Impact of repeated blast exposure on active-duty United States Special Operations Forces.

United States (US) Special Operations Forces (SOF) are frequently exposed to explosive blasts in training and combat, but the effects of repeated blast exposure (RBE) on SOF brain health are incompletely understood. Furthermore, there is no diagnostic test to detect brain injury from RBE. As a result, SOF personnel may experience cognitive, physical, and psychological symptoms for which the cause is never identified, and they may return to training or combat during a period of brain vulnerability. In 30 active-duty US SOF, we assessed the relationship between cumulative blast exposure and cognitive performance, psychological health, physical symptoms, blood proteomics, and neuroimaging measures (Connectome structural and diffusion MRI, 7 Tesla functional MRI, [11C]PBR28 translocator protein [TSPO] positron emission tomography [PET]-MRI, and [18F]MK6240 tau PET-MRI), adjusting for age, combat exposure, and blunt head trauma. Higher blast exposure was associated with increased cortical thickness in the left rostral anterior cingulate cortex (rACC), a finding that remained significant after multiple comparison correction. In uncorrected analyses, higher blast exposure was associated with worse health-related quality of life, decreased functional connectivity in the executive control network, decreased TSPO signal in the right rACC, and increased cortical thickness in the right rACC, right insula, and right medial orbitofrontal cortex-nodes of the executive control, salience, and default mode networks. These observations suggest that the rACC may be susceptible to blast overpressure and that a multimodal, network-based diagnostic approach has the potential to detect brain injury associated with RBE in active-duty SOF.

A qualitative study exploring LGBTQ genetic counseling students' relationships with peers and faculty in graduate school.

Lesbian, gay, bisexual, transgender, queer/questioning, and other sexual and gender minority (LGBTQ) students in healthcare professional programs face discrimination in their training, leading them to hide their identities and hindering their ability to form as meaningful connections with their classmates and faculty as non-LGBTQ students. To date, no studies have been published characterizing the LGBTQ student experience in genetic counseling programs. However, other historically oppressed groups such as Black, Indigenous, and people of color (BIPOC) genetic counseling students report feelings of isolation and negative impacts on mental health due to their racial or ethnic identity. This study explored how LGBTQ identity impacted relationships between genetic counseling students and their classmates and faculty in graduate school. In this qualitative study using constructivist grounded theory, 13 LGBTQ students and recent graduates of Canadian and American accredited genetic counseling programs were interviewed via videoconferencing. Participants reported determinants in self-disclosing their LGBTQ identity to their classmates and faculty and described ways in which their LGBTQ identity impacted relationships with individuals in their training programs. In particular, many described an overall heteronormative training environment, a hesitation to disclose their identity to faculty due to the professional nature of the relationship, and a sense of isolation. Participants also described the ways in which intersecting minoritized identities impacted their experiences as an LGBTQ student. This research contributes to the minimal literature about LGBTQ genetic counseling student experiences and has implications for addressing cisheteronormative curricula and attitudes in genetic counseling programs.

Changes in social work students' attitudes and knowledge following opioid overdose prevention training.

Background: Opioid use disorders are widespread, commonly occurring, and have serious impacts on individuals, families, and communities. When adequately trained, social workers play a pivotal role in treating populations impacted by opioid use through the provision of high-quality services and the shifting of negative attitudes related to opioid use. However, workforce projections indicate a growing shortage of behavioral health professionals qualified to work with such populations and, presently, social work programs are not equipped to meet these workforce needs. Emerging evidence suggests opioid overdose education is associated with improved attitudes and knowledge among health professions; however, less information exists on the outcomes of such training among social work students. Schools of social work must develop and evaluate curricular components related to opioid use prevention and management to adequately prepare students for clinical work as social work practitioners. Methods: Thirty-three advanced-year MSW students received opioid overdose training as part of a day-long seminar on substance use. Content included acute effects of opioids, withdrawal symptoms, risk factors, signs of overdose, naloxone training, and harm reduction principles. Using a single-group pretest-posttest design, students completed the Opioid Overdose Attitudes Scale (OOAS) and the Opioid Overdose Knowledge Scale (OOKS). To evaluate students' attitudes and knowledge, investigators compared overall and subscale means before and after the training via paired samples t-tests. Results: Findings indicated statistically significant improvements in the "concerns" and "competence" domains of the OOAS. Likewise, findings indicated statistically significant improvements in the "risk," "signs," "action," and "naloxone use" domains of the OOKS. Conclusion: Students reported improved opioid overdose-related knowledge and attitudes when assessed after the training as compared to before the training. Due to the nature of the study design, causality cannot be inferred from the training outcomes. Findings may help other social work programs develop curricular components related to opioid use.

Traffic-related particulate matter affects behavior, inflammation, and neural integrity in a developmental rodent model.

Recent studies indicate that exposure to airborne particulate matter (PM) is associated with cognitive delay, depression, anxiety, autism, and neurodegenerative diseases; however, the role of PM in the etiology of these outcomes is not well-understood. Therefore, there is a need for controlled animal studies to better elucidate the causes and mechanisms by which PM impacts these health outcomes. We assessed the effects of gestational and early life exposure to traffic-related PM on social- and anxiety-related behaviors, cognition, inflammatory markers, and neural integrity in juvenile male rats. Gestating and lactating rats were exposed to PM from a Boston (MA, USA) traffic tunnel for 5 h/day, 5 days/week for 6 weeks (3 weeks gestation, 3 weeks lactation). The target exposure concentration for the fine fraction of nebulized PM, measured as PM2.5, was 200 µg/m3. To assess anxiety and cognitive function, F1 male juveniles underwent elevated platform, cricket predation, nest building, social behavior and marble burying tests at 32-60 days of age. Upon completion of behavioral testing, multiple cytokines and growth factors were measured in these animals and their brains were analyzed with diffusion tensor MRI to assess neural integrity. PM exposure had no effect on litter size or weight, or offspring growth; however, F1 litters developmentally exposed to PM exhibited significantly increased anxiety (p = 0.04), decreased cognition reflected in poorer nest-organization (p = 0.04), and decreased social play and allogrooming (p = 0.003). MRI analysis of ex vivo brains revealed decreased structural integrity of neural tissues in the anterior cingulate and hippocampus in F1 juveniles exposed to PM (p < 0.01, p = 0.03, respectively). F1 juvenile males exposed to PM also exhibited significantly decreased plasma levels of both IL-18 (p = 0.03) and VEGF (p = 0.04), and these changes were inversely correlated with anxiety-related behavior. Chronic exposure of rat dams and their offspring to traffic-related PM during gestation and lactation decreases social behavior, increases anxiety, impairs cognition, decreases levels of inflammatory and growth factors (which are correlated with behavioral changes), and disrupts neural integrity in the juvenile male offspring. Our findings add evidence that exposure to traffic-related air pollution during gestation and lactation is involved in the etiology of autism spectrum disorder and other disorders which include social and cognitive deficits and/or increased anxiety.

Optimizing screening, brief intervention, and referral to treatment (SBIRT) training for nurses and social workers: Testing the added effect of online patient simulation.

Background: Social workers and nurses are critical to the amelioration of substance misuse, making their training in evidence-based practices such as screening, brief intervention, and referral to treatment (SBIRT) particularly pertinent. Online patient simulation (OPS) is one training modality that allows students to develop and practice SBIRT skills that they might not obtain through didactic instruction, but it can be time and resource intensive. The aim of this study was to test the effect of OPS, over and above in-person training, on students' SBIRT attitudes, knowledge, and perceived skills. Methods: Social work and nursing students (N = 308) were recruited from a college in the northeastern United States. Students in the study were randomly assigned to either training as usual (TAU), which included pre-coursework videos, in-person didactic instruction, and role-plays, or the experimental condition (EXP), consisting of TAU plus access to self-paced SBIRT skills practice using OPS by SIMmersion. The SBIRT Attitudes, Self-perception of Skills, and Knowledge (AKS) survey was delivered at baseline, immediately post-training, and at 30-day follow-up (post-30) to assess overall changes as well as changes in the specific domains of SBIRT confidence, importance, and attitudes. Paired t tests were conducted to determine differences in mean scores between time points for the entire sample. Independent-samples t tests were conducted to test differences between EXP and TAU on AKS scores at each time point and to test differences between high and low OPS use. Results: Results showed a significant difference from pre- to post-training on composite AKS scores. There were no significant differences between TAU and EXP in composite scores or by AKS domain, and no differences within the EXP group for those with high and low use. Conclusions: Participants in EXP did not have significantly increased AKS scores, demonstrating that access to OPS did not produce an additive effect on the acquisition of self-perceived SBIRT knowledge, attitudes, and skills.

Impact of virtual learning on interprofessional simulation outcomes: A mixed-methods study.

Health professions education is tasked with preparing the behavioral health workforce to provide accessible, high-quality, interprofessional care to meet the needs of geographically-isolated populations. Interprofessional experiences, like simulation, are an effective pedagogical tool, yet traditionally occur in-person. It is essential to adapt simulation experiences for the virtual environment to increase training accessibility among the emerging rural workforce. This study aimed to understand the impact of the virtual learning environment on interprofessional simulation (IPS) outcomes among social work (MSW) and nursing (MSN) students. The study sample (N=127) was composed of MSW (n=48) and MSN (n=79) students at a private university in the United States. The mixed-methods study utilized 1. independent samples t-tests to examine differences in students' interprofessional teaming behaviors, measured by the Performance Assessment Communication and Teamwork (PACT), after participation in a virtual interprofessional simulation (IPS) versus a traditional, in-person IPS; and 2. independent samples t-tests and qualitative thematic analysis to explore the feasibility and acceptability of the IPS among the virtual and in-person groups via the PACT and a satisfaction survey. Both IPS featured a case contextualized to take place in an underserved, rural area. Findings indicate virtual and in-person IPS provide comparable preparation in interprofessional team functioning and performance essential to interprofessional care. Students found the IPS feasible, acceptable, and were satisfied with the experience independent of platform. Virtual IPS experiences mitigate barriers to rural workforce development. Providing training in interprofessional practice using virtual platforms stands to benefit individuals in geographically-isolated communities.

The Perceived Impact of Substance Use Education on Social Work Students' Knowledge, Attitudes, and Skills.

BACKGROUND: In 2021, the Substance Abuse and Mental Health Services Administration (SAMHSA) published a report revealing that over 46 million individuals in the United States had a substance use disorder (SUD). In the same year, a record number of drug-related overdose deaths were reported. Social workers play an important role in connecting with people who use substances and providing adequate care and treatment; yet, negative attitudes and lack of holistic knowledge about individuals who use substances create challenges in providing effective care. Social work curricula that integrates substance use content has been identified as one way to address this. METHODS: A 14-week course was introduced in one institution's Master of Social Work curriculum with the goal of providing students with a comprehensive education on SUDs. Foundational knowledge and practical skill development were covered. Seventeen trained instructors taught a total of 1204 students between May 2020 and January 2022. Quantitative and qualitative data were collected to explore changes in student's self-perceived knowledge, attitudes, and skills related to substance use. RESULTS: Among those who completed the survey (N = 553), the majority felt that the course would have a positive impact on their future work and professional development. Specifically, 96.4% reported being satisfied or very satisfied with the course overall. Among those who completed a 30-day follow-up survey (n = 69), data revealed an increase in students' self-perceived knowledge, accompanied by a shift in attitudes and positive changes in self-perceived client-centered care skills. CONCLUSIONS: Findings from this article support the development, implementation, and evaluation of evidence-based substance use content within social work curricula. This has implications for improving knowledge, attitudes, and skills among social workers who work with people who use substances.

The Influence of Brain MRI Defacing Algorithms on Brain-Age Predictions via 3D Convolutional Neural Networks.

In brain imaging research, it is becoming standard practice to remove the face from the individual's 3D structural MRI scan to ensure data privacy standards are met. Face removal - or 'defacing' - is being advocated for large, multi-site studies where data is transferred across geographically diverse sites. Several methods have been developed to limit the loss of important brain data by accurately and precisely removing non-brain facial tissue. At the same time, deep learning methods such as convolutional neural networks (CNNs) are increasingly being used in medical imaging research for diagnostic classification and prognosis in neurological diseases. These neural networks train predictive models based on patterns in large numbers of images. Because of this, defacing scans could remove informative data. Here, we evaluated 4 popular defacing methods to identify the effects of defacing on 'brain age' prediction - a common benchmarking task of predicting a subject's chronological age from their 3D T1-weighted brain MRI. We compared brain-age calculations using defaced MRIs to those that were directly brain extracted, and those with both brain and face. Significant differences were present when comparing average per-subject error rates between algorithms in both the defaced brain data and the extracted facial tissue. Results also indicated brain age accuracy depends on defacing and the choice of algorithm. In a secondary analysis, we also examined how well comparable CNNs could predict chronological age from the facial region only (the extracted portion of the defaced image), as well as visualize areas of importance in facial tissue for predictive tasks using CNNs. We obtained better performance in age prediction when using the extracted face portion alone than images of the brain, suggesting the need for caution when defacing methods are used in medical image analysis.

The Influence of Brain MRI Defacing Algorithms on Brain-Age Predictions via 3D Convolutional Neural Networks.

In brain imaging research, it is becoming standard practice to remove the face from the individual's 3D structural MRI scan to ensure data privacy standards are met. Face removal - or 'defacing' - is being advocated for large, multi-site studies where data is transferred across geographically diverse sites. Several methods have been developed to limit the loss of important brain data by accurately and precisely removing non-brain facial tissue. At the same time, deep learning methods such as convolutional neural networks (CNNs) are increasingly being used in medical imaging research for diagnostic classification and prognosis in neurological diseases. These neural networks train predictive models based on patterns in large numbers of images. Because of this, defacing scans could remove informative data. Here, we evaluated 4 popular defacing methods to identify the effects of defacing on 'brain age' prediction - a common benchmarking task of predicting a subject's chronological age from their 3D T1-weighted brain MRI. We compared brain-age calculations using defaced MRIs to those that were directly brain extracted, and those with both brain and face. Significant differences were present when comparing average per-subject error rates between algorithms in both the defaced brain data and the extracted facial tissue. Results also indicated brain age accuracy depends on defacing and the choice of algorithm. In a secondary analysis, we also examined how well comparable CNNs could predict chronological age from the facial region only (the extracted portion of the defaced image), as well as visualize areas of importance in facial tissue for predictive tasks using CNNs. We obtained better performance in age prediction when using the extracted face portion alone than images of the brain, suggesting the need for caution when defacing methods are used in medical image analysis.

Optimizing Brain Health of United States Special Operations Forces.

United States Special Operations Forces (SOF) personnel are frequently exposed to explosive blasts in training and combat. However, the effects of repeated blast exposure on the human brain are incompletely understood. Moreover, there is currently no diagnostic test to detect repeated blast brain injury (rBBI). In this "Human Performance Optimization" article, we discuss how the development and implementation of a reliable diagnostic test for rBBI has the potential to promote SOF brain health, combat readiness, and quality of life.

Interprofessional skills as a predictor of culturally congruent practice behaviors.

INTRODUCTION: Evidence suggests that the development and implementation of interprofessional skills can positively impact culturally congruent practice among providers and patients, improving access and quality of care. Exploring the relationship between interprofessional skills and culturally congruent practice within health profession education can inform curricular efforts that better prepare the emerging workforce to provide accessible, high-quality care. METHOD: This study examined if interprofessional skills predict culturally congruent practice behaviors in an interprofessional health care simulation with Master of Social Work and Master of Science in Nursing students (N = 79). Simple linear regressions were conducted to evaluate whether interprofessional skills, across five domains (team structure, leadership, situation monitoring, mutual support, and communication) in the Performance Assessment Communication and Teamwork, significantly predicted culturally congruent practice behaviors, overall and across three subscales (culturally specific care; cultural assessment; and culturally sensitive and professionally appropriate attitudes, values, and beliefs), in the Cultural Competence Clinical Evaluation Tool-Student Version. RESULTS: Among the sample, the interprofessional skill domains of leadership, situation monitoring, and communication predicted culturally congruent practice behaviors overall. Additionally, results indicated that communication predicted culturally specific care; team structure, leadership, situation monitoring, mutual support, and communication predicted cultural assessment; and communication, situation monitoring, and leadership predicted culturally sensitive and professionally appropriate attitudes, values, and beliefs. DISCUSSION: Opportunities to learn and practice interprofessional skills within health profession curricula may predict Master of Social Work and Master of Science in Nursing students' culturally congruent practice behaviors; implications and limitations are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Effects of the Mindfulness-Based Blood Pressure Reduction (MB-BP) program on depression and neural structural connectivity.

BACKGROUND: Hypertension-related illnesses are a leading cause of disability and death in the United States, where hypertension prevalence in adults is 46%, with only half of those afflicted having it under control. Due to the significant challenges in long-term efficacy and adverse effects associated with pharmacological interventions, there is an eminent need for complimentary approaches for treating hypertension. Although initial studies of the Mindfulness-Based Blood Pressure Reduction program (MB-BP) indicate that this novel 8-week intervention is effective at inducing lasting decreases in blood pressure, the neural correlates are unknown. METHODS: The objectives of this study were to identify structural neural correlates of MB-BP using diffusion tensor magnetic resonance imaging (DTI) and assess potential correlations with key clinical outcomes. RESULTS: In a subset of participants (14 MB-BP, 22 controls) from a larger stage IIa randomized controlled trial, MB-BP participants exhibited increased interoception and decreased depressive symptoms compared to controls. Analyses of DTI data revealed significant group differences in multiple white matter neural tracts associated with the limbic system and/or blood pressure. Specific changes in neural structural connectivity were significantly associated with measures of interoception and depression. LIMITATIONS: Limitations include small sample size (leading to insufficient power in the analysis of blood pressure) and the study duration (3 months). The main MRI limitation is suboptimal resolution in areas of extensive neural tract crossings. CONCLUSIONS: It is concluded that MB-BP induces alterations in brain structural connectivity which could mediate beneficial changes in depression and interoceptive awareness in individuals with hypertension.

Long-Term Effects of Repeated Blast Exposure in United States Special Operations Forces Personnel: A Pilot Study Protocol.

Emerging evidence suggests that repeated blast exposure (RBE) is associated with brain injury in military personnel. United States (U.S.) Special Operations Forces (SOF) personnel experience high rates of blast exposure during training and combat, but the effects of low-level RBE on brain structure and function in SOF have not been comprehensively characterized. Further, the pathophysiological link between RBE-related brain injuries and cognitive, behavioral, and physical symptoms has not been fully elucidated. We present a protocol for an observational pilot study, Long-Term Effects of Repeated Blast Exposure in U.S. SOF Personnel (ReBlast). In this exploratory study, 30 active-duty SOF personnel with RBE will participate in a comprehensive evaluation of: 1) brain network structure and function using Connectome magnetic resonance imaging (MRI) and 7 Tesla MRI; 2) neuroinflammation and tau deposition using positron emission tomography; 3) blood proteomics and metabolomics; 4) behavioral and physical symptoms using self-report measures; and 5) cognition using a battery of conventional and digitized assessments designed to detect subtle deficits in otherwise high-performing individuals. We will identify clinical, neuroimaging, and blood-based phenotypes that are associated with level of RBE, as measured by the Generalized Blast Exposure Value. Candidate biomarkers of RBE-related brain injury will inform the design of a subsequent study that will test a diagnostic assessment battery for detecting RBE-related brain injury. Ultimately, we anticipate that the ReBlast study will facilitate the development of interventions to optimize the brain health, quality of life, and battle readiness of U.S. SOF personnel.

Altered neural networks and cognition in a hereditary colon cancer.

Familial Adenomatous Polyposis (FAP) is an autosomal dominant disorder caused by mutation of the APC gene presenting with numerous colorectal adenomatous polyps and a near 100% risk of colon cancer. Preliminary research findings from our group indicate that FAP patients experience significant deficits across many cognitive domains. In the current study, fMRI brain metrics in a FAP population and matched controls were used to further the mechanistic understanding of reported cognitive deficits. This research identified and characterized any possible differences in resting brain networks and associations between neural network changes and cognition from 34 participants (18 FAP patients, 16 healthy controls). Functional connectivity analysis was performed using FSL with independent component analysis (ICA) to identify functional networks. Significant differences between cases and controls were observed in 8 well-established resting state networks. With the addition of an aggregate cognitive measure as a covariate, these differences were virtually non-existent, indicating a strong correlation between cognition and brain activity at the network level. The data indicate robust and pervasive effects on functional neural network activity among FAP patients and these effects are likely involved in cognitive deficits associated with this disease.

Biopsychosocial correlates of psychological distress in Latina mothers.

BACKGROUND: Few studies have explored the relationship between psychological, psychosocial and biological factors among Latinas. An integrated understanding of how these factors associate with psychological distress is necessary for the development of culturally relevant screening tools and interventions. The study aim was to examine the relationships among (a) psychological distress symptoms, (b) psychosocial factors (discrimination, acculturation, acculturative stress, economic hardship), and (c) biological (DNA methylation of stress-related genes) factors among Latinas during pregnancy and postpartum period. METHODS: A sample of 150 pregnant Latinas completed the Inventory of Depression and Anxiety Symptoms II (IDAS-II), psychosocial questionnaires (discrimination, acculturation, acculturative stress, economic hardship) before (24-32 weeks) and after gestation (4-6 weeks postpartum). Blood samples were collected between 24-32 weeks gestation. Correlations were determined between psychosocial and biological measures and psychological distress measures. Multivariable linear regression models were conducted to assess the relationships between IDAS and stressors. RESULTS: Several correlations among psychosocial measures,DNA methylation factors and IDAS-II variables were identified. Among the psychosocial measures, everyday discrimination was the most strongly and consistently associated with IDAS-II. DNA methylation of NR3C1 affects the associations between psychological and psychosocial distress. LIMITATIONS: We only assessed DNA methylation during pregnancy and focused on four HPA-related genes. Longitudinal assessment of DNA methylation and genome-wide analysis can provide a better picture of the role of methylation in psychological distress. CONCLUSIONS: This work may assist clinicians and policy makers in effectively recognizing and preventing maternal mental health disparities based on discrimination and other psychosocial stressors in at-risk groups.

Keeping weight off: Mindfulness-Based Stress Reduction alters amygdala functional connectivity during weight loss maintenance in a randomized control trial.

Obesity is associated with significant comorbidities and financial costs. While behavioral interventions produce clinically meaningful weight loss, weight loss maintenance is challenging. The objective was to improve understanding of the neural and psychological mechanisms modified by mindfulness that may predict clinical outcomes. Individuals who intentionally recently lost weight were randomized to Mindfulness-Based Stress Reduction (MBSR) or a control healthy living course. Anthropometric and psychological factors were measured at baseline, 8 weeks and 6 months. Functional connectivity (FC) analysis was performed at baseline and 8 weeks to examine FC changes between regions of interest selected a priori, and independent components identified by independent component analysis. The association of pre-post FC changes with 6-month weight and psychometric outcomes was then analyzed. Significant group x time interaction was found for FC between the amygdala and ventromedial prefrontal cortex, such that FC increased in the MBSR group and decreased in controls. Non-significant changes in weight were observed at 6 months, where the mindfulness group maintained their weight while the controls showed a weight increase of 3.4% in BMI. Change in FC at 8-weeks between ventromedial prefrontal cortex and several ROIs was associated with change in depression symptoms but not weight at 6 months. This pilot study provides preliminary evidence of neural mechanisms that may be involved in MBSR's impact on weight loss maintenance that may be useful for designing future clinical trials and mechanistic studies.

Pregnancy associated epigenetic markers of inflammation predict depression and anxiety symptoms in response to discrimination.

Latina mothers, who have one of the highest fertility rates among ethnic groups in the United States (US), often experience discrimination. Psychosocial influences during pregnancy, such as discrimination stress, promotes inflammation. However, the role of epigenetic markers of inflammation as a mediator between, and predictor of, maternal discrimination stress and neuropsychiatric outcomes has not been extensively studied. The current study investigates the role of DNA methylation at FOXP3 Treg-cell-specific demethylated region (TSDR), as a marker of regulatory T (Treg) cells that are important negative regulators of inflammation, and the promoter of tumour necrosis factor-alpha (TNF-α) gene, an important pro-inflammatory cytokine, in relation to discrimination stress during pregnancy and depression and anxiety symptomatology. A sample of 148 Latina women residing in the US (mean age 27.6 years) were assessed prenatally at 24-32 weeks' gestation and 4-6 weeks postnatally for perceived discrimination exposure (Everyday Discrimination Scale, EDS), emotional distress (depression, anxiety, perinatal-specific depression), acculturation, and acculturative stress. DNA methylation levels at the FOXP3 and TNFα promoter regions from blood samples collected at the prenatal stage were assessed by bisulphite pyrosequencing. Regression analyses showed that prenatal EDS associated with postnatal emotional distress, depression and anxiety symptoms only in those individuals with higher than mean levels of FOXP3 TSDR and TNFα promoter methylation; no such significant associations were found in those with lower than mean levels of methylation for either. We further found that these relationships were mediated by TNFα only in those with high FOXP3 TSDR methylation, implying that immunosuppression via TNFα promoter methylation buffers the impact of discrimination stress on postpartum symptomatology. These results indicate that epigenetic markers of immunosuppression and inflammation play an important role in resilience or sensitivity, respectively, to prenatal stress.

Robustness of sex-differences in functional connectivity over time in middle-aged marmosets.

Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understanding of the neural mechanisms of neurocognitive aging in our own species. In the present study, we used resting state functional connectivity (rsFC) to investigate the relationship between prefrontal cortical and striatal neural interactions, and cognitive flexibility, in unanaesthetized common marmosets (Callithrix jacchus) at two time points during late middle age (8 months apart, similar to a span of 5-6 years in humans). Based on our previous findings, we also determine the reproducibility of connectivity measures over the course of 8 months, particularly previously observed sex differences in rsFC. Male marmosets exhibited remarkably similar patterns of stronger functional connectivity relative to females and greater cognitive flexibility between the two imaging time points. Network analysis revealed that the consistent sex differences in connectivity and related cognitive associations were characterized by greater node strength and/or degree values in several prefrontal, premotor and temporal regions, as well as stronger intra PFC connectivity, in males compared to females. The current study supports the existence of robust sex differences in prefrontal and striatal resting state networks that may contribute to differences in cognitive function and offers insight on the neural systems that may be compromised in cognitive aging and age-related conditions such as mild cognitive impairment and Alzheimer's disease.

Altered Resting State Brain Networks and Cognition in Familial Adenomatous Polyposis.

Familial Adenomatous Polyposis (FAP) is an autosomal dominant disorder caused by mutation of the APC gene presenting with numerous colorectal adenomatous polyps and a near 100% risk of colon cancer. Preliminary research findings from our group indicate that FAP patients experience significant deficits across many cognitive domains. In the current study, fMRI brain metrics in a FAP population and matched controls were used to further the mechanistic understanding of reported cognitive deficits. This research identified and characterized any possible differences in resting brain networks and associations between neural network changes and cognition from 34 participants (18 FAP patients, 16 healthy controls). Functional connectivity analysis was performed using FSL with independent component analysis (ICA) to identify functional networks. Significant differences between cases and controls were observed in 8 well-established resting state networks. With the addition of an aggregate cognitive measure as a covariate, these differences were virtually non-existent, indicating a strong correlation between cognition and brain activity at the network level. The data indicate robust and pervasive effects on functional neural network activity among FAP patients and these effects are likely involved in cognitive deficits associated with this disease.