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Dialectical Behaviour Therapy (DBT) has demonstrated effectiveness in reducing harmful behaviours associated with emotion dysregulation, including non-suicidal self-injury (NSSI) and binge eating. It has been hypothesized that the effects of DBT on NSSI and binge eating are the result of improvements in emotion regulation (ER); however, the extent to which changes in ER account for reductions in these behaviours is unclear. The present study leverages two unique clinical samples to examine the degree to which changes in ER influence changes in the frequency of NSSI and binge eating over the course of DBT. Participants included 189 Veterans receiving outpatient DBT and 117 civilians enrolled in a DBT Intensive Outpatient Program. Analyses examined changes in ER, binge eating and NSSI over the course of treatment, as well as the extent to which NSSI and binge eating frequency were influenced by changes in ER. In the Veteran sample, DBT led to improvements in ER abilities and significant reductions in NSSI and binge eating; however, changes in ER did not account for observed reductions in NSSI or binge eating. In the civilian sample, the effects of DBT on ER, NSSI and binge eating were nonsignificant. Our findings suggest that ER may not be the only mechanism through which DBT exerts its effects on NSSI and binge eating. The effects of DBT on ER and self-damaging behaviours may vary based on factors such as treatment setting, time in treatment and clinical severity of the sample., (© 2024 John Wiley & Sons Ltd.)

Background: Metabotropic glutamate receptor 5 (mGlu5) dysregulation has been implicated in the pathophysiology of trauma-related psychopathology, and there are direct interactions between the endocannabinoid and glutamatergic systems. However, relationships between cannabis use (CU) and mGlu5 have not been directly investigated in trauma-related psychopathology., Methods: Using positron emission tomography with [18F]FPEB, we examined relationships between CU status and mGlu5 availability in vivo in a cross-diagnostic sample of individuals with trauma-related psychopathology (n = 55). Specifically, we tested whether mGlu5 availability in frontolimbic regions of interest (ROIs; dorsolateral prefrontal cortex, orbitofrontal cortex, ventromedial prefrontal cortex, amygdala, hippocampus) differed as a function of CU status., Results: Past-year CU (n = 22) was associated with 18.62%-19.12% higher mGlu5 availability in frontal and 14.24%-16.55% higher mGlu5 in limbic ROIs relative to participants with no recent CU. Similarly, past-month or monthly CU (n = 16) was associated with higher mGlu5 availability in frontal (18.05%-20.62%) and limbic (15.53%-16.83%) ROIs. mGlu5 availability in the orbitofrontal cortex and amygdala was negatively associated with depressive symptoms in the past-year CU group. In both CU groups, exploratory analyses showed negative correlations between mGlu5 availability and sadness across all ROIs and with perceptions of worthlessness and past failures (r's = -.47 to .66, P's = .006-.033) in the ventromedial prefrontal cortex. Participants with CU reported lower mean depressive symptoms (P's = .006-.037) relative to those without CU., Conclusions: These findings have substantial implications for our understanding of interactions between CU and glutamatergic neurotransmission in trauma-related psychopathology, underscoring the need for treatment development efforts to consider the effects of CU in this population., (© The Author(s) 2024. Published by Oxford University Press on behalf of CINP.)

Background: The national opioid crisis continues to intensify, despite the fact that opioid use disorder (OUD) is treatable and opioid overdose deaths are preventable through first-line treatment with medications for opioid use disorder (MOUD). This study identifies and categorizes payment-related barriers that impact MOUD access and retention from both the provider and patient perspectives and provides insight into how these barriers can be addressed., Methods: We performed a critical review of the literature (peer-reviewed studies and relevant documents from the gray literature) to identify payment-related access and retention barriers to MOUD. We used the results of this review to develop an analytic framework to understand how payment impacts MOUD access and retention for both providers and patients. In addition, we reviewed action plans developed by Massachusetts communities that participated in the Healing Communities Study (HCS) to analyze which payment-related barriers were addressed through the study., Results: We identified 18 payment-related barriers that patients or providers face when initiating or continuing MOUD with either methadone or buprenorphine in Opioid Treatment Programs (OTP) and non-OTP settings. Patient-related barriers mainly relate to health insurance coverage or the design of health plans (e.g., cost sharing, covered benefits) resulting in direct (medical and non-medical) and indirect costs that can affect both access and retention, especially as they relate to services provided in OTPs. Provider-related barriers include low reimbursement and administrative burden and are most likely to impact access to MOUD. Evidence-based strategies to expand MOUD as part of the HCS in Massachusetts targeted about half of the patient and provider payment-related barriers identified., Conclusion: Patients and providers face an array of payment-related barriers that impact access to and retention on MOUD, most of which relate to inadequate health insurance coverage, features of health plans, and key federal and state policies. As new regulatory policies are enacted that expand access to MOUD, such as greater flexibility in OTPs and MOUD delivered via telehealth, it will be important to align these delivery changes with payment reform involving payers, providers, and policymakers., Competing Interests: Declaration of competing interest No conflicts declared., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Mothers with a history of childhood maltreatment (CM) are particularly vulnerable to postpartum mental health changes. Variability in mental health trajectories is present over the first 18-months postpartum. Little is known about the potentially unique impacts of post-traumatic change or resilience on later postpartum mental health., Methods: Participants (N = 97) completed questionnaires over the first 18-months postpartum measuring demographic risk, mental health symptoms, traumatic experiences, and resilience. Mothers also completed an interview measure coded for post-traumatic changes at 6-months postpartum. Multinomial logistic regression models examined post-traumatic change and resilience factors as predictors of mothers' longitudinal latent mental health trajectory., Results: Three classes of latent postpartum mental health emerged: low-symptom, vulnerable, and chronic high-risk. Mothers reporting stronger positive post-traumatic changes were more likely to be in the low-symptom class than the chronic high-risk class (B = -1.082, p = .01). Mothers reporting stronger negative post-traumatic changes were more likely to be in the vulnerable class (B = 0.778, p = .006) or chronic high-risk class (B = 0.906, p = .046) than the low-symptom class. Resilience was not predictive of mental health class., Limitations: Findings are correlational, and causal effects between post-traumatic growth and mental health symptoms cannot be assumed. Mothers who consented to the interview may not be fully representative of all women who have experienced CM, limiting generalizability of findings., Conclusions: Positive post-traumatic change is associated with reduced psychopathology. These findings may assist in identification of mothers at greater risk of adverse postpartum outcomes and futher inform interventions focused on enhancing positive changes in post-traumatic cognitions., Competing Interests: Declaration of competing interest The authors have no disclosures to make., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Elucidating biological mechanisms contributing to bipolar disorder (BD) is key to improved diagnosis and treatment development. With converging evidence implicating the metabotropic glutamate receptor 5 (mGlu5) in the pathology of BD, here, we therefore test the hypothesis that recently identified deficits in mGlu5 are associated with functional brain differences during emotion processing in BD., Methods: Positron emission tomography (PET) with [ 18 F]FPEB was used to measure mGlu5 receptor availability and functional imaging (fMRI) was performed while participants completed an emotion processing task. Data were analyzed from 62 individuals (33 ± 12 years, 45 % female) who completed both PET and fMRI, including individuals with BD (n = 18), major depressive disorder (MDD: n = 20), and psychiatrically healthy comparisons (HC: n = 25)., Results: Consistent with some prior reports, the BD group displayed greater activation during fear processing relative to MDD and HC, notably in right lateralized frontal and parietal brain regions. In BD, (but not MDD or HC) lower prefrontal mGlu5 availability was associated with greater activation in bilateral pre/postcentral gyri and cuneus during fear processing. Furthermore, greater prefrontal mGlu5-related brain activity in BD was associated with difficulties in psychomotor function (r≥0.904, p≤0.005) and attention (r≥0.809, p≤0.028)., Limitations: The modest sample size is the primary limitation., Conclusions: Deficits in prefrontal mGlu5 in BD were linked to increased cortical activation during fear processing, which in turn was associated with impulsivity and attentional difficulties. These data further implicate an mGlu5-related mechanism unique to BD. More generally these data suggest integrating PET and fMRI can provide novel mechanistic insights., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: People with substance use disorders (SUD) face many barriers to receiving evidence-based treatments including access to and cost of treatment. People who use drugs face stigma that limits access to traditional office-based clinics. With the goal of reducing morbidity and mortality, mobile clinics reduce many of these barriers by providing harm reduction and on-demand low-threshold medical care., Methods: In 2020 Massachusetts Department of Public Health (DPH) Mobile Addiction Services Program expanded a program called Community Care in Reach building on its success in reducing barriers to care and increasing patient encounters. In the current evaluation we conducted site visits to the four new mobile clinics and conducted one individual semi-structured provider interview at each of the four clinics. In addition, we supported a monthly learning collaborative of staff in four agencies involved with this initiative. The current evaluation used the RE-AIM framework to analyze the implementation of the mobile clinics., Results: Clinicians described many challenges and opportunities. The typical patient is unhoused, having a substance use disorder, and disconnected from traditional pathways to care. Clinicians are able to initiate people on buprenorphine largely due to the trust they establish with patients. Referral networks are facilitated by established community linkages. The philosophy of care is patient-centered. Mobile clinics provide a wide range of healthcare services including harm reduction, although finding a location to park and relations with police can be challenging. The workflow is uneven due to the model that is built on unscheduled visits., Conclusion: This study provides insight into how mobile clinics address the gaps in care for persons with OUD and fatal opioid overdoses. Harm reduction services are a critical intervention and financial sustainability of mobile clinics has to be tested., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Dynamic brain immune function in individuals with posttraumatic stress disorder is rarely studied, despite evidence of peripheral immune dysfunction. Positron emission tomography brain imaging using the radiotracer [ 11 C]PBR28 was used to measure the 18-kDa translocator protein (TSPO), a microglial marker, at baseline and 3 h after administration of lipopolysaccharide (LPS), a potent immune activator. Data were acquired in 15 individuals with PTSD and 15 age-matched controls. The PTSD group exhibited a significantly lower magnitude LPS-induced increase in TSPO availability in an a priori prefrontal-limbic circuit compared to controls. Greater anhedonic symptoms in the PTSD group were associated with a more suppressed neuroimmune response. In addition, while a reduced granulocyte-macrophage colony-stimulating factor response to LPS was observed in the PTSD group, other measured cytokine responses and self-reported sickness symptoms did not differ between groups; these findings highlight group differences in central-peripheral immune system relationships. The results of this study provide evidence of a suppressed microglia-mediated neuroimmune response to a direct immune system insult in individuals with PTSD that is associated with the severity of symptoms. They also provide further support to an emerging literature challenging traditional concepts of microglial and immune function in psychiatric disease., Competing Interests: Competing interests statement:J.H.K.: (consultations less than $5,000/y) Aptinyx, Inc., BioXcel, Biogen, Idec, MA, Bionomics, Limited (Australia), Boehringer Ingelheim International, Cerevel Pharmaceuticals, Epiodyne, Inc., Esai, Inc., Janssen Research & Development, Jazz Pharmaceuticals, Inc., Otsuka America Pharmaceutical, Inc., PsychoGenics, Inc., Sunovion Pharmaceuticals, Inc., Takeda Pharmaceuticals (Stock/Options) Biohaven Pharmaceuticals, Cartego Therapeutics, Damona Pharmaceuticals, Delix Therapeutics, Inc., EpiVario, Inc., Freedom Biosciences, Neumora Therapeutics, Inc., Response Pharmaceuticals, Rest Therapeutics, Spring Health, Inc., Tempero Bio, Inc., Terran Biosciences, Tetricus Inc. (nonmonetary support, i.e., provision of drug) Cerevel Pharmaceuticals, Novartis. J.H.K. stands to benefit from patents held by Yale University that were licensed to Janssen Pharmaceuticals (ketamine), Biohaven Pharmaceuticals (riluzole), Freedom Biosciences (NMDA-R antagonist plus MTORC inhibitor), and Spring Health (precision medicine strategy).

Atrial fibrillation (AFib) is the most common cardiac rhythm disturbance, often treated via electrical cardioversion. Following rhythm restoration, a period of depressed mechanical function known as atrial stunning occurs, suggesting that defects in contractility occur in AFib and are revealed upon restoration of rhythm. This project aims to define the contractile remodeling that occurs in AFib. To assess contractile function, we used a canine atrial tachypacing model of induced AFib. Mass spectrometry analysis showed dysregulation of contractile proteins in samples from AFib compared with sinus rhythm atria. Atrial cardiomyocytes show reduced force of contraction, decreased resting tension, and increased calcium sensitivity in skinned single cardiomyocyte studies. These alterations correlated with degradation of myofilament proteins including myosin heavy chain altering force of contraction, titin altering resting tension, and troponin I altering calcium sensitivity. We measured degradation of other myofilament proteins, including cardiac myosin binding protein C and actinin, that show degradation products in the AFib samples that are absent in the sinus rhythm atria. Many of the degradation products appeared as discrete cleavage products that are generated by calpain proteolysis. We assessed calpain activity and found it to be significantly increased. These results provide an understanding of the contractile remodeling that occurs in AFib and provide insight into the molecular explanation for atrial stunning and the increased risk of atrial thrombus and stroke in AFib. NEW & NOTEWORTHY Atrial fibrillation is the most common cardiac rhythm disorder, and remodeling during atrial fibrillation is highly variable between patients. This study has defined the biophysical changes in contractility that occur in atrial fibrillation along with identifying potential molecular mechanisms that may drive this remodeling. This includes proteolysis of several myofilament proteins including titin, troponin I, myosin heavy chain, myosin binding protein C, and actinin, which is consistent with the observed contractile deficits.

Since the inception of the Higher Education Opportunity Act in 2008, there has been an increase in the number of post-secondary education institutions in the United States that have established inclusive postsecondary programs for individuals with intellectual disabilities to attend college and achieve higher levels of employment. Previous studies have investigated the development and outcomes of these programs, however, less has been explored related to professors' experiences and perceptions regarding this unique student population, particularly within Hispanic Serving Institutions (HSI). The current study focused on professors teaching inclusive courses within a new Comprehensive Transition and Postsecondary Program at a HSI and aimed to identify their perceptions and experiences related to instructing students with intellectual disabilities. Six professors participated in pre- and post-semester in-depth interviews. Findings from applied thematic analysis included: (a) barriers to success; (b) academic supports and strategies; (c) successful outcomes and (d) considerations for future, related programming.

EBNA1 is an Epstein Barr virus (EBV) protein expressed in all EBV-associated cancers. EBNA1 plays a critical role in the replication and maintenance of EBV episomes in latently infected cells. VK-2019 was developed as a highly specific inhibitor of EBNA1 DNA binding activity and is currently in phase 1 development as a treatment for EBV-associated carcinomas. A sensitive and reliable method was developed to quantify VK-2019 in human plasma using liquid chromatography with tandem mass spectrometry to perform detailed pharmacokinetic studies. VK-2019 was extracted from plasma using protein precipitation with acetonitrile. Separation of VK-2019, two purported metabolites, and the internal standard, VK-2019-d6, was achieved with a Zorbax XDB C 18 column using a gradient flow over 6 min. VK-2019 was detected using a SCIEX 4500 triple quadrupole mass spectrometer operating in positive electrospray ionization mode. The assay range was 0.5-500 ng/mL and proved to be accurate and precise. Dilutions of 1:10 were accurately quantified. VK-2019 was stable in plasma at -70°C for approximately 18 months. The method was applied to assess the total plasma concentrations of VK-2019 in a patient who received a single and multiple oral daily doses of 120 mg., (© 2023 John Wiley & Sons Ltd.)

Background: Understanding distinct neurobiological mechanisms underlying bipolar disorder (BD) and major depressive disorder (MDD) is crucial for accurate diagnosis and the discovery of novel and more effective targeted treatments. Previous diffusion-weighted MRI studies have suggested some common frontotemporal corticolimbic system white matter (WM) abnormalities across the disorders. However, critical to the development of more precise diagnosis and treatment is identifying distinguishing abnormalities. Promising candidates include more prominent frontotemporal WM abnormalities observed in BD in the uncinate fasciculus (UF) that have been associated with frontal-amygdala functional dysconnectivity, and with suicide that is especially high in BD. Prior work also showed differentiation in metabotropic glutamate receptor 5 (mGlu5) abnormalities in BD versus MDD, which could be a mechanism affected in the frontotemporal system. However, associations between WM and mGlu5 have not been examined previously as a differentiator of BD. Using a multimodal neuroimaging approach, we examined WM integrity alterations in the disorders and their associations with mGluR5 levels., Methods: Individuals with BD ( N  = 21), MDD ( N  = 10), and HC ( N  = 25) participated in structural and diffusion-weighted MRI scanning, and imaging with [ 18 F]FPEB PET for quantification of mGlu5 availability. Whole-brain analyses were used to assess corticolimbic WM matter fractional anisotropy (FA) across BD and MDD relative to HC; abnormalities were tested for associations with mGlu5 availability., Results: FA corticolimbic reductions were observed in both disorders and altered UF WM integrity was observed only in BD. In BD, lower UF FA was associated with lower amygdala mGlu5 availability ( p  < .05)., Conclusions: These novel preliminary findings suggest important associations between lower UF FA and lower amygdala mGlu5 levels that could represent a disorder-specific neural mechanism in which mGluR5 is associated with the frontotemporal dysconnectivity of the disorder., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Borderline personality disorder (BPD) is a serious and understudied mental health condition associated with profound personal and public health consequences. Methodological differences in characterizing BPD may limit understanding the scope of the disorder's prevalence and effect. For example, using different diagnostic rules for BPD can affect apparent prevalence, comorbidity, and clinical presentation. This study examined how differences in diagnostic rules used to assign BPD diagnosis impacted its prevalence and associations with clinically relevant variables (e.g., demographics, comorbidity, treatment-seeking). Participants were a nationally representative sample of 36,309 noninstitutionalized U.S. adults. All variables were assessed via clinical interview (Alcohol Use Disorder and Associated Disabilities Interview Schedule-5). Six diagnostic rules determined BPD status. We used frequencies to examine prevalence rates of and associations between BPD and other clinical variables, and logistic regressions to examine the associations between each BPD variable and the other outcomes. The prevalence of BPD ranged widely-from 0.5% to 11.4%-per the diagnostic rule used. Associations between BPD diagnosis and various outcomes and clinical variables generally remained stable across all diagnostic rules, though effects became more extreme as diagnostic rules became more restrictive. Additionally, meaningful differences emerged as a function of the number of items used (30 vs. 18 items) even with no other changes to diagnostic rules. The field examining BPD and associated problem behaviors should critically consider how to most effectively characterize BPD to understand these problems more accurately and optimize the generalizability of findings. (PsycInfo Database Record (c) 2024 APA, all rights reserved).