Impaired Endogenous Neurosteroid Signaling Contributes to Behavioral Deficits Associated With Chronic Stress.

BACKGROUND: Chronic stress is a major risk factor for psychiatric illnesses, including depression. However, the pathophysiological mechanisms whereby stress leads to mood disorders remain unclear. Allopregnanolone acts as a positive allosteric modulator preferentially on δ subunit-containing GABAA (gamma-aminobutyric acid A) receptors. Accumulating clinical and preclinical evidence supports the antidepressant effects of exogenous administration of allopregnanolone analogs; yet, the role of endogenous allopregnanolone in the pathophysiology of depression remains unknown. METHODS: We utilized a chronic unpredictable stress (CUS) mouse model, followed by behavioral and biochemical assays, to examine whether altered neurosteroid signaling contributes to behavioral outcomes following CUS. We subsequently performed in vivo CRISPR (clustered regularly interspaced short palindromic repeats) knockdown of rate-limiting enzymes involved in allopregnanolone synthesis, 5α-reductase type 1 and 2 (5α1/2), in addition to lentiviral overexpression of 5α1/2 in the basolateral amygdala (BLA) of mice that underwent CUS to assess the impact of 5α1/2 on behavioral outcomes. RESULTS: The expression of δ subunit-containing GABAA receptors and endogenous levels of allopregnanolone were reduced in the BLA following CUS. Treatment with an exogenous allopregnanolone analog, SGE-516, was sufficient to increase allopregnanolone levels in the BLA following CUS. Knockdown of 5α1/2 in the BLA mimicked the behavioral outcomes associated with CUS. Conversely, overexpression of 5α1/2 in the BLA improved behavioral outcomes following CUS. CONCLUSIONS: Our findings demonstrate that chronic stress impairs endogenous neurosteroid signaling in the BLA, which is sufficient to induce behavioral deficits. Further, these studies suggest that allopregnanolone-based treatments may directly target the underlying pathophysiology of mood disorders suggesting that targeting endogenous neurosteroidogenesis may offer a novel therapeutic strategy.

Sexual health knowledge and stigma in a community sample of HIV-positive gay, bisexual and other men who have sex with men in Puerto Rico.

Gay, bisexual and other men who have sex with men (GBMSM) are at increased risk for HIV infection and disease progression. Also, HIV-positive GBMSM are among those less likely to be retained in care. In this study we analyzed sexual health knowledge (SHK) and various manifestations of stigma in a community sample of HIV-positive GBMSM in Puerto Rico. The sample reports overall low SHK scores, and lower score were associated with low educational attainment, unemployment, low income, and with self-identifying heterosexual participants. Almost half of the sample reported moderate to severe perceived gay stigma, 68.4% reported moderate to severe hidden-gay stigma, and 30.6% reported moderate to severe HIV-felt stigma. Further research is recommended to obtain culturally congruent information and develop interventions addressing the multiple layers of stigma in the social context where the interventions will be delivered.

Discrimination and Health among Lesbian, Gay, Bisexual and Trans People in Puerto Rico.

OBJECTIVE: To identify the experiences of discrimination among and the perceived priorities for the health of lesbian, gay, bisexual, and trans (LGBT) people in Puerto Rico (PR). METHODS: Data were collected during the 2013 LGBT Pride Parade in San Juan, using a brief self-administered survey that included questions on sociodemographic characteristics, the disclosure of sexual orientation/gender identity, experiences of discrimination, experiences while receiving social and health services, and perceived healthcare priorities and needs. RESULTS: Most participants reported that they had disclosed their sexual orientation to at least one person. Discrimination due to sexual orientation/gender identity was most frequently reported to have occurred in school settings. At least 25% of the sample reported regular or negative experiences based on sexual orientation/gender identity when receiving government services and when looking for support from relatives. HIV/AIDS, mental health, and sexual health were identified as healthcare priorities. In bivariate analyses, mental health services and aging were the priorities most frequently reported among older participants. HIV/AIDS was the main priority only for gay men; sexual health was the main priority for bisexuals; and mental health was the main priority for lesbians. Most participants reported that their preferred modalities for health service provision were support groups and health education. CONCLUSION: The experiences of discrimination among LGBT people in PR were consistent across age groups and sexual orientation/gender identity. Policies and interventions to address discrimination in different settings are necessary. The findings also suggest the need to prioritize HIV services among gay men and to address mental and sexual health needs among lesbian and bisexual people.

Sexual health and socioeconomic-related factors among HIV-positive men who have sex with men in Puerto Rico.

Most of the research among HIV-positive populations has been approached from behavioral risk models. This is particularly true for those otherwise socially vulnerable groups like men who have sex with men (MSM). As a response to this pattern, we examined data from an ongoing health promotion research being conducted in Puerto Rico (PR). The study is limited to HIV-positive MSM and consists of the participation in a survey interview that includes domains used to assess indicators of socio-economic-related factors (age, educational level, employment, religion, and partnership status) and sexual health (sexual satisfaction, condom use, and sexual health knowledge(SHK)). Participants reported a relatively high level (75 %) of sexual satisfaction and inconsistent condom use (50.9 % reported always using a condom). A deficient (61 %) SHK was also reported. In multivariate analyses, a higher educational level was associated with higher sexual satisfaction (aß = 3.223; 95 % CI 0.291-6.156) and higher levels of SHK (aß = 1.328; 95 % CI 0.358-2.297), while unemployment was associated with less condom use (aOR 0.314; 95 % CI 0.122-0.810). Not having a primary sexual partner was associated with less sexual satisfaction (aß = -3.871; 95 % CI -7.534-0.208) and more condom use (aOR 4.292; 95 % CI 1.310-14.068). Findings support the notion that men of a disadvantaged socioeconomic position may have a poorer sexual health status; with a lower level of education and unemployment leading this disparity. Findings also evidence that partnership status may have a role in the sexual health of HIV-positive MSM. To our knowledge, this is the first comprehensive analysis of sexual health and socioeconomic indicators among Hispanic/Latino HIV-positive MSM in PR and in the Caribbean. Findings provide valuable information to address the sexual health needs of an underserved population.