher prevalence than controls of SIQ‐25%, SIQ‐50%, and PHQ‐9‐5‐point improvements; ARRs (95% CIs) were 1.91 (0.61, 3.45), 3.04 (0.43, 11.33), and 1.97 (0.44, 5.07), respectively. Suicidal behaviors also decreased in LIP.The effects of LIP were in positive directions across clinical outcomes, warranting further research on its effectiveness in decreasing STBs. [ABSTRACT FROM AUTHOR]

Background and Objectives: Limited research has explored sex differences in opioid use disorder medication (MOUD) treatment outcomes. The purpose of this study was to examine MOUD initiation onto buprenorphine‐naloxone (BUP‐NX) versus extended‐release naltrexone (XR‐NTX) by sex, and sex differences in clinical and psychosocial outcomes. Methods: Using data from a 24‐week open‐label comparative effectiveness trial of BUP‐NX or XR‐NTX, this study examined MOUD initiation (i.e., receiving a minimum one XR‐NTX injection or first BUP‐NX dose) and 24‐week self‐report outcomes. We used regression models to estimate the probability of MOUD initiation failure among the intent‐to‐treat sample (N = 570), and the main and interaction effects of sex on outcomes of interest among the subsample of participants who successfully initiated MOUD (n = 474). Results: In the intent‐to‐treat sample, the odds of treatment initiation failure were not significantly different by sex. In the subsample of successful MOUD initiates, the effect of treatment on employment at week 24 was significantly moderated by sex (p =.003); odds of employment were not significantly different among males by MOUD type; females randomized to XR‐NTX versus BUP‐NX had 4.63 times greater odds of employment (p <.001). Males had significantly lower odds of past 30‐day exchanging sex for drugs versus females (adjusted odds ratios [aOR] = 0.10, p =.004), controlling for treatment and baseline outcomes. Discussion and Conclusions: Further research should explore how to integrate employment support into OUD treatment to improve patient outcomes, particularly among women. Scientific Significance: The current study addressed gaps in the literature by examining sex differences in MOUD initiation and diverse treatment outcomes in a large, national sample. [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]

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]

Background and Objectives: Better understanding of predictors of opioid abstinence among patients with opioid use disorder (OUD) may help to inform interventions and personalize treatment plans. This analysis examined patient characteristics associated with opioid abstinence in the X:BOT (Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment) trial. Methods: This post-hoc analysis examined factors associated with past-month opioid abstinence at the 36-week follow-up visit among participants in the X:BOT study. 428 participants (75% of original sample) attended the visit at 36 weeks. Logistic regression models were used to estimate the probability of opioid abstinence across various baseline sociodemographics, clinical characteristics, and treatment variables. Results: Of the 428 participants, 143 (33%) reported abstinence from non-prescribed opioids at the 36-week follow-up. Participants were more likely to be opioid abstinent if randomized to XR-NTX (compared to BUP-NX), were on XR-NTX at week 36 (compared to those off OUD pharmacotherapy), successfully inducted onto either study medication, had longer time on study medication, reported a greater number of abstinent weeks, or had longer time to relapse during the 24-week treatment trial. Participants were less likely to be abstinent if Hispanic, had a severe baseline Hamilton Depression Rating (HAM-D) score, or had baseline sedative use. Conclusions: A substantial proportion of participants was available at follow-up (75%), was on OUD pharmacotherapy (53%), and reported past-month opioid abstinence (33%) at 36 weeks. A minority of patients off medication for OUD reported abstinence and additional research is needed exploring patient characteristics that may be associated with successful 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 comparative effectiveness of extended‐release naltrexone versus buprenorphine‐naloxone for opioid relapse prevention (X:BOT) trial showed that following induction, treatment with the sublingual agonist (buprenorphine‐naloxone, BUP‐NX) or injected antagonist (extended release naltrexone, XR‐NTX) produced similar reductions in opioid relapse in injection users with opioid use disorder (OUD). Because XR‐NTX reduces drinking in alcohol use disorder (AUD), we conducted a secondary analysis of the X:BOT sample of patients successfully inducted onto treatment to determine whether XR‐NTX (n = 204) was superior to BUP‐NX (n = 270) in reducing drinking or heavy drinking in patients with OUD. Methods: Standard drink units consumed were measured using the Timeline Follow‐back method. Mixed‐models regression was used to examine the monthly frequency of any drinking and heavy drinking over 6 months of treatment. We used a proportional hazard survival analysis to examine the time to first drink. Results: Both treatment groups reduced drinking from baseline to posttreatment (small to medium effect), but no differences between groups were detected. However, only 29% (n = 136) of the sample had AUD and 19% (n = 26/136) of those were abstinent before treatment. Analysis of a subsample enriched for possible drinking included 136 individuals with an AUD diagnosis plus 43 who did not have AUD, but reported at least one day of heavy drinking prior to the study. However, this subsample reported only 32% of days of any drinking with a median of only 13% of days designated as "heavy." Within this subsample, at baseline, the BUP‐NX group reported more mean drinks per drinking day than the XR‐NTX group (p = 0.03); however, there were no other significant group differences on drinking observed before, during, or at the end of treatment. Conclusions: There was an overall reduction in drinking during treatment of OUD using both agonist and antagonist medications, so that the hypothesis that XR‐NTX would be superior to BUP‐NX was not supported. The study is limited by low levels of comorbid AUD or heavy drinking observed in X:BOT trial participants seeking treatment for OUD. [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]

This study was designed to increase our understanding about characteristics and the impact of sensory symptoms (SS) and signs of hyperarousal (HA) in individuals with fragile X syndrome (FXS) from childhood through early adulthood and by gender. Data derived from the Fragile X Online Registry With Accessible Research Database (FORWARD), a natural history study of FXS, were analyzed using descriptive statistics and multivariate linear and logistic regression models to examine SS and signs of HA, their impact on behavioral regulation and limitations on the subject/family. The sample (N = 933) consisted of 720 males and 213 females. More males were affected with SS (87% vs. 68%) and signs of HA (92% vs. 79%). Subjects who were endorsed as having a strong sensory response had more comorbidities, including behavioral problems. The predominant SS was difficulty with eye gaze that increased with age in both genders. As individuals age, there was less use of non-medication therapies, such as occupational therapy (OT)/physical therapy (PT), but there was more use of psychopharmacological medications and investigational drugs for behaviors. Multiple regression models suggested that endorsing SS and signs of HA was associated with statistically significantly increased ABC-C-I subscale scores and limited participation in everyday activities. This study improves our understanding of SS and signs of HA as well as their impact in FXS. It supports the need for more research regarding these clinical symptoms, especially to understand how they contribute to well-known behavioral concerns. [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]