Predictive modeling of response to repetitive transcranial magnetic stimulation in treatment-resistant depression.

Identifying predictors of treatment response to repetitive transcranial magnetic stimulation (rTMS) remain elusive in treatment-resistant depression (TRD). Leveraging electronic medical records (EMR), this retrospective cohort study applied supervised machine learning (ML) to sociodemographic, clinical, and treatment-related data to predict depressive symptom response (>50% reduction on PHQ-9) and remission (PHQ-9 < 5) following rTMS in 232 patients with TRD (mean age: 54.5, 63.4% women) treated at the University of California, San Diego Interventional Psychiatry Program between 2017 and 2023. ML models were internally validated using nested cross-validation and Shapley values were calculated to quantify contributions of each feature to response prediction. The best-fit models proved reasonably accurate at discriminating treatment responders (Area under the curve (AUC): 0.689 [0.638, 0.740], p < 0.01) and remitters (AUC 0.745 [0.692, 0.797], p < 0.01), though only the response model was well-calibrated. Both models were associated with significant net benefits, indicating their potential utility for clinical decision-making. Shapley values revealed that patients with comorbid anxiety, obesity, concurrent psychiatric medication use, and more chronic TRD were less likely to respond or remit following rTMS. Patients with trauma and former tobacco users were more likely to respond. Furthermore, delivery of intermittent theta burst stimulation and more rTMS sessions were associated with superior outcomes. These findings highlight the potential of ML-guided techniques to guide clinical decision-making for rTMS treatment in patients with TRD to optimize therapeutic outcomes.

Strength, speed, and anthropometric predictors of in-game batting performance in baseball.

A key focus of sports science research is the identification of quantitative assessments that can predict players' on-field performance and developmental potential. Despite efforts to establish predictive models, there are few validated measures that show reliable associations and large gaps in understanding. Here, we test a multidimensional battery of assessments developed through the USA Baseball, Prospect Development Pipeline that capture strength and functional movement abilities, and anthropometric characteristics, in a two-year cohort of collegiate baseball players from the Appalachian League. Swing propensity metrics for Zone Contact Percentage (ZCP: proportion pitches in strike zone swung at and hit) and Hard-Hit Percentage (HHP: proportion in-play balls with exit velocity ≥ 95 mph) were calculated on 189 players. Models testing hierarchical combinations of anthropometric and anthropometric plus assessment data were implemented using nested cross-validation with random forest and elastic net regression. Results indicate that anthropometric features account for 29% of variance in ZCP and 50-55% of HHP, while the addition of assessment contributed an additional 1-3% to ZCP and 5-12% to HHP, with top predictors coming from PDP strength and power assessments. These findings delineate contributions of andromorphic and physical abilities to in-game baseball performance using a validated assessment battery and advanced game statistics.

Acculturation and clinical symptoms of schizophrenia among Latine adults in the United States.

BACKGROUND: Research on acculturation and schizophrenia spectrum disorders has yielded inconsistent findings. This study aimed to clarify the influence of acculturation on symptomatology in Latine individuals with schizophrenia in the United States. METHODS: The analysis involved cross-sectional data from Latine (n = 120) and non-Latine White (n = 60) adults with schizophrenia in San Diego, California. Participants completed the Short Acculturation Scale for Hispanics (SASH), Positive and Negative Symptom Scale, and Hamilton Depression Rating Scale in their preferred language. Univariate linear regressions were implemented to identify proxy measures as predictors of acculturation scores. Analyses of variance were conducted to analyze the relationship of SASH scores and proxy measures of acculturation to symptom severity. RESULTS: Latine participants presented more symptom severity than non-Latine Whites. When categorized by acculturation status (Spanish-preferring, bicultural, and English-preferring), Spanish-preferring participants presented similar psychiatric symptoms to the non-Latine group and less severe symptoms than both other Latine groups. Analyses identified study language as the strongest proxy measure for the SASH. Latine participants assessed in English had significantly worse positive and depressive symptoms than those assessed in Spanish. Nativity status moderated the relationship between study language and symptomatology. CONCLUSIONS: Findings support an association between acculturation and symptom severity among Latine individuals with schizophrenia. The use of proxy measures of acculturation may be useful in settings where time is constrained. Future research should continue to explore acculturation and symptomatology in Latine communities.

Predictors of batting and pitching performance in the USA baseball prospect development pipeline.

This study examined the relationship between psychomotor abilities and baseball performance by analysing data from 379 athletes who participated in the USA Baseball, Prospect Development Pipeline (PDP). Hit and pitch metrics were generated during practice sessions using the RapsodoTM System. Data were compared through exploratory factor analysis and hierarchical regression. Factor analysis grouped batter's PDP evaluations into four latent variables accounting for 63% of variance. Pitcher performance grouped into three factors accounting for 51% of variance. Regression on batter data revealed a significant demographic/anthropometric base model with height, weight, and age that accounted for 58% of the batted ball speed (R2 = 0.581). Player position explained 2% of the variance (R2 = 0.604), and PDP evaluation scores contributed an additional 3% (R2 = 0.631). Regression of pitcher data showed a significant base demographic/anthropometric model accounting for 36% of fastball pitch speeds (R2 = 0.363), with the PDP evaluation scores adding 6% additional variance (R2 = 0.424). Uniformly, assessments of lower body strength added the greatest predictive information. Hand grip strength did not correlate with pitch metrics. While demographics/anthropometrics are major contributors to batted and pitched ball speed, position and psychomotor variables add statistically significant contributions and may be of practical value for player selection.

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.

Perceived discrimination and nativity status: risk of cognitive impairment among Latin American older adults.

OBJECTIVES: We examined the association between perceived discrimination and the risk of cognitive impairment with no dementia (CIND) and Alzheimer's disease and related dementias (ADRD) while considering the potential effects of nativity status. DESIGN: A prospective analysis of discrimination and nativity status with dementia and cognitive impairment was conducted among Latinx adults aged 51 years and older who participated in the Health and Retirement Study. SETTING: A national representative sample. PARTICIPANTS: A sample of 1,175 Latinx adults aged 51 years and older. MEASUREMENTS: Demographics, cognitive functioning, perceived discrimination, and nativity status (US-born vs. non-US born) were assessed. Traditional survival analysis methods (Fine and gray models) were used to account for the semi-competing risk of death with up to 10 years of follow-up. RESULTS: According to our results, neither everyday discrimination nor nativity status on their own had a statistically significant association with CIND/ADRD; however, non-US-born Latinx adults who reported no discrimination had a 42% lower risk of CIND/ADRD (SHR = 0.58 [0.41, 0.83], p = .003) than US-born adults. CONCLUSIONS: These results highlight the need for healthcare providers to assess for discrimination and provide support and resources for those experiencing discrimination. It also highlights the need for better policies that address discrimination and reduce health disparities.

Magnetic seizure therapy and electroconvulsive therapy increase aperiodic activity.

Major depressive disorder (MDD) is a leading cause of disability worldwide. One of the most efficacious treatments for treatment-resistant MDD is electroconvulsive therapy (ECT). Recently, magnetic seizure therapy (MST) was developed as an alternative to ECT due to its more favorable side effect profile. While these approaches have been very successful clinically, the neural mechanisms underlying their therapeutic effects are unknown. For example, clinical "slowing" of the electroencephalogram beginning in the postictal state and extending days to weeks post-treatment has been observed in both treatment modalities. However, a recent longitudinal study of a small cohort of ECT patients revealed that, rather than delta oscillations, clinical slowing was better explained by increases in aperiodic activity, an emerging EEG signal linked to neural inhibition. Here we investigate the role of aperiodic activity in a cohort of patients who received ECT and a cohort of patients who received MST treatment. We find that aperiodic neural activity increases significantly in patients receiving either ECT or MST. Although not directly related to clinical efficacy in this dataset, increased aperiodic activity is linked to greater amounts of neural inhibition, which is suggestive of a potential shared neural mechanism of action across ECT and MST.

Predictive Biomarkers of Treatment Response in Major Depressive Disorder.

Major depressive disorder (MDD) is a highly prevalent, debilitating disorder with a high rate of treatment resistance. One strategy to improve treatment outcomes is to identify patient-specific, pre-intervention factors that can predict treatment success. Neurophysiological measures such as electroencephalography (EEG), which measures the brain's electrical activity from sensors on the scalp, offer one promising approach for predicting treatment response for psychiatric illnesses, including MDD. In this study, a secondary data analysis was conducted on the publicly available Two Decades Brainclinics Research Archive for Insights in Neurophysiology (TDBRAIN) database. Logistic regression modeling was used to predict treatment response, defined as at least a 50% improvement on the Beck's Depression Inventory, in 119 MDD patients receiving repetitive transcranial magnetic stimulation (rTMS). The results show that both age and baseline symptom severity were significant predictors of rTMS treatment response, with older individuals and more severe depression scores associated with decreased odds of a positive treatment response. EEG measures contributed predictive power to these models; however, these improvements in outcome predictability only trended towards statistical significance. These findings provide confirmation of previous demographic and clinical predictors, while pointing to EEG metrics that may provide predictive information in future studies.

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.

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.

Differences in Social Determinants of Health Underlie Racial/Ethnic Disparities in Psychological Health and Well-Being: Study of 11,143 Older Adults.

OBJECTIVE: The authors sought to determine the impact of selected social determinants of health (SDoH) on psychological health and well-being (defined as depression, cognition, and self-rated health) among Black and Hispanic/Latinx adults relative to White adults 51-89 years of age. METHODS: Disparities in depressive symptomatology, cognition, and self-rated health were measured among 2,306 non-Hispanic/Latinx Black, 1,593 Hispanic/Latinx, and 7,244 non-Hispanic/Latinx White adults who participated in the Health and Retirement Study (N=11,143). Blinder-Oaxaca decomposition was used to examine whether differences in selected SDoH explained a larger share of the disparities than age, sex, measures of health, health behaviors, and health care utilization. Selected SDoH included education, parental education, number of years worked, marital status, veteran status, geographic residence, nativity status, income, and insurance coverage. RESULTS: Black and Hispanic/Latinx adults reported worse depressive symptomatology, cognition, and self-rated health than White adults. Selected SDoH were associated with a larger proportion of the Black-White disparities in depressive symptomatology (51%), cognition (39%), and self-rated health (37%) than were age, sex, measures of health, health behaviors, and health care utilization. SDoH were associated with a larger proportion of the Hispanic/Latinx-White disparity in cognition (76%) and self-rated health (75%), but age and physical health correlated with the disparity in depressive symptomatology (28%). Education, parental education, years worked, income, and insurance parity were SDoH associated with these disparities. CONCLUSIONS: Differences in SDoH underlie racial/ethnic disparities in depression, cognition, and self-rated health among older adults. Education, income, number of years worked, and insurance parity are key SDoH.

Magnetic seizure therapy and electroconvulsive therapy increase aperiodic activity.

Major depressive disorder (MDD) is a leading cause of disability worldwide. One of the most efficacious treatments for treatment-resistant MDD is electroconvulsive therapy (ECT). Recently, magnetic seizure therapy (MST) was developed as an alternative to ECT due to its more favorable side effect profile. While these approaches have been very successful clinically, the neural mechanisms underlying their therapeutic effects are unknown. For example, clinical "slowing" of the electroencephalogram beginning in the postictal state and extending days to weeks post-treatment has been observed in both treatment modalities. However, a recent longitudinal study of a small cohort of ECT patients revealed that, rather than delta oscillations, clinical slowing was better explained by increases in aperiodic activity, an emerging EEG signal linked to neural inhibition. Here we investigate the role of aperiodic activity in a cohort of patients who received ECT and a cohort of patients who received MST treatment. We find that aperiodic neural activity increases significantly in patients receiving either ECT or MST. Although not directly related to clinical efficacy in this dataset, increased aperiodic activity is linked to greater amounts of neural inhibition, which is suggestive of a potential shared neural mechanism of action across ECT and MST.

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.

Trends, heterogeneity, and correlates of mental health and psychosocial well-being in later-life: study of 590 community-dwelling adults aged 40-104 years.

OBJECTIVE: The goal of this study was to examine if mental health and psychosocial well-being differed between middle-aged (MA; 40-59 years), younger-old (YO; 60-79 years), and older-old (OO; 80+ years) adults with respect to their trends, heterogeneity, and correlates. METHODS: Eighteen mental health and psychosocial well-being instruments were administered to 590 adults over age 40. Cross-sectional data also included self-report-based measures of sociodemographics, cognitive functioning, physical health and activity, and body mass index. RESULTS: Age trends across instruments varied in magnitude and shape, but generally supported an inverted U-shaped trend in mental health and psychosocial well-being, with small increases from MA to YO age (d = 0.29) and smaller declines from YO to OO age (d = -0.17). A U-shaped association between age and mental health heterogeneity was also observed. The strongest correlates of mental health and psychosocial well-being differed by age (MA: perceived stress; YO: successful aging; OO: compassion toward others), as did the associations of a flourishing versus languishing mental health and well-being profile. CONCLUSIONS: Our findings support the "paradox of aging," whereby declines in physical and cognitive health co-occur with relatively preserved mental health and well-being. Our findings indicate that variance in mental and psychosocial health does not increase linearly with age and support careful consideration of heterogeneity in mental health and aging research. Our findings also suggest that mental health and psychosocial well-being decouple from stress-related dimensions in MA and become increasingly associated with positive, other-oriented emotions in OO, broadly supporting socioemotional theories of aging.

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.

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.

Primate innate immune responses to bacterial and viral pathogens reveals an evolutionary trade-off between strength and specificity.

Despite their close genetic relatedness, apes and African and Asian monkeys (AAMs) differ in their susceptibility to severe bacterial and viral infections that are important causes of human disease. Such differences between humans and other primates are thought to be a result, at least in part, of interspecies differences in immune response to infection. However, because of the lack of comparative functional data across species, it remains unclear in what ways the immune systems of humans and other primates differ. Here, we report the whole-genome transcriptomic responses of ape species (human and chimpanzee) and AAMs (rhesus macaque and baboon) to bacterial and viral stimulation. We find stark differences in the responsiveness of these groups, with apes mounting a markedly stronger early transcriptional response to both viral and bacterial stimulation, altering the transcription of ∼40% more genes than AAMs. Additionally, we find that genes involved in the regulation of inflammatory and interferon responses show the most divergent early transcriptional responses across primates and that this divergence is attenuated over time. Finally, we find that relative to AAMs, apes engage a much less specific immune response to different classes of pathogens during the early hours of infection, up-regulating genes typical of anti-viral and anti-bacterial responses regardless of the nature of the stimulus. Overall, these findings suggest apes exhibit increased sensitivity to bacterial and viral immune stimulation, activating a broader array of defense molecules that may be beneficial for early pathogen killing at the potential cost of increased energy expenditure and tissue damage.

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.