Mental health and social connection among older lesbian and bisexual women.

OBJECTIVE: To assess differences in psychosocial and mental health outcomes between older lesbian and bisexual women compared to heterosexual women. DESIGN: Cross sectional study. SETTING: The study was carried out in the California Teachers Study, a prospective cohort study. PARTICIPANTS: Self-identified heterosexual (n = 35,846), lesbian (n = 710), and bisexual (n = 253) women 50 years of age and older were enrolled. MEASUREMENTS: Validated questionnaires were used to measure social connection, overall happiness, and depression. Logistic regression modeling was used to estimate odds ratios (OR) and 95% confidence intervals (CI) comparing lesbian and bisexual women separately to heterosexual women in relation to psychosocial and mental health outcomes. RESULTS: After controlling for age and marital status, older bisexual women were significantly more likely to report lack of companionship (OR = 2.00; 95% CI, 1.30-3.12) and feeling left out (OR = 2.33; 95% CI, 1.36-3.97) compared to older heterosexual women. The odds of reporting feeling isolated from others was significantly higher in lesbian (OR = 1.56; 95% CI, 1.06-2.30) and bisexual women (OR = 2.30; 95% CI, 1.37-3.87) than in heterosexual women. The OR (95% CI) for reporting not being very happy overall was 1.96 (CI, 1.09-3.52) in bisexual women and 1.40 (0.92-2.14) in lesbian women compared to heterosexual women. The likelihood of reporting diagnosed depression was significantly higher in lesbian women (OR = 1.65; 95% CI, 1.38-1.97) and bisexual women (OR = 2.21; 95% CI, 1.67-2.93) compared to heterosexual women. CONCLUSION: Inclusion of lesbian and bisexual women in aging research is essential to understand their unique mental and other health needs, including those specific to bisexual women.

Post-traumatic stress in older, community-dwelling adults with hypertension during the COVID-19 pandemic: An investigation of pre-pandemic sociodemographic, health, and vascular and inflammatory biomarker predictors.

COVID-19 pandemic-related traumatic stress (PRTS) symptoms are reported in various populations, but risk factors in older adults with chronic medical conditions, remain understudied. We therefore examined correlates and pre-pandemic predictors of PRTS in older adults with hypertension during COVID-19. Participants in California, aged 61-92 years (n = 95), participated in a pre-pandemic healthy aging trial and later completed a COVID-19 assessment (May to September 2020). Those experiencing ⩾1 PRTS symptom (n = 40), and those without PRTS symptoms (n = 55), were compared. The PRTS+ group had poorer mental and general health and greater impairment in instrumental activities of daily living. Pre-pandemic biomarkers of vascular inflammation did not predict increased odds of PRTS; however, greater pre-pandemic anxiety and female gender did predict PRTS during COVID-19. Our findings highlight PRTS as a threat to healthy aging in older adults with hypertension; targeted approaches are needed to mitigate this burden, particularly for females and those with pre-existing anxiety.

Association of anxiety and depressive symptoms with C-reactive protein in diverse Latinos: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: High sensitivity C-reactive protein (hsCRP) is a marker of systemic inflammation that has been associated with persistent depressive symptoms. Depression and anxiety are frequently associated with a chronic inflammatory state, yet the nature of this relationship has not been rigorously examined in diverse Hispanic/Latino populations. We aimed to study the association of anxiety and depressive symptoms as well as comorbid presentations, with circulating high sensitivity C-reactive protein (hsCRP) levels in a large Latino cohort of diverse heritages. We hypothesized a significant positive associations of both anxiety and depressive symptoms and hsCRP levels and potential variations among the heritage groups. METHODS: Depressive symptoms and anxiety were measured by the Center for Epidemiological Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI), respectively. Serum hsCRP (hsCRP) levels of 15,448 participants (age 18 to 75 years; 52.3% women) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were measured and categorized based on the established cardiovascular disease (CVD) risk reference values (< 1mg/L, low; 1-<3 mg/L, intermediate; ≥ 3mg/L, high). RESULTS: Mean CES-D, STAI scores, and hsCRP levels were 7.0 (SD = 5.9), 17.0 (SD = 5.7), and 3.84 (SD = 7.85), respectively. Generalized linear modeling, adjusted for sociodemographic characteristics revealed significant associations between depression (exp(ß) = 1.12; p<0.01) and anxiety symptoms (exp(ß) = 1.10; p<0.05) with continuous hsCRP levels. For categorical values of hsCRP, one SD increase in CES-D and STAI scores was associated with a 10% and 8% increase in the RRRs of high vs. low hsCRP, respectively. However, these relationships between CES-D or STAI and hsCRP were no longer statistically significant after adjustment for CVD risk factors and medications. CONCLUSION: We found modest associations between anxiety and depressive symptoms and systemic inflammation measured by hsCRP among diverse Hispanics/Latinos that did not appreciably differ between heritage groups.

G protein-coupled receptors: A target for microbial metabolites and a mechanistic link to microbiome-immune-brain interactions.

Human-microorganism interactions play a key role in human health. However, the underlying molecular mechanisms remain poorly understood. Small-molecules that offer a functional readout of microbe-microbe-human relationship are of great interest for deeper understanding of the inter-kingdom crosstalk at the molecular level. Recent studies have demonstrated that small-molecules from gut microbiota act as ligands for specific human G protein-coupled receptors (GPCRs) and modulate a range of human physiological functions, offering a mechanistic insight into the microbe-human interaction. To this end, we focused on analysis of bacterial metabolites that are currently recognized to bind to GPCRs and are found to activate the known downstream signaling pathways. We further mapped the distribution of these molecules across the public mass spectrometry-based metabolomics data, to identify the presence of these molecules across body sites and their association with health status. By combining this with RNA-Seq expression and spatial localization of GPCRs from a public human protein atlas database, we inferred the most predominant GPCR-mediated microbial metabolite-human cell interactions regulating gut-immune-brain axis. Furthermore, by evaluating the intestinal absorption properties and blood-brain barrier permeability of the small-molecules we elucidated their molecular interactions with specific human cell receptors, particularly expressed on human intestinal epithelial cells, immune cells and the nervous system that are shown to hold much promise for clinical translational potential. Furthermore, we provide an overview of an open-source resource for simultaneous interrogation of bioactive molecules across the druggable human GPCRome, a useful framework for integration of microbiome and metabolite cataloging with mechanistic studies for an improved understanding of gut microbiota-immune-brain molecular interactions and their potential therapeutic use.

Tai Chi versus health education as a frailty intervention for community-dwelling older adults with hypertension.

BACKGROUND: Frailty is associated with poor outcomes among older adults with hypertension and complicates its pharmacological management. Here, we assessed whether 12-weeks of instructor-guided, group Tai Chi (TC) practice improved frailty relative to Healthy Aging Practice-centered Education (HAP-E) classes in older adults with hypertension. METHODS: Secondary analysis of a randomized controlled trial in San Diego County, USA, of 167 community-dwelling individuals aged ≥ 60 yrs (70% female; 72.1 ± 7.5 yrs), defined as non-frail (66%) or frail (34%) based on 53-item deficit accumulation frailty index (FI). Linear mixed-effects models were used to assess pre-to-post intervention differences in FI and logistic regression to explore differential odds of clinically meaningful FI change. RESULTS: One hundred thirty-one participants completed post-intervention assessments. Frailty decreased pre-to-post intervention in the TC (ΔFI = - 0.016, d = - 0.39, - 0.75 to - 0.03), but not the HAP-E arm (ΔFI = - 0.009, d = - 0.13, - 0.52-0.27), despite no significant group differences between the TC and HAP-E arms (d = - 0.11, - 0.46-0.23). Furthermore, greater odds of improved FI were observed for frail participants in the TC (OR = 3.84, 1.14-14.9), but not the HAP-E (OR = 1.34, 0.39-4.56) arm. Subgroup analysis indicated treatment effects in TC were attributed to frail participants (frail: ΔFI = - 0.035, d = - 0.68, -1.26 to - 0.08; non-frail: ΔFI = - 0.005, d = - 0.19, - 0.59-0.22), which was not the case in the HAP-E arm (frail: ΔFI = - 0.017, d = - 0.23, - 0.81-0.35; non-frail: ΔFI = - 0.003, d = - 0.07, - 0.47-0.33). Frail participants were no more likely to drop-out of the study than non-frail (71% vs. 69% retained). CONCLUSIONS: Twelve weeks of twice-weekly guided TC practice was well-tolerated, associated with decreases in frailty, and increased odds of clinically meaningful FI improvement at post-intervention.

A longitudinal study of cannabis use and risk for cognitive and functional decline among older adults with HIV.

Cannabis use is rapidly increasing among older adults in the United States, in part to treat symptoms of common health conditions (e.g., chronic pain, sleep problems). Longitudinal studies of cannabis use and cognitive decline in aging populations living with chronic disease are lacking. We examined different levels of cannabis use and cognitive and everyday function over time among 297 older adults with HIV (ages 50-84 at baseline). Participants were classified based on average cannabis use: frequent (> weekly) (n = 23), occasional (≤ weekly) (n = 83), and non-cannabis users (n=191) and were followed longitudinally for up to 10 years (average years of follow-up = 3.9). Multi-level models examined the effects of average and recent cannabis use on global cognition, global cognitive decline, and functional independence. Occasional cannabis users showed better global cognitive performance overall compared to non-cannabis users. Rates of cognitive decline and functional problems did not vary by average cannabis use. Recent cannabis use was linked to worse cognition at study visits when participants had THC+ urine toxicology-this short-term decrement in cognition was driven by worse memory and did not extend to reports of functional declines. Occasional (≤ weekly) cannabis use was associated with better global cognition over time in older adults with HIV, a group vulnerable to chronic inflammation and cognitive impairment. Recent THC exposure may have a temporary adverse impact on memory. To inform safe and efficacious medical cannabis use, the effects of specific cannabinoid doses on cognition and biological mechanisms must be investigated in older adults.

RESUMEN: El consumo de cannabis está aumentando rápidamente entre los adultos mayores en los Estados Unidos, en parte para tratar síntomas de afecciones de salud comunes (p. ej. dolor crónico, problemas de dormir). Actualmente, hay pocos estudios longitudinales sobre el consumo de cannabis y el deterioro cognitivo en poblaciones que envejecen y viven con enfermedades crónicas. Examinamos diferentes niveles del consumo de cannabis y funciones cognitivas a lo largo del tiempo entre 297 adultos mayores con VIH (de 50 a 84 años al principio de la investigación). Los participantes se clasificaron según el consumo promedio de cannabis: consumidores de cannabis frecuentes (> semanal) (n = 23) ocasionales (≤ semanal) (n = 83), y no consumidores de cannabis (n=191) fueron seguidos longitudinalmente hasta por 10 años (promedio = 3,9 años). Los modelos multinivel investigaron los efectos del consumo promedio y reciente de cannabis en la cognición global, el deterioro cognitivo global, y la independencia funcional. Los consumidores ocasionales de cannabis mostraron un mejor rendimiento cognitivo global en comparación con los no consumidores. El nivel de deterioro cognitivo y problemas funcionales no estuvieron asociado con el uso de cannabis. El consumo reciente de cannabis se vinculó con una peor cognición en las visitas del estudio cuando los participantes tenían toxicología de orina de THC positivo­esta disminución a corto plazo de la cognición se debió a una peor memoria, pero no se extendió a los informes de deterioros funcionales. El consumo ocasional (≤ semanal) de cannabis se asoció con una mejor cognición global a lo largo del tiempo en adultos mayores con VIH, un grupo susceptible a la inflamación crónica y la disfunción cognitiva. La exposición reciente al THC puede tener un impacto negativo temporal en la memoria. Los efectos de dosis específicas de cannabinoides en la cognición y sus mecanismos de acción biológicos deben ser investigados en personas mayores con el fin de informar el uso seguro y eficaz del cannabis medicinal.

Mitigating the health effects of systemic racism: Evaluation of the Race-Based Stress and Trauma Empowerment intervention.

BACKGROUND: Disparities in physical and mental health among Black, Indigenous, and People of Color (BIPOC) are well-documented and mirrored in the Veteran population. Chronic stress due to racism and discrimination is one possible mechanism driving these negative health outcomes. The Race-Based Stress and Trauma Empowerment (RBSTE) group is a novel, manualized, health promotion intervention designed to address the direct and indirect impacts of racism among Veterans of Color. This paper describes the protocol of the first pilot randomized controlled trial (RCT) of RBSTE. This study will examine the feasibility, acceptability, and appropriateness of RBSTE compared to an active control (an adaptation of Present-Centered Therapy; PCT) in a Veterans Affairs (VA) healthcare setting. A secondary aim is to identify and optimize strategies for holistic evaluation. METHODS: Veterans of Color (N = 48) endorsing perceived discrimination and stress will be randomized to RBSTE or PCT; both groups will be delivered in 8 weekly, 90-min virtual group sessions. Outcomes will include measures of psychological distress, discrimination and ethnoracial identity, holistic wellness, and allostatic load. Measures will be administered at baseline and post-intervention. CONCLUSION: This study will inform future interventions targeting identity-based stressors and represents an important step in advancing equity for BIPOC in medicine and research. CLINICAL TRIAL REGISTRATION NUMBER: NCT05422638.

Tai chi or health education for older adults with hypertension: effects on mental health and psychological resilience to COVID-19.

OBJECTIVE: To compare the effectiveness of 12 weeks of community-based, in-person, group Tai Chi (TC) and Health Education (HAP-E) in improving health and wellbeing in older adults with hypertension and in promoting psychological resilience during COVID-19. METHODS: A 12-week randomized controlled trial (RCT) in San Diego County, USA. Self-reported depressive symptoms, anxiety, sleep disturbances, gratitude, resilience, mental and physical health were assessed in-person pre- and post-intervention, and by long-term follow-up surveys during COVID-19. Linear mixed-effects models were used to assess study arm differences over time and logistic regression to identify predictors of positive intervention response. RESULTS: Of 182 randomized participants (72.6 ± 7.9 yrs; 72% female), 131 completed the intervention. Modest improvements in health and wellbeing occurred post-intervention in both arms (Cohen's d: TC = 0.38, 95% CI: 0.25-0.51; HAP-E = 0.24, 0.11-0.37), though positive intervention responses were more than twice as likely in TC (OR = 2.29, 1.07-4.57). Younger age, higher anxiety, and poorer mental health at baseline predicted greater odds of response. Small declines in health and wellbeing were reported at the first COVID-19 follow-up, with smaller declines in the TC arm (Cohen's d: TC = -0.15, -0.31-0.00; HAP-E = -0.34, -0.49 to -0.19). Health and wellbeing stabilized at the second COVID-19 follow-up. Most participants (>70%) reported that the interventions benefitted their health and wellbeing during COVID-19. CONCLUSION: TC and HAP-E improved health and wellbeing, though TC conferred greater odds of an improved mental health response. Declines in health and wellbeing were observed at pandemic follow-up, with smaller declines in the TC arm, suggesting increased resilience.

Impact of exclusive enteral nutrition on the gut microbiome of children with medical complexity.

BACKGROUND: Children with medical complexity (CMC) often require enteral tube feedings to meet their nutrition needs. Many, however, experience symptoms of feeding intolerance, such as vomiting and pain. The goal of this analysis was to examine the relationship between diet and the gut microbiome, controlling for medications, among CMC receiving enteral tube feedings, CMC consuming oral nutrition, and healthy controls. Given the variety of available commercial formula preparations, we were also interested in examining the impact of different formula types on the CMC microbiome. METHODS: Fecal samples from 91 children (57 CMC and 34 healthy controls) were collected and analyzed. Parents completed clinical and dietary questionnaires. 16S ribosomal RNA amplicon sequencing was completed using the QIIME2 pipeline. RESULTS: A significant decrease in alpha diversity among CMC receiving exclusive enteral nutrition (CMC EEN) compared with healthy controls (Shannon P = 0.006 and Faith's phylogenetic distance P = 0.006) was found that was not observed between CMC receiving oral nutrition and healthy controls. Significant differences in beta diversity were also observed between CMC EEN and healthy controls, with CMC EEN having a greater relative abundance of Enterobacteriaceae and obligate anaerobes. Differences were also noted between CMC EEN and CMC receiving oral nutrition (Aitchison distance P = 0.001); however, no differences were observed between CMC receiving oral nutrition and healthy controls. CONCLUSION: Despite similarities in medication profiles, CMC EEN have decreased alpha diversity and differences in beta diversity compared with healthy controls not observed in CMC receiving oral nutrition, highlighting the impact of diet over medications.

Deep Dive into the Long Haul: Analysis of Symptom Clusters and Risk Factors for Post-Acute Sequelae of COVID-19 to Inform Clinical Care.

Long COVID is a chronic condition characterized by symptoms such as fatigue, dyspnea, and cognitive impairment that persist or relapse months after an acute infection with the SARS-CoV-2 virus. Many distinct symptoms have been attributed to Long COVID; however, little is known about the potential clustering of these symptoms and risk factors that may predispose patients to certain clusters. In this study, an electronic survey was sent to patients in the UC San Diego Health (UCSDH) system who tested positive for COVID-19, querying if patients were experiencing symptoms consistent with Long COVID. Based on survey results, along with patient demographics reported in the electronic health record (EHR), linear and logistic regression models were used to examine putative risk factors, and exploratory factor analysis was performed to determine symptom clusters. Among 999 survey respondents, increased odds of Long COVID (n = 421; 42%) and greater Long COVID symptom burden were associated with female sex (OR = 1.73, 99% CI: 1.16-2.58; ß = 0.48, 0.22-0.75), COVID-19 hospitalization (OR = 4.51, 2.50-8.43; ß = 0.48, 0.17-0.78), and poorer pre-COVID self-rated health (OR = 0.75, 0.57-0.97; ß = -0.19, -0.32--0.07). Over one-fifth of Long COVID patients screened positive for depression and/or anxiety, the latter of which was associated with younger age (OR = 0.96, 0.94-0.99). Factor analysis of 16 self-reported symptoms suggested five symptom clusters-gastrointestinal (GI), musculoskeletal (MSK), neurocognitive (NC), airway (AW), and cardiopulmonary (CP), with older age (ß = 0.21, 0.11-0.30) and mixed race (ß = 0.27, 0.04-0.51) being associated with greater MSK symptom burden. Greater NC symptom burden was associated with increased odds of depression (OR = 5.86, 2.71-13.8) and anxiety (OR = 2.83, 1.36-6.14). These results can inform clinicians in identifying patients at increased risk for Long COVID-related medical issues, particularly neurocognitive symptoms and symptom clusters, as well as informing health systems to manage operational expectations on a population-health level.

Independent and Joint Associations of Pessimism, Total Calorie Intake and Acid-Producing Diets with Insomnia Symptoms among Breast Cancer Survivors.

Insomnia is prevalent in up to 40% of breast cancer survivors. Few studies have examined pessimism and dietary factors as risk factors for insomnia among breast cancer survivors. We leveraged a cohort of 2944 breast cancer survivors who enrolled in the Women's Healthy Eating and Living study; these survivors provided dietary, insomnia, mental health, demographic, and lifestyle information at baseline and at 1- and 4-year follow-up assessments. Insomnia symptoms were assessed using the Women's Health Initiative (WHI)-Insomnia Rating Scale, and pessimism was assessed using the Life Orientation Test Revised (LOT-R). Total calorie intake and acid-producing diets were assessed using 24 h dietary recalls. Multivariable-adjusted generalized estimating equation (GEE) models were used to test the independent and joint effects of psychological and dietary factors on insomnia. In the multivariable model, women in the third tertile of pessimism had greater odds (OR = 1.57 95% CI [1.37−1.79]) of insomnia when compared to women in the lowest tertile. Total calorie intake and acid-producing diets were each independently and significantly associated with insomnia symptoms. Further, pessimism and calorie intake/acid-producing diets were jointly associated with insomnia. For instance, women with pessimism scores in tertile 3 and total calorie intakes < median reported 2 times the odds (OR = 2.09; 95% CI [1.51−3.47]) of insomnia compared to women with pessimism score in tertile 1 and calorie intakes < median. Our results highlight the need for patient care regarding mental health, and recommendations of healthy dietary intakes for breast cancer survivors.

Salivary bacterial signatures in depression-obesity comorbidity are associated with neurotransmitters and neuroactive dipeptides.

BACKGROUND: Depression and obesity are highly prevalent, often co-occurring conditions marked by inflammation. Microbiome perturbations are implicated in obesity-inflammation-depression interrelationships, but how the microbiome mechanistically contributes to pathology remains unclear. Metabolomic investigations into microbial neuroactive metabolites may offer mechanistic insights into host-microbe interactions. Using 16S sequencing and untargeted mass spectrometry of saliva, and blood monocyte inflammation regulation assays, we identified key microbes, metabolites and host inflammation in association with depressive symptomatology, obesity, and depressive symptomatology-obesity comorbidity. RESULTS: Gram-negative bacteria with inflammation potential were enriched relative to Gram-positive bacteria in comorbid obesity-depression, supporting the inflammation-oral microbiome link in obesity-depression interrelationships. Oral microbiome was more highly predictive of depressive symptomatology-obesity co-occurrences than of obesity or depressive symptomatology independently, suggesting specific microbial signatures associated with obesity-depression co-occurrences. Mass spectrometry analysis revealed significant changes in levels of signaling molecules of microbiota, microbial or dietary derived signaling peptides and aromatic amino acids among depressive symptomatology, obesity and comorbid obesity-depression. Furthermore, integration of the microbiome and metabolomics data revealed that key oral microbes, many previously shown to have neuroactive potential, co-occurred with potential neuropeptides and biosynthetic precursors of the neurotransmitters dopamine, epinephrine and serotonin. CONCLUSIONS: Together, our findings offer novel insights into oral microbial-brain connection and potential neuroactive metabolites involved.

Systemic Inflammation and Cognitive Decrements in Patients With Stage B Heart Failure.

OBJECTIVE: This study aimed to investigate the role of systemic inflammation in reduced cognitive functioning in patients with early-stage heart failure (HF) while determining associations with other cardiovascular risk factors. METHODS: Patients with stage B HF (n = 270; mean [standard deviation] age = 66.1 [10.1] years) were examined cross-sectionally for relationships among cardiovascular disease (CVD) and psychological risk factors, C-reactive protein (CRP), and Montreal Cognitive Assessment (MoCA) scores. A subsample (n = 83) at high risk for stage C HF (B-type natriuretic peptide levels ≥65 pg/ml) were followed up for 12 months for relationships between CRP levels and cognitive function. RESULTS: Baseline smoking (χ2 = 6.33), unmarried (χ2 = 12.0), hypertension (χ2 = 5.72), greater body mass index (d = 0.45), and physical fatigue (d = 0.25) were related to higher CRP levels (p values < .05). Cross-sectionally, CRP levels were negatively related to MoCA scores, beyond CVD (ΔR2 = 0.022, ß = -0.170, p < .010) and psychological risk factors (ΔR2 = 0.016, ß = 0.145, p < .027), and related to mild cognitive impairment criteria (odds ratio = 1.35, 95% confidence interval [CI] = 1.00-1.81, p = .046). Across 12 months, B-type natriuretic peptide high-risk patients with CRP levels ≥3 mg/L had lower MoCA scores (23.6; 95% CI = 22.4-24.8) than did patients with CRP levels <3 mg/L (25.4; 95% CI = 24.4-26.5; p = .024). CONCLUSIONS: Patients with stage B HF and heightened CRP levels had greater cognitive impairment at baseline and follow-up, independent of CVD and potentially psychological risk factors. Low-grade systemic inflammation may be one mechanism involved in cognitive dysfunction at early stages of HF.

Independent and Joint Impacts of Acid-Producing Diets and Depression on Physical Health among Breast Cancer Survivors.

The purpose of this study was to examine the independent and joint associations of acid-producing diets and depressive symptoms with physical health among breast cancer survivors. We studied a cohort of 2944 early stage breast cancer survivors who provided dietary, physical health, demographic, and lifestyle information at baseline, year 1, and year 4. We assessed the intakes of acid-producing diets via two commonly used dietary acid load scores: potential renal acid load (PRAL) and net endogenous acid production (NEAP). Physical health was measured using the Rand 36-Item Short Form Health Survey (SF-36), consisting of physical functioning, role limitation due to physical function, bodily pain, general health, and overall physical health subscales. Increased dietary acid load and depression were each independently and significantly associated with reduced physical health subscales and overall physical health. Further, dietary acid load and depression were jointly associated with worse physical health. For instance, depressed women with dietary acid load higher than median reported 2.75 times the risk (odds ratio = 2.75; 95% confidence interval: 2.18-3.47) of reduced physical function and 3.10 times the risk of poor physical health (odds ratio = 3.10; 95% confidence interval: 2.53-3.80) compared to non-depressed women with dietary acid load lower than median. Our results highlight the need of controlling acid-producing diets and the access of mental care for breast cancer survivors.

Daily Cannabis Use is Associated With Lower CNS Inflammation in People With HIV.

OBJECTIVE: Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis's anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH. METHODS: 263 individuals were categorized into four groups: HIV- non-cannabis users (n = 65), HIV+ non-cannabis users (n = 105), HIV+ moderate cannabis users (n = 62), and HIV+ daily cannabis users (n = 31). Differences in pro-inflammatory biomarkers (IL-6, MCP-1/CCL2, IP-10/CXCL10, sCD14, sTNFR-II, TNF-α) by study group were determined by Kruskal-Wallis tests. Multivariable linear regressions examined relationships between biomarkers and seven cognitive domains, adjusting for age, sex/gender, race, education, and current CD4 count. RESULTS: HIV+ daily cannabis users showed lower MCP-1 and IP-10 levels in CSF compared to HIV+ non-cannabis users (p = .015; p = .039) and were similar to HIV- non-cannabis users. Plasma biomarkers showed no differences by cannabis use. Among PWH, lower CSF MCP-1 and lower CSF IP-10 were associated with better learning performance (all ps < .05). CONCLUSIONS: Current daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning which is commonly impaired in PWH. Cannabinoid-related reductions of MCP-1 and IP-10, if confirmed, suggest a role for medicinal cannabis in the mitigation of persistent inflammation and cognitive impacts of HIV.

Searching for host immune-microbiome mechanisms in obsessive-compulsive disorder: A narrative literature review and future directions.

Obsessive-compulsive disorder (OCD) is disabling and often treatment-refractory. Host immunity and gut microbiota have bidirectional communication with each other and with the brain. Perturbations to this axis have been implicated in neuropsychiatric disorders, but immune-microbiome signaling in OCD is relatively underexplored. We review support for further pursuing such investigations in OCD, including: 1) gut microbiota has been associated with OCD, but causal pathogenic mechanisms remain unclear; 2) early environmental risk factors for OCD overlap with critical periods of immune-microbiome development; 3) OCD is associated with increased risk of immune-mediated disorders and changes in immune parameters, which are separately associated with the microbiome; and 4) gut microbiome manipulations in animal models are associated with changes in immunity and some obsessive-compulsive symptoms. Theoretical pathogenic mechanisms could include microbiota programming of cytokine production, promotion of expansion and trafficking of peripheral immune cells to the CNS, and regulation of microglial function. Immune-microbiome signaling in OCD requires further exploration, and may offer novel insights into pathogenic mechanisms and potential treatment targets for this disabling disorder.

Trajectories of Depressive Symptoms, Neurocognitive Function, and Viral Suppression With Antiretroviral Therapy Among Youth With HIV Over 36 months.

BACKGROUND: Depression and neurocognitive impairment are highly prevalent among persons living with HIV and associated with poorer clinical outcomes; however, longitudinal studies of depression-neurocognition relationships in youth living with HIV (YLWH), and the role of antiretroviral therapy (ART), are lacking. This study tested whether (1) depressive symptomatology, across somatic, cognitive, and affective symptom domains, improved with ART and (2) more severe depressive symptoms at baseline were associated with poorer neurocognitive function and poorer HIV suppression. SETTING: Data were collected from 181 YLWH (18-24 years) who were treatment-naive, a subset of whom (n = 116) initiated ART. METHODS: Participants were categorized into elevated (DS) or nonelevated (non-DS) depressive symptom groups at entry (Beck Depression Inventory-II ≥14) and followed for 36 months. Neurocognition (5-domain battery) and depressive symptoms were repeatedly assessed. Longitudinal models examined depressive symptomatology, neurocognition, and odds of HIV nonsuppression by group. RESULTS: Greater improvements in depressive symptoms were observed in the DS group over 36 months [beta = -0.14, (-0.24 to -0.03)], particularly within cognitive and affective domains. Verbal learning performance increased in the DS group [beta = 0.13, (0.01 to 0.24)], whereas psychomotor function improved somewhat in the non-DS group [beta = -0.10, (-0.22 to 0.00)]. Adjusted for ART adherence, odds of HIV nonsuppression did not significantly differ by group [odds ratio = 0.22, (0.04 to 1.23)]; however, greater somatic symptoms at study entry were associated with an increased risk of nonsuppression over time [odds ratio = 2.33 (1.07 to 5.68)]. CONCLUSION: Depressive symptoms were associated with differential neurocognitive trajectories, and somatic depressive symptoms at baseline may predict poorer subsequent HIV suppression. Identifying and treating depressive symptoms at ART initiation may benefit neurocognitive and clinical outcomes in YLWH.

Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms.

The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals' lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.

Effects of Caloric Intake and Aerobic Activity in Individuals with Prehypertension and Hypertension on Levels of Inflammatory, Adhesion and Prothrombotic Biomarkers-Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Cardiopulmonary fitness and low calorie diets have been shown to reduce inflammation but few studies have been conducted in individuals with elevated blood pressure (BP) in a randomized intervention setting. Thereby, adhesion biomarkers, e.g., soluble intercellular adhesion molecule (sICAM)-3, have not been examined so far. METHODS: Sixty-eight sedentary prehypertensive and mildly hypertensive individuals (mean age ± SEM: 45 ± 1 years; mean BP: 141/84 ± 1/1 mmHg) were randomized to one of three 12-week intervention groups: cardio training and caloric reduction, cardio training alone, or wait-list control group. Plasma levels of inflammatory, adhesion and prothrombotic biomarkers were assessed. In a second step, intervention groups were combined to one sample and multivariate regression analyses were applied in order to account for exercise and diet behavior changes. RESULTS: There were no significant differences among the intervention groups. In the combined sample, greater caloric reduction was associated with a larger increase of sICAM-3 (p = 0.026) and decrease of C-reactive protein (p = 0.018) as a result of the interventions. More cardio training was associated with increases of sICAM-3 (p = 0.046) as well as interleukin-6 (p = 0.004) and a decrease of tumor necrosis factor- (p = 0.017) levels. Higher BP predicted higher plasminogen activator inhibitor (PAI)-1 (p = 0.001), and greater fitness predicted lower PAI-1 levels (p = 0.006) after the intervention. CONCLUSIONS: In prehypertensive and hypertensive patients, plasma levels of the adhesion molecule sICAM-3 and inflammatory biomarkers have different response patterns to cardio training with and without caloric reduction. Such anti-inflammatory and anti-thrombotic effects may have implications for the prevention of atherothrombotic cardiovascular disease among individuals at increased risk.