The Moderating Effects of HIV Relevant Factors on the Relationship Between Intimate Partner Violence and Intention to Start HIV Pre-exposure Prophylaxis (PrEP) Among Cisgender Women.

Intimate partner violence (IPV) and HIV are serious and related public health problems that detrimentally impact women's health. Because women who experience IPV are more likely to acquire HIV, it is critical to promote HIV prevention strategies, such as HIV pre-exposure prophylaxis (PrEP), that increase autonomy. This study of cisgender women eligible for HIV PrEP took place between 2017 and 2019 in Philadelphia and New York City. This study aimed to examine the relationship between four types of IPV (control, psychological, physical, sexual) and intention to start PrEP among PrEP-eligible cisgender women and assess the extent to which HIV relevant factors moderated the association between IPV experience and intention to start PrEP. In this sample of PrEP-eligible women (n = 214), 68.7% indicated intention to start PrEP in the next 3 months. Ethnicity was strongly associated with intention to start PrEP, with Hispanic women having the highest odds of intending to start PrEP in the next 3 months. Having a controlling partner significantly predicted intention to start PrEP. Women with more than one sex partner and a controlling partner had higher odds of intending to start PrEP as compared with those who had one or no partners and had no IPV control. These findings point to a need for patient-centered interventions that address the need for safety and autonomy among cisgender, PrEP-eligible women.

Correlates of Risk for Disinhibited Behaviors in the Million Veteran Program Cohort.

Importance: Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans' health, such as suicide-related behaviors and substance use disorders (SUDs). Objective: To explore correlates of risk for EXT disorders within the Veterans Health Administration (VA) Million Veteran Program (MVP). Design, Setting, and Participants: A series of phenome-wide association studies (PheWASs) of polygenic risk scores (PGSs) for EXT disorders was conducted using electronic health records. First, ancestry-specific PheWASs of EXT PGSs were conducted in the African, European, and Hispanic or Latin American ancestries. Next, a conditional PheWAS, covarying for PGSs of comorbid psychiatric problems (depression, schizophrenia, and suicide attempt; European ancestries only), was performed. Lastly, to adjust for unmeasured confounders, a within-family analysis of significant associations from the main PheWAS was performed in full siblings (European ancestries only). This study included the electronic health record data from US veterans from VA health care centers enrolled in MVP. Analyses took place from February 2022 to August 2023 covering a period from October 1999 to January 2020. Exposures: PGSs for EXT, depression, schizophrenia, and suicide attempt. Main Outcomes and Measures: Phecodes for diagnoses derived from the International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification, codes from electronic health records. Results: Within the MVP (560 824 patients; mean [SD] age, 67.9 [14.3] years; 512 593 male [91.4%]), the EXT PGS was associated with 619 outcomes, of which 188 were independent of risk for comorbid problems or PGSs (from odds ratio [OR], 1.02; 95% CI, 1.01-1.03 for overweight/obesity to OR, 1.44; 95% CI, 1.42-1.47 for viral hepatitis C). Of the significant outcomes, 73 (11.9%) were significant in the African results and 26 (4.5%) were significant in the Hispanic or Latin American results. Within-family analyses uncovered robust associations between EXT PGS and consequences of SUDs, including liver disease, chronic airway obstruction, and viral hepatitis C. Conclusions and Relevance: Results of this cohort study suggest a shared polygenic basis of EXT disorders, independent of risk for other psychiatric problems. In addition, this study found associations between EXT PGS and diagnoses related to SUDs and their sequelae. Overall, this study highlighted the potential negative consequences of EXT disorders for health and functioning in the US veteran population.

HIV risk perception, pre-exposure prophylaxis (PrEP) awareness, and PrEP initiation intention among women who use drugs.

INTRODUCTION: Women who use drugs (WWUD) are prime candidates for pre-exposure prophylaxis (PrEP) due to their elevated risk of acquiring HIV through biological, behavioral, and contextual factors. However, PrEP uptake among WWUD remains low. The relationship between unhealthy drug use and correlates of PrEP uptake in this vulnerable population is not well defined. The purpose of this study is to characterize the relationships between specific types and routes of drug use and several precursors of PrEP uptake among WWUD. METHODS: The study collected data via a computer-based survey from 233 women living in New York City and Philadelphia who participated in a study designed to develop and pilot a women-focused intervention for PrEP uptake. The sample of cisgender, HIV-negative women were not currently taking PrEP but considered PrEP eligible. This analysis is focused on women's HIV risk perception, PrEP awareness, PrEP initiation intention, and any use of the following drugs: barbiturates, benzodiazepines, crack cocaine, powder cocaine, hallucinogens, heroin, methamphetamines, and prescription opioids. RESULTS: Within the three months prior to study enrollment, 63.1 % of participants reported any drug use; 42 % reported polydrug use; 19.8 % had injected drugs; 75 % reported getting high or drunk before sex; and 44 % had been enrolled in drug treatment. Of our total sample, 41.2 % perceived themselves at risk for HIV infection, 41.6 % were aware of PrEP prior to the study, and 62.7 % intended to initiate PrEP after they were informed. When compared to other PrEP-eligible women, women who reported prescription opioid use and polydrug use perceived themselves at higher risk for HIV infection and had higher intention to start PrEP. However, they and women who reported injecting drugs also reported lower awareness of PrEP. CONCLUSION: These findings have implications for increasing education about PrEP and the various modes of HIV exposure to support PrEP uptake in this vulnerable population.

Correlates of Risk for Disinhibited Behaviors in the Million Veteran Program Cohort.

Background: Many psychiatric outcomes are thought to share a common etiological pathway reflecting behavioral disinhibition, generally referred to as externalizing disorders (EXT). Recent genome-wide association studies (GWAS) have demonstrated the overlap between EXT and important aspects of veterans' health, such as suicide-related behaviors, substance use disorders, and other medical conditions. Methods: We conducted a series of phenome-wide association studies (PheWAS) of polygenic scores (PGS) for EXT, and comorbid psychiatric problems (depression, schizophrenia, and suicide attempt) in an ancestrally diverse cohort of U.S. veterans (N = 560,824), using diagnostic codes from electronic health records. We conducted ancestry-specific PheWASs of EXT PGS in the European, African, and Hispanic/Latin American ancestries. To determine if associations were driven by risk for other comorbid problems, we performed a conditional PheWAS, covarying for comorbid psychiatric problems (European ancestries only). Lastly, to adjust for unmeasured confounders we performed a within-family analysis of significant associations from the main PheWAS in full-siblings (N = 12,127, European ancestries only). Results: The EXT PGS was associated with 619 outcomes across all bodily systems, of which, 188 were independent of risk for comorbid problems of PGS. Effect sizes ranged from OR = 1.02 (95% CI = 1.01, 1.03) for overweight/obesity to OR = 1.44 (95% CI = 1.42, 1.47) for viral hepatitis C. Of the significant outcomes 73 (11.9%) and 26 (4.5%) were significant in the African and Hispanic/Latin American results, respectively. Within-family analyses uncovered robust associations between EXT and consequences of substance use disorders, including liver disease, chronic airway obstruction, and viral hepatitis C. Conclusion: Our results demonstrate a shared polygenic basis of EXT across populations of diverse ancestries and independent of risk for other psychiatric problems. The strongest associations with EXT were for diagnoses related to substance use disorders and their sequelae. Overall, we highlight the potential negative consequences of EXT for health and functioning in the US veteran population.

A Randomized Controlled Pilot Study of Just4Us, a Counseling and Navigation Intervention to Promote Oral HIV Prophylaxis Uptake Among PrEP-Eligible Cisgender Women.

HIV pre-exposure prophylaxis (PrEP) uptake among cisgender women in the United States is low. Just4Us, a theory-based counseling and navigation intervention, was evaluated in a pilot randomized controlled trial among PrEP-eligible women (n = 83). The comparison arm was a brief information session. Women completed surveys at baseline, post-intervention, and at three months. In this sample, 79% were Black, and 26% were Latina. This report presents results on preliminary efficacy. At 3 months follow-up, 45% made an appointment to see a provider about PrEP; only 13% received a PrEP prescription. There were no differences in PrEP initiation by study arm (9% Info vs. 11% Just4Us). PrEP knowledge was significantly higher in the Just4Us group at post-intervention. Analysis revealed high PrEP interest with many personal and structural barriers along the PrEP continuum. Just4Us is a promising PrEP uptake intervention for cisgender women. Further research is needed to tailor intervention strategies to multilevel barriers.Clinicaltrials.gov registration NCT03699722: A Women-Focused PrEP Intervention (Just4Us).

RESUMEN: La aceptación de la profilaxis previa a la exposición (PrEP) al VIH entre las mujeres cisgénero en los Estados Unidos es baja. Just4Us, una intervención de asesoramiento y navegación basada en la teoría, se evaluó en un ensayo piloto controlado aleatorizado con mujeres aptas para la PrEP (n = 83). El brazo de comparación fue una breve sesión de información. Las mujeres completaron encuestas al inicio, después de la intervención ya los 3 meses. En la muestra, el 79% eran negros y el 26% eran latinas. Este informe presenta resultados sobre la eficacia preliminar. A los 3 meses de seguimiento, el 45% hizo una cita para ver a un proveedor acerca de la PrEP; solo el 13% recibió una receta de PrEP. No hubo diferencias en el inicio de la PrEP por brazo de estudio (9% Info frente a 11% Just4Us). El conocimiento fue significativamente mayor en el grupo Just4Us después de la intervención. El análisis reveló un alto interés por la PrEP con muchas barreras personales y estructurales a lo largo del continuo de la PrEP. Just4Us es una prometedora intervención de adopción de PrEP para mujeres cisgénero. Se necesita más investigación para adaptar las estrategias de intervención a las barreras multinivel.

Impact of traumatic life events and polygenic risk scores for major depression and posttraumatic stress disorder on Iraq/Afghanistan Veterans.

Traumatic experiences and genetic heritability are among the most widely acknowledged risk factors leading to the development of psychopathology; including posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). The purpose of this study was to investigate if polygenic risk scores (PRS) among Veterans interacted with traumatic stress to predict PTSD and MDD. 1,389 Iraq-Afghanistan military service Veterans from the Mental Illness Research Education and Clinical Center dataset were analyzed. Genome-wide association study (GWAS) statistics were utilized to generate PRS for PTSD (PRSPTSD) and PRS for MDD (PRSMDD) in order to analyze PRS-by-environment (PRSxE) with trauma exposure to predict PTSD and MDD diagnoses. Trauma exposure and PRSPTSD, were independently associated with a current PTSD diagnosis (p < 0.001 and p < 0.001, respectively). The interaction between trauma exposure and PRSMDD to predict a current diagnosis of PTSD trended towards significance (p = 0.053). Stratifying by trauma thresholds, among those within the lowest trauma load, the association of PRSMDD with PTSD was found to be nominally significant (p = 0.03). For a MDD diagnosis, there was a significant association with trauma exposure (p < 0.001); and the association with PRSMDD was found to be nominally significant (p = 0.03). No significant PRSxE effects were found with MDD. Our findings corroborate previous research highlighting trauma exposure, and genetic heritability, as risk factors for the development of PTSD and MDD in a Veteran population. Additionally, findings suggest that genetic vulnerability may be less important as trauma exposure increases, with high levels of trauma likely to result in PTSD and MDD, regardless of genetic vulnerability.

Adverse childhood experiences, the serotonergic system, and depressive and anxiety disorders in adulthood: A systematic literature review.

BACKGROUND: Recent studies have examined the role that the serotonergic system plays in moderating the association between adverse childhood experiences (ACEs) and depressive and anxiety disorders in adulthood. The aim of this literature review is to synthesize studies that examined serotonin's impact in relation to ACEs, and depressive and anxiety disorders in this population. METHODS: Published studies from 2008 to 2018 were retrieved from PubMed, CINAHL, and PsychINFO databases, and were included if ACEs, the serotonergic system, and depressive and or anxiety disorders were assessed in those with a mean age between nineteen and forty. RESULTS: Twenty-eight studies were included. Various genetic polymorphisms in the serotonergic signaling system moderated the association between ACEs and depression. Additionally, selective serotonin reuptake inhibitors with a high affinity for the serotonin transporter, resulted in poor treatment outcomes for those with history of ACEs. CONCLUSION: Additional research is needed in order to further define the role that the serotonergic genes play in the association between ACEs and depressive and anxiety disorders in adulthood.

Just4Us: Development of a Counselor-Navigator and Text Message Intervention to Promote PrEP Uptake Among Cisgender Women at Elevated Risk for HIV.

ABSTRACT: In the United States, pre-exposure prophylaxis (PrEP) uptake among eligible cisgender women has been slow, despite the availability of oral PrEP since 2012. Although women make up nearly 20% of those living with HIV, there are currently few PrEP uptake interventions for cisgender women at elevated risk for acquiring HIV. Here we describe the process used to design and pre-pilot test Just4Us, a theory-based behavioral intervention to promote PrEP initiation and adherence among PrEP-eligible cisgender women. This work was part of a multiphase study conducted in New York City and Philadelphia, two locations with HIV rates higher than the national average. The counselor-navigator component of the intervention was designed to be delivered in a 60- to 90-min in-person session in the community, followed by several phone calls to support linkage to care. An automated text messaging program was also designed for adherence support. Just4Us addressed personal and structural barriers to PrEP uptake using an empowerment framework by building on women's insights and resources to overcome barriers along the PrEP cascade. Usability pre-pilot testing results were favorable and provided valuable feedback used to refine the intervention.

GABA neurons in the nucleus tractus solitarius express GLP-1 receptors and mediate anorectic effects of liraglutide in rats.

The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is approved for the treatment of obesity; however, there is still much to be learned regarding the neuronal sites of action that underlie its suppressive effects on food intake and body weight. Peripherally administered liraglutide in rats acts in part through central GLP-1Rs in both the hypothalamus and the hindbrain. Here, we extend findings supporting a role for hindbrain GLP-1Rs in mediating the anorectic effects of liraglutide in male rats. To dissociate the contribution of GLP-1Rs in the area postrema (AP) and the nucleus tractus solitarius (NTS), we examined the effects of liraglutide in both NTS AAV-shRNA-driven Glp1r knockdown and AP-lesioned animals. Knockdown of NTS GLP-1Rs, but not surgical lesioning of the AP, attenuated the anorectic and body weight-reducing effects of acutely delivered liraglutide. In addition, NTS c-Fos responses were maintained in AP-lesioned animals. Moreover, NTS Glp1r knockdown was sufficient to attenuate the intake- and body weight-reducing effects of chronic daily administered liraglutide over 3 weeks. Development of improved obesity pharmacotherapies requires an understanding of the cellular phenotypes targeted by GLP-1R agonists. Fluorescence in situ hybridization identified Glp1r transcripts in NTS GABAergic neurons, which when inhibited using chemogenetics, attenuated the food intake- and body weight-reducing effects of liraglutide. This work demonstrates the contribution of NTS GLP-1Rs to the anorectic potential of liraglutide and highlights a phenotypically distinct (GABAergic) population of neurons within the NTS that express the GLP-1R and are involved in the mediation of liraglutide signaling.

Combined Amylin/GLP-1 pharmacotherapy to promote and sustain long-lasting weight loss.

A growing appreciation of the overlapping neuroendocrine mechanisms controlling energy balance has highlighted combination therapies as a promising strategy to enhance sustained weight loss. Here, we investigated whether amylin- and glucagon-like-peptide-1 (GLP-1)-based combination therapies produce greater food intake- and body weight-suppressive effects compared to monotherapies in both lean and diet-induced obese (DIO) rats. In chow-maintained rats, systemic amylin and GLP-1 combine to reduce meal size. Furthermore, the amylin and GLP-1 analogs salmon calcitonin (sCT) and liraglutide produce synergistic-like reductions in 24 hours energy intake and body weight. The administration of sCT with liraglutide also led to a significant enhancement in cFos-activation in the dorsal-vagal-complex (DVC) compared to mono-therapy, suggesting an activation of distinct, yet overlapping neural substrates in this critical energy balance hub. In DIO animals, long-term daily administration of this combination therapy, specifically in a stepwise manner, results in reduced energy intake and greater body weight loss over time when compared to chronic mono- and combined-treated groups, without affecting GLP-1 receptor, preproglucagon or amylin-receptor gene expression in the DVC.

Binge Eating Disorder and Youth.

Children and adolescents who eat unusually large amounts of food, feel guilty about it, and try to hide their overeating may be struggling with binge eating disorder (BED), a condition associated with suicidal ideation and other eating disorders. Although BED is new to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, the syndrome is becoming increasingly recognized. The study of BED in children and adolescents is in its natal phase, but the importance of recognition and possible treatment strategies are discussed in the current article along with psychiatric nursing implications.