Text And Telephone Screening And Referral Improved Detection And Treatment Of Maternal Mental Health Conditions.

Effective screening and referral practices for perinatal mental health disorders, perinatal substance use disorders (SUDs), and intimate partner violence are greatly needed to reduce maternal morbidity and mortality. We conducted a randomized controlled trial from January 2021 to April 2023 comparing outcomes between Listening to Women and Pregnant and Postpartum People (LTWP), a text- and telephone-based screening and referral program, and usual care in-person screening and referral within the perinatal care setting. Participants assigned to LTWP were three times more likely to be screened compared with those assigned to usual care. Among participants completing a screen, those assigned to LTWP were 3.1 times more likely to screen positive, 4.4 times more likely to be referred to treatment, and 5.7 times more likely to attend treatment compared with those assigned to usual care. This study demonstrates that text- and telephone-based screening and referral systems may improve rates of screening, identification, and attendance to treatment for perinatal mental health disorders and perinatal SUDs compared with traditional in-person screening and referral systems. System-level changes and complementary policies and insurance payments to support adoption of effective text- and telephone-based screening and referral programs are needed.

Characterization of peer support services for substance use disorders in 11 US emergency departments in 2020: findings from a NIDA clinical trials network site selection process.

INTRODUCTION: Emergency departments (ED) are incorporating Peer Support Specialists (PSSs) to help with patient care for substance use disorders (SUDs). Despite rapid growth in this area, little is published regarding workflow, expectations of the peer role, and core components of the PSS intervention. This study describes these elements in a national sample of ED-based peer support intervention programs. METHODS: A survey was conducted to assess PSS site characteristics as part of site selection process for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) evaluating PSS effectiveness, Surveys were distributed to clinical sites affiliated with the 16 CTN nodes. Surveys were completed by a representative(s) of the site and collected data on the PSS role in the ED including details regarding funding and certification, services rendered, role in medications for opioid use disorder (MOUD) and naloxone distribution, and factors impacting implementation and maintenance of ED PSS programs. Quantitative data was summarized with descriptive statistics. Free-text fields were analyzed using qualitative content analysis. RESULTS: A total of 11 surveys were completed, collected from 9 different states. ED PSS funding was from grants (55%), hospital funds (46%), peer recovery organizations (27%) or other (18%). Funding was anticipated to continue for a mean of 16 months (range 12 to 36 months). The majority of programs provided "general recovery support (81%) Screening, Brief Intervention, and Referral to Treatment (SBIRT) services (55%), and assisted with naloxone distribution to ED patients (64%). A minority assisted with ED-initiated buprenorphine (EDIB) programs (27%). Most (91%) provided services to patients after they were discharged from the ED. Barriers to implementation included lack of outpatient referral sources, barriers to initiating MOUD, stigma at the clinician and system level, and lack of ongoing PSS availability due to short-term grant funding. CONCLUSIONS: The majority of ED-based PSSs were funded through time-limited grants, and short-term grant funding was identified as a barrier for ED PSS programs. There was consistency among sites in the involvement of PSSs in facilitation of transitions of SUD care, coordination of follow-up after ED discharge, and PSS involvement in naloxone distribution.

The lived experiences and treatment needs of women with opioid use disorder and posttraumatic stress symptoms: A mixed methods study.

INTRODUCTION: Women show a gender-specific risk for co-occurring opioid use disorder (OUD) and posttraumatic stress disorder (PTSD). Expert groups have called for the development of integrated treatments for women with OUD/PTSD, but there remains limited information on such interventions. METHODS: This mixed-methods study interviewed and surveyed 10 women with current or past OUD and co-occurring posttraumatic stress symptoms (PTSS) and 16 providers who work with these women. Interviews and surveys queried patient participants' and providers' experiences of OUD/PTSS and how to best design an integrated, trauma-focused treatment for OUD/PTSD. RESULTS: Patient participants (90 % white, 90 % mothers, Mage = 45.70) met criteria for severe, lifetime OUD and 40 % met a provisional diagnosis for PTSD. Four themes emerged for participants' experiences of OUD/PTSS: 1) numerous stressors; 2) shame; 3) multiple motivations to use opioids; and 4) a cycle of trauma and opioid use. Four themes emerged regarding patient participants' perceptions on the development of an OUD/PTSD treatment: 1) mixed attitudes towards medications for OUD; 2) barriers to treatment (e.g., insufficient treatments and contextual factors); 3) treatment facilitators (e.g., social support); and 4) preferences in treatment (e.g., trauma-focused, gender-focused, family content, ambivalence around group therapy). Providers (Mage = 38.94) were primarily white women (76.5 %). Two themes emerged from their experiences working with women with OUD/PTSS: 1) perceiving women to use opioids to regulate emotions and 2) gender differences in trauma types. Three themes emerged for providers' perceptions on the development of an OUD/PTSD treatment: 1) barriers to treatment (e.g., chaotic lives, contextual factors, family); 2) treatment facilitators (e.g., trust and external motivations); and 3) desired treatment modifications (e.g., stabilization, early skills in therapy, flexibility in therapy, social supports, safety guidelines, and assistance in identifying an index trauma). Most participants (90.0 %) and providers (93.5 %) preferred working on OUD/PTSD symptoms simultaneously rather than separately. CONCLUSIONS: Findings demonstrate the need to modify integrated treatments to meet the preferences of providers and women with OUD/PTSS and OUD/PTSD. Treatments should consider therapeutic content, structure, contextual factors, social support, and PTSD severity to enhance uptake and reach.

Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity: A Systematic Review.

Importance: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

Reduced executive and reward connectivity is associated with smoking cessation response to repetitive transcranial magnetic stimulation: A double-blind, randomized, sham-controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) can reduce cue-elicited craving, decrease cigarette consumption, and increase the abstinence rate in tobacco use disorders (TUDs). We used functional magnetic resonance imaging (fMRI) to investigate the effect of 10 sessions of rTMS on cortical activity and neural networks in treatment-seeking smokers. Smoking cue exposure fMRI scans were acquired before and after the 10 sessions of active or sham rTMS (10 Hz, 3000 pulses per session) to the left dorsal lateral prefrontal cortex (DLPFC) in 42 treatment-seeking smokers (≥ 10 cigarettes per day). Brain activity and functional connectivity were compared before and after 10 sessions of rTMS. Ten sessions of rTMS significantly reduced the number of cigarettes consumed per day (62.93%) compared to sham treatment (39.43%) at the end of treatment (p = 0.027). fMRI results showed that the rTMS treatment increased brain activity in the dorsal anterior cingulate cortex (dACC) and DLPFC, but decreased brain activity in the bilateral medial orbitofrontal cortex (mOFC). The lower strength of dACC and mOFC connectivity was associated with quitting smoking (Wald score = 5.00, p = 0.025). The reduction of cigarette consumption significantly correlated with the increased brain activation in the dACC (r = 0.76, p = 0.0001). By increasing the brain activity in the dACC and prefrontal cortex and decreasing brain activity in the mOFC, 10 sessions of rTMS significantly reduced cigarette consumption and increased quit rate. Reduced drive-reward and executive control functional connectivity was associated with the smoking cessation effect from rTMS. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02401672.

Trends in Self-Reported Fentanyl and Other Illicit Substance Use in South Carolina Emergency Department Patients, 2020-2022.

BACKGROUND: Opioid-involved deaths are continuing to increase across the United States, exceeding 100,000 for the first time in 2021. Contamination with, and intentional use of, synthetic opioids such as fentanyl are a major driver of this increase. Utilizing self-report substance use data of patients being treated in the emergency department (ED) can be useful to determine which substances patients are intentionally seeking. OBJECTIVES: 1) Examine changes in self-reported illicit substance use (including fentanyl) over time; 2) Examine changes in the co-occurrence of self-reported fentanyl with other illicit substance use over time. METHODS: All patients presenting to the study EDs that answered anything other than "never" on the National Institute on Drug Abuse Quick Screen and were seen by a peer recovery specialist in the ED between July 1, 2020 and December 31, 2022 were included for analysis. The substance of use as reported by each patient was recorded by the peer recovery specialist. Differences in substance use by type over time were examined using chi-squared tests of proportions. RESULTS: There were 7568 patients that met inclusion criteria. Self-reported fentanyl (1760%; p < 0.0001) and cocaine (82%; p = 0.034) use increased, whereas heroin use (16%; p < 0.0001) decreased. CONCLUSIONS: Self-reported fentanyl and cocaine use has increased significantly in South Carolina ED patients between 2020 and 2022. Given the high morbidity and mortality associated with fentanyl and fentanyl analog use, further measures to identify these patients and provide harm reduction and treatment from the ED setting are warranted.

Novel Collaborations Across Training Programs to Support Mentoring in Sex Differences Research.

There is a critical need to develop a capable and well-trained workforce dedicated to the systematic study of sex differences and examination of sex as a biological variable. Through the support of the Office of Research on Women's Health and partner National Institute of Health centers, the Specialized Centers of Research Excellence (SCORE) on Sex Differences Career Enhancement Cores (CECs) were established to help address this need. We describe the integration of the Medical University of South Carolina SCORE CEC with other National Institutes of Health (NIH)-funded and institutional training programs to promote training synergies, share resources, and enhance mentorship opportunities. Benefits of developing an intrainstitutional training platform have included facilitating cross-disciplinary interactions, encouragement of peer mentorship, and reduced burden on training program leadership.

Inpatient Low-dose Transitions From Full Agonist Opioids Including Methadone Onto Long-acting Depot Buprenorphine: Case Series From a Multicenter Clinical Trial.

OBJECTIVES: Persons with opioid use disorder (OUD) suffer disproportionately from morbidity and mortality related to serious addiction-related infections requiring hospitalization. Long-acting buprenorphine (LAB) is an underused medication for OUD that may facilitate linkage to care and treatment retention when administered before hospital discharge. Transition onto buprenorphine in the inpatient setting is often complicated by pain, active infection management, potential surgical interventions, and risk of opioid withdrawal in transition from full agonists to a partial agonist. METHODS: The COMMIT Trial is a randomized controlled trial evaluating LAB administered by infectious disease physicians and hospitalists compared with treatment as usual for persons with OUD hospitalized with infections. We report a case series of participants on full agonist opioids including methadone who were transitioned to sublingual buprenorphine using low-dose ( microdosing ) strategies followed by LAB injection. RESULTS: Seven participants with current opioid use disorder and life-threatening infections, all with significant concurrent pain and many requiring surgical intervention, underwent low-dose transitions starting at buccal buprenorphine doses ranging from 225 µg to 300 µg 3 times a day on the first day. All were well tolerated with average time to LAB injection of 7.5 days (range, 5-10 days). CONCLUSIONS: Inpatient low-dose buprenorphine transition from full agonist opioids including methadone onto LAB is feasible even in those with complex hospitalizations for concurrent infections and/or surgery. This strategy facilitates dosing of LAB before hospital discharge when risk of opioid relapse and overdose are significant.

Efficacy of mindfulness-based relapse prevention in a sample of veterans in a substance use disorder aftercare program: A randomized controlled trial.

BACKGROUND: Complementary integrative medicine, such as mindfulness-based interventions, (MBI) have demonstrated efficacy in the treatment of depression, anxiety, substance use disorders (SUDs), and pain. Mindfulness-based relapse prevention (MBRP) is an aftercare intervention targeting SUD relapse that integrates cognitive-behavioral relapse prevention and mindfulness meditation practices, raising awareness of substance use triggers and reactive behavioral patterns. This study evaluated the efficacy of MBRP in reducing relapse in veterans following completion of an SUD treatment program. METHODS: This study was a two-site, randomized controlled trial comparing MBRP to 12-step facilitation (TSF) aftercare in military veterans following completion of intensive treatment for SUDs. The 8 weeks of 90-minute, group-based MBRP or TSF sessions were followed by 3-, 6- and 10-month follow-up periods with assessments of alcohol/substance use and secondary outcomes of depression, anxiety, and mindfulness. RESULTS: Forty-seven percent of veterans attended ≥75 % of sessions. Veterans in both the MBRP and TSF aftercare groups maintained reductions in alcohol and illicit substance use during the aftercare treatment. Nineteen participants (11 %; 19/174) reported returning to alcohol use during the study treatment period and the study found no difference between study groups [MBRP: 9 % vs. TSF 13 %; p = 0.42]. Thirteen participants (7.5 %; 13/174) reported a return to illicit substance use during study treatment [MBRP: 5.4 % vs. TSF 10.3 % p = 0.34]. The number of days of drinking and illicit substance use was not different between groups (alcohol, p = 0.53; illicit substance use, p = 0.28). CONCLUSION: Although retention in treatment limits interpretation of the findings, both MBRP and TSF were effective in maintenance of treatment gains following an intensive treatment program for veterans with SUDs. Future studies should focus on strategies to improve treatment participation.

A Double-Blind Randomized Controlled Trial of Doxazosin for Co-Occurring PTSD and Alcohol Use Disorder in Veterans.

Objective: The aim of this study was to determine the efficacy of doxazosin, an α1-adrenergic antagonist, for the treatment of co-occurring posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD).Methods: This 12-week, double-blind, randomized controlled trial of doxazosin (16 mg/d) was conducted between June 2016 and December 2019 at the Ralph H. Johnson VA Medical Center in Charleston, South Carolina. Participants were military veterans (N = 141) who met DSM-5 criteria for current PTSD and AUD and were randomly assigned to receive doxazosin (n = 70) or placebo (n = 71). Primary outcome measures were the Clinician Administered PTSD Scale (CAPS-5), the PTSD Checklist for DSM-5 (PCL-5), and the Timeline Follow-Back (TLFB).Results: Findings from the intent-to-treat analyses revealed that participants in both groups demonstrated statistically significant reductions in CAPS-5 and PCL-5 scores (P < .0001), but, contrary to hypotheses, no significant differences were observed between groups. Percent drinking days and percent heavy drinking days also decreased significantly during treatment, but there were no differences between groups (P < .0001). Abstinence during treatment was significantly higher in the doxazosin versus the placebo group (22% vs 7%, P = .017); however, participants in the doxazosin group consumed a greater number of drinks on drinking days (6.15 vs 4.56, P = .0096). A total of 74.5% of the sample completed the treatment phase, and there were no group differences in retention or adverse events.Conclusions: Doxazosin was safe and tolerable but was not more effective than placebo in reducing PTSD or AUD severity in this dually diagnosed sample. Clinical considerations such as heterogeneity of PTSD and AUD presentation and potential moderators are discussed in the context of future research directions.Trial Registration: ClinicalTrials.gov Identifier: NCT02500602.

Differential prevalence of Adverse Childhood Experiences (ACEs) by gender and substance used in individuals with cannabis, cocaine, opioid, and tobacco use disorders.

Background: Adverse childhood experiences (ACEs) show a graded association with the development of substance use disorders (SUDs) and engagement in risky substance use behaviors. Women are overrepresented among individuals with more severe childhood adversity (≥4 types of ACEs) and may be at particular risk for aberrant substance use.Objectives: To assess the prevalence of ACEs among men and women with cannabis, opioid, cocaine, and tobacco use disorders.Methods: Non-treatment-seeking individuals participating in clinical addiction research at a single site completed the ACE questionnaire and provided a detailed substance use history. Data were analyzed using proportional odds models and logistic regression.Results: Most participants (424/565; 75%) reported at least one ACE, and more than one-quarter (156/565; 27%) reported severe childhood adversity. Relative to men (n = 283), women (n = 282) reported more ACEs (OR = 1.49; p = .01) and more experiences of emotional/physical abuse (OR = 1.52; p = .02), sexual abuse (OR = 4.08; p = .04), and neglect (OR = 2.30; p < .01). Participants in the cocaine (OR = 1.87; n = .01) and opioid (OR = 2.21; p = .01) use disorder, but not cannabis use disorder (OR = 1.46; p = .08), studies reported more severe adversity relative to the tobacco group. Relative to tobacco users, emotional/physical abuse (OR = 1.92; p = .02) and neglect (OR = 2.46; p = .01) scores were higher in cocaine users and household dysfunction scores were higher in opioid users (OR = 2.67; p = .01).Conclusion: The prevalence of ACEs differs with respect to both participant gender and primary substance used. Novel SUD treatment strategies that incorporate ACEs may be uniquely beneficial in specific subpopulations of people with SUDs.

N-acetylcysteine does not alter neurometabolite levels in non-treatment seeking adolescents who use alcohol heavily: A preliminary randomized clinical trial.

Current treatments for adolescent alcohol use disorder (AUD) are mainly psychosocial and limited in their efficacy. As such, pharmacotherapies are being investigated as potential adjunctive treatments to bolster treatment outcomes. N-acetylcysteine is a promising candidate pharmacotherapy for adolescent AUD because of its tolerability and demonstrated ability to modulate glutamatergic, GABAergic, and glutathione systems. The primary objective of this double-blind, placebo-controlled, within-subjects crossover preliminary investigation was to measure potential changes within glutamate + glutamine (Glx), GABA, and glutathione levels in the dorsal anterior cingulate cortex (dACC) using proton magnetic resonance spectroscopy during 10-days of N-acetylcysteine (1200 mg twice daily) compared to 10-days of placebo in non-treatment seeking adolescents who use alcohol heavily (N = 31; 55% female). Medication adherence was confirmed via video. Effects on alcohol use were measured using Timeline Follow-Back as an exploratory aim. Linear mixed effects models controlling for baseline metabolite levels, brain tissue composition, alcohol use, cannabis use, and medication adherence found no significant differences in Glx, GABA, or glutathione levels in the dACC after N-acetylcysteine compared to placebo. There were also no measurable effects on alcohol use; however, this finding was underpowered. Findings were consistent in the subsample of participants who met criteria for AUD (n = 19). The preliminary null findings in brain metabolite levels may be due to the young age of participants, relatively low severity of alcohol use, and non-treatment seeking status of the population investigated. Future studies can use these findings to conduct larger, well-powered studies within adolescents with AUD.

COPE and oxytocin for the treatment of co-occurring PTSD and alcohol use disorder: Design and methodology of a randomized controlled trial in U.S. military veterans.

BACKGROUND: A significant proportion of individuals with alcohol use disorder (AUD) also meet criteria for posttraumatic stress disorder (PTSD). Military veterans are at increased risk for developing co-occurring AUD/PTSD, with prevalence rates 2-4 times higher than the general population. Research is needed to develop more effective treatments for this common comorbidity. The current investigation addresses this need by examining the synergistic effects of a novel pharmacotherapy combined with psychotherapy for co-occurring AUD/PTSD among veterans. Accumulating evidence suggests that the neuropeptide oxytocin (OT) is a promising pharmacotherapy to augment psychotherapy for AUD/PTSD. OT targets neurobiological and behavioral dysregulation common to both AUD and PTSD, in particular, corticolimbic connectivity. Human and animal studies show OT reduces alcohol self-administration, tolerance, and withdrawal; enhances fear extinction; and promotes prosocial behaviors. The current study builds on previous work by examining OT among veterans with AUD/PTSD receiving Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE), an evidence-based integrated treatment. METHODS: This paper describes the rationale, design, and methodology of a Stage II, 12-week, double-blind, randomized clinical trial of intranasal OT (40 IU) versus placebo combined with COPE among veterans (N = 180) with current AUD/PTSD. In addition, the effects of treatment on corticolimbic connectivity will be examined using functional magnetic resonance imaging (fMRI) at pre- and post-treatment. CONCLUSIONS: The proposed study will provide new knowledge and mechanistic insights to accelerate research in this understudied area and may lead to improved treatment outcomes for co-occurring AUD/PTSD. CLINICALTRIALS: gov: NCT04523922.

Early intervention using written exposure therapy for PTSD and AUD symptoms following sexual assault: Description of design and methodology.

The co-occurrence of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is common following sexual assault and associated with more severe symptomology and increased likelihood of sexual revictimization. Integrated interventions aimed at reducing PTSD and AUD symptoms following recent sexual assault are needed and should address barriers to care and early treatment termination. The proposed study will test a novel, brief (5 to 7 sessions) intervention that integrates Written Exposure Therapy for PTSD and Cognitive Behavioral Therapy for AUD, and is initiated within the first six weeks post-assault. In Phase 1, qualitative analysis of content gathered during focus groups with treatment providers will be conducted to inform intervention development. In Phase 2, a proof-of-concept pilot study (n = 10) of the intervention, Substance Use Skills Training and Exposure Post-Sexual Assault (STEPS), will be conducted. In Phase 3, a pilot randomized controlled trial (RCT) among 54 recent sexual assault survivors will be implemented using the updated manualized STEPS intervention to evaluate feasibility and preliminary efficacy in reducing PTSD and AUD symptoms. Ecological momentary assessments will be used to assess daily alcohol use, craving, affect, intrusions and avoidance. The effects of STEPS on commonly associated symptoms (e.g., depression, substance use) will be examined. The proposed study has the potential to make a significant public health impact by advancing knowledge on the link between sexual assault and co-occurring PTSD and AUD and informing early intervention efforts for this high-risk population.

Automatically identifying opioid use disorder in non-cancer patients on chronic opioid therapy.

Background: Using the International Classification of Diseases (ICD) codes alone to record opioid use disorder (OUD) may not completely document OUD in the electronic health record (EHR). We developed and evaluated natural language processing (NLP) approaches to identify OUD from the clinal note. We explored the concordance between ICD-coded and NLP-identified OUD.Methods: We studied EHRs from 13,654 (female: 8223; male: 5431) adult non-cancer patients who received chronic opioid therapy (COT) and had at least one clinical note between 2013 and 2018. Of eligible patients, we randomly selected 10,218 (75%) patients as the training set and the remaining 3436 patients (25%) as the test dataset for NLP approaches.Results: We generated 539 terms representing OUD mentions in clinical notes (e.g., "opioid use disorder," "opioid abuse," "opioid dependence," "opioid overdose") and 73 terms representing OUD medication treatments. By domain expert manual review for the test dataset, our NLP approach yielded high performance: 98.5% for precision, 100% for recall, and 99.2% for F-measure. The concordance of these NLP and ICD identified OUD was modest (Kappa = 0.63).Conclusions: Our NLP approach can accurately identify OUD patients from clinical notes. The combined use of ICD diagnostic code and NLP approach can improve OUD identification.

Sex and drug differences in stress, craving and cortisol response to the trier social stress task.

RATIONALE: The hypothalamic-pituitary-adrenal (HPA) axis is a critical hormonal system involved in stress response. A number of studies have investigated the HPA axis response of drug-dependent individuals to stressors. Stress-induced vulnerabilities in the HPA axis may differ in response to chronic use of different substances, possibly leading to different target therapies. There has not been a direct comparison of HPA axis and subjective response between individuals with different types of substance use disorders following a laboratory stress intervention. OBJECTIVES: The primary goal of the current study was to compare subjective and neuroendocrine response to the Trier Social Stress Task (TSST) across multiple primary types of substance use disorders and investigate differential response between males and females. METHODS: Four hundred participants were drawn from seven studies completed at the Medical University of South Carolina between 2011 and 2021. The TSST was utilized across studies and subjective and neuroendocrine responses measured following completion. Generalized linear mixed effects models and area under the response curve analysis were used to compare both substance type and sex differences. RESULTS: The study groups involving individuals with cocaine use disorder had blunted stress, craving and cortisol response following the TSST as compared to other substance use groups. Females in the cocaine groups reported higher subjective stress but lower cortisol than males. CONCLUSIONS: The study results indicate that there may be differential effects of substances on the HPA axis, with cocaine using individuals exhibiting more blunting of the HPA axis response as compared to users of other substances.

The Drug Abuse Research Training (DART) Program for Psychiatry Residents and Summer Fellows: 15-Year Outcomes.

OBJECTIVE: To increase the number of physician-scientists in research, the Drug Abuse Research Training (DART) program at the Medical University of South Carolina offers a 2-year research track for psychiatry residents and a 10-week summer fellowship for students. The goal of this study was to examine program outcomes and alumni diversity levels over DART's 15-year history. METHODS: To date, 215 trainees (44 residents, 171 summer fellows) have completed the program. An anonymous online survey was sent to the 143 program alumni with valid contact information. Survey data included demographic characteristics, post-program research involvement, and self-reported barriers to continued research engagement. RESULTS: Overall survey completion response was 83.5% (N = 122). The alumni included 59.0% women, and 36.1% of respondents identified as a member of a minority racial/ethnic group. Following program completion, 77.0% of the alumni reported continued research involvement. More than half of the alumni reported scientific publications (57.4%) and conference presentations (63.1%) since completing DART. Among respondents who did not subsequently engage in research, the most common modifiable barriers included difficulty finding a mentor, self-perceived deficits in statistical skills and research methodology, and overall lack of confidence in research ability. CONCLUSIONS: Over the past 15 years, the DART program has established a diverse research training program that now spans the educational spectrum from undergraduate to residency training. Future program goals include additional training to address self-reported modifiable research barriers. This program provides a model for other training programs designed to cultivate research interests and promote the diversity of clinical researchers.

Effects of intranasal oxytocin on threat- and reward-related functional connectivity in men and women with and without childhood abuse-related PTSD.

Novel treatments that target neurobiological alterations associated with childhood trauma, particularly among those with posttraumatic stress disorder (PTSD), could mitigate negative outcomes for these at-risk individuals. PTSD is characterized by abnormalities within the brain's salience network and reward circuitry, which are modulated by intranasal oxytocin. Using a double-blind, randomized, placebo-controlled crossover design, we tested whether intranasal oxytocin (24 international units) influenced functional coupling of the amygdala with the anterior insula (AI), dorsal anterior cingulate cortex, and nucleus accumbens in response to implicitly presented fearful, angry, and happy faces among childhood trauma-exposed individuals with (n = 16, 9 women) and without PTSD (n = 18, 12 women). Psychophysiological interaction analyses revealed that oxytocin effects were limited to amygdala-AI connectivity in the fear condition, distinct for men and women, and not impacted by PTSD diagnosis. In response to fear faces, oxytocin reduced left amygdala-left AI connectivity for women but not men; reduced left amygdala-right AI connectivity among women, but increased this connectivity in men; and reduced right amygdala-right anterior insula connectivity for men, but increased it for women. Results suggest that intranasal oxytocin modulates threat salience among childhood trauma-exposed individuals and that these effects vary as a function of gender and hemisphere.