Association of psychiatric disorders with clinical diagnosis of long COVID in US veterans.

BACKGROUND: Psychiatric disorders may be a risk factor for long COVID, broadly defined as COVID-19 conditions continuing three months post-acute infection. In US Veterans with high psychiatric burden, we examined associations between psychiatric disorders and clinical diagnosis of long COVID. METHODS: We conducted a retrospective cohort study using health records from VA patients with a positive SARS-CoV-2 test from February 2020 to February 2023. Generalized linear models estimated associations between any psychiatric disorder and likelihood of subsequent diagnosis with long COVID (i.e. two or more long COVID clinical codes). Models were adjusted for socio-demographic, medical, and behavioral factors. Secondary models examined individual psychiatric disorders and age-stratified associations. RESULTS: Among 660 217 VA patients with positive SARS-CoV-2 tests, 56.3% had at least one psychiatric disorder diagnosis and 1.4% were diagnosed with long COVID. Individuals with any psychiatric disorder had higher risk for long COVID diagnosis in models adjusted for socio-demographic factors, vaccination status, smoking, and medical comorbidities (relative risk, RR = 1.28, 95% CI 1.21-1.35), with the strongest associations in younger individuals. Considering specific disorders, depressive, anxiety, and stress-related disorders were associated with increased risk for long COVID diagnoses (RRs = 1.36-1.48), but associations were in the opposite direction for substance use and psychotic disorders (RRs = 0.78-0.88). CONCLUSIONS: Psychiatric disorder diagnoses were associated with increased long COVID diagnosis risk in VA patients, with the strongest associations observed in younger individuals. Improved surveillance, treatment, and prevention for COVID-19 and its long-term sequelae should be considered for individuals with psychiatric conditions.

Psychological Resilience to Trauma and Risk of COVID-19 Infection and Somatic Symptoms Across 2 Years.

OBJECTIVE: Exposure to trauma increases the risk of somatic symptoms, as well as acute and chronic physical diseases. However, many individuals display psychological resilience, showing positive psychological adaptation despite trauma exposure. Resilience to prior trauma may be a protective factor for physical health during subsequent stressors, including the COVID-19 pandemic. METHODS: Using data from 528 US adults in a longitudinal cohort study, we examined psychological resilience to lifetime potentially traumatic events early in the pandemic and the risk of COVID-19 infection and somatic symptoms across 2 years of follow-up. Resilience was defined as level of psychological functioning relative to lifetime trauma burden, assessed in August 2020. Outcomes included COVID-19 infection and symptom severity, long COVID, and somatic symptoms assessed every 6 months for 24 months. Using regression models, we examined associations between resilience and each outcome adjusting for covariates. RESULTS: Higher psychological resilience to trauma was associated with a lower likelihood of COVID-19 infection over time, with one standard deviation higher resilience score associated with a 31% lower likelihood of COVID-19 infection, adjusting for sociodemographics and vaccination status. Furthermore, higher resilience was associated with lower levels of somatic symptoms during the pandemic, adjusting for COVID-19 infection and long COVID status. In contrast, resilience was not associated with COVID-19 disease severity or long COVID. CONCLUSIONS: Psychological resilience to prior trauma is associated with lower risk of COVID-19 infection and lower somatic symptoms during the pandemic. Promoting psychological resilience to trauma may benefit not only mental but also physical health.

Post-traumatic stress disorder and risk for hospitalization and death following COVID-19 infection.

Post-traumatic stress disorder (PTSD) is associated with an increased risk for physical illnesses and early mortality. However, we do not know if it also increases the risk for adverse outcomes of coronavirus disease 2019 (COVID-19). In this retrospective cohort study, we examined associations of PTSD and other psychiatric disorders with risk for hospitalization and death in the 60 days following a COVID-19 infection in 228,367 U.S. Department of Veteran Affairs (VA) patients who tested positive for COVID-19 between February 2020 and August 2021 (age m = 60.6, 89.5% male). Generalized linear models estimated associations of PTSD and other psychiatric disorders with outcomes following a positive SARS-CoV-2 test, adjusting for socio-demographic, medical, and behavioral factors. Among 228,367 VA patients, 25.6% had PTSD, and 28.2% had a psychiatric disorder other than PTSD. In the 60 days following a positive COVID-19 test, 15% of patients were hospitalized, and 6% died. Patients with PTSD had an increased risk for both hospitalization (adjusted relative risk, ARR = 1.18, 95% CI 1.15-1.21) and death (ARR = 1.13, 95% CI 1.08-1.19) relative to those with no psychiatric disorders, adjusting for socio-demographics. Estimates remained significant when models were additionally adjusted for medical comorbidities and smoking. Patients with other psychiatric disorders also had an increased risk of adverse COVID-19 outcomes, with larger effect sizes than PTSD in older (≥65 years) but not younger patients. In this large-scale study of VA patients, individuals with PTSD, and other psychiatric disorders, had heightened vulnerability to severe adverse outcomes of COVID-19; thus, individuals with PTSD should also be considered at higher risk for severe COVID-19 outcomes, and potentially prioritized for vaccination, screening, and early treatment intervention for COVID-19.

Adverse and traumatic exposures, posttraumatic stress disorder, telomere length, and hair cortisol - Exploring associations in a high-risk sample of young adult residential care leavers.

Background: Childhood adversities (CAs), potentially traumatic exposures (PTEs), and posttraumatic stress disorder (PTSD) are known to increase the risk for poor health outcomes, including diseases of aging and early mortality. Telomere length (TL) and hair cortisol concentrations (HCC) are biomarkers known to be associated with CA and PTEs, and PTSD, but there is considerable heterogeneity in findings. Objectives: This study aims to investigate the association of CAs, PTEs, and PTSD with TL and HCC in a high-risk sample of young adults who were previously placed in youth residential care institutions throughout Switzerland. Method: Our sample includes 130 participants (30.8% women, M Age = 26.5 ± 3.7 years) with previous youth residential care placements (MPlacements= 3.9). CAs and PTEs, as well as PTSD, were assessed with self-reported questionnaires and semi-structured clinical interviews. Immune cell TL was measured with quantitative polymerase chain reaction (qPCR) in whole blood. Hair samples were collected for HCC measurement and assayed with high-sensitivity ELISA. Multivariate regression models were fitted to describe the associations between CAs, PTEs, and PTSD with TL and HCC, adjusting for covariates. Results: In our high-risk sample, a higher burden of CAs, PTEs, Criterion A trauma, and PTSD was associated with longer TL. PTEs, Criterion A trauma, and PTSD were associated with lower HCC, however no significant associations between CAs and HCC were found. The magnitude of these effects varied depending on the dimensional or categorical nature of the stress-phenotype and the specific measure used. Conclusions: Our findings are in contrast with many, but not all, previous studies of associations between adversity and both TL and HCC. For instance, our findings are in line with other studies that find a state of hypocortisolism in PTSD. Better measurement of adversities and trauma, multisystem biomarker approaches, and more research in larger high-risk samples at the upper end of the adversity-continuum is warranted.

Identifying correlates of suicide ideation during the COVID-19 pandemic: A cross-sectional analysis of 148 sociodemographic and pandemic-specific factors.

The coronavirus disease 2019 (COVID-19) pandemic has created a global health crisis, with disproportionate effects on vulnerable sociodemographic groups. Although the pandemic is showing potential to increase suicide ideation (SI), we know little about which sociodemographic characteristics or COVID-19 experiences are associated with SI. Our United States-based sample (n = 837 adults [mean age = 37.1 years]) completed an online survey during August-September 2020. The study utilized an online convenience sample from a prior study, which was enriched for exposure to trauma and experiences of posttraumatic stress symptoms. We assessed SI using the Beck Depression Inventory-II. Traditional (i.e., logistic regression) and machine learning (i.e., LASSO, random forest) methods evaluated associations of 148 self-reported COVID-19 factors and sociodemographic characteristics with current SI. 234 participants (28.0%) reported SI. Twenty items were significantly associated with SI from logistic regression. Of these 20 items, LASSO identified seven sociodemographic characteristics (younger age, lower income, single relationship status, sexual orientation other than heterosexual as well as specifically identifying as bisexual, non-full-time employment, and living in a town) and six COVID-19 factors (not engaging in protective COVID-19 behaviors, receiving mental health treatment (medication and/or psychotherapy) due to the COVID-19 pandemic, socializing during the pandemic, losing one's job due to COVID-19, having a friend with COVID-19, and having an acquaintance with COVID-19) associated with SI. Random forest findings were largely consistent with LASSO. These findings may inform multidisciplinary research and intervention work focused on understanding and preventing adverse mental health outcomes such as SI during and in the aftermath of the pandemic.

Higher hair cortisol concentrations associated with shorter leukocyte telomere length in high-risk young adults.

Chronic stress is associated with accelerated biological aging as indexed by short age-adjusted leukocyte telomere length (LTL). Exploring links of biological stress responses with LTL has proved challenging due to the lack of biological measures of chronic psychological stress. Hair cortisol concentration (HCC) has emerged as a measure of chronic hypothalamic pituitary adrenal (HPA) axis activation, allowing the examination of relationships between aggregate cortisol concentrations over time and LTL. Our sample includes 92 participants (38% women, Mage = 26 ± 3.7 years) from a high-risk sample of young adults with previous residential care placements. Two cm hair was collected for HCC, reflecting approximately eight weeks of cortisol secretion. LTL was measured with quantitative polymerase chain reaction (qPCR) in whole blood samples. All samples for LTL were run in triplicate and assayed twice. Linear and polynomial regression models were used to describe the association between HCC and LTL, adjusting for age and sex. HCC and LTL showed negative associations (std. ß = - 0.67, 95% CI [- 0.83, - 0.52], p < .001) in age- and sex-adjusted analyses, indicating that higher HCCs are associated with shorter LTL. Using polynomial regression, we found a curvilinear relationship indicating a stronger negative association at lower cortisol concentrations. Higher HCCs were associated with shorter LTL, supporting the hypothesized involvement of prolonged cortisol secretion in telomere attrition. Thus, HCC may prove useful as a biological indicator of chronic stress associated with aging-related processes in samples exposed to high levels of stress.

Psilocybin for Trauma-Related Disorders.

Posttraumatic stress disorder (PTSD) is a debilitating, chronic disorder and efficacy rates of current PTSD treatments are underwhelming. There is a critical need for innovative approaches. We provide an overview of trauma and PTSD and cite literature providing converging evidence of the therapeutic potential of psilocybin for PTSD. No study to date has investigated psilocybin or psilocybin-assisted psychotherapy (PAP) as treatments for PTSD. An open-label study in traumatized AIDS survivors found that PAP reduced PTSD symptoms, attachment anxiety, and demoralization. Several PAP trials show preliminary efficacy in facilitating confronting traumatic memories, decreasing emotional avoidance, depression, anxiety, pessimism, and disconnection from others, and increasing acceptance, self-compassion, and forgiveness of abusers, all of which are relevant to PTSD recovery. There is also early evidence that other classic psychedelics may produce large reductions in PTSD symptoms in combat veterans. However, this body of literature is small, mechanisms are not yet well understood, and the risks of using psychedelic compounds for trauma-related disorders need further study. In sum, evidence supports further investigation of PAP as a radically new approach for treating PTSD.

Prior trauma exposure, posttraumatic stress symptoms, and COVID-19 vaccine hesitancy.

Understanding correlates of COVID-19 vaccine intentions is critical for increasing vaccine uptake. Given associations of trauma exposure and posttraumatic stress disorder (PTSD) with alterations in threat sensitivity and health behaviors, we hypothesized they could influence COVID-19 vaccine acceptance and hesitancy and be important variables to consider in the design of vaccination campaigns. Data came from a longitudinal online study of 544 US adults with high levels of pre-pandemic trauma and PTSD, assessed in August/September 2020 and March/April 2021. Individuals reported socio-demographic factors, pandemic factors, lifetime trauma history and PTSD symptoms, and COVID-19 vaccinations or intentions. We estimated bivariate associations between socio-demographics, pandemic factors, and trauma and PTSD symptoms at baseline and follow-up with COVID-19 vaccine acceptance versus hesitancy (i.e., vaccinated against COVID-19 or willing to get vaccinated versus unsure or unwilling to get vaccinated) six months later. Multiple socio-demographics (e.g., race/ethnicity, income, education, political preference) and pandemic factors (e.g., perceived likelihood of infection, household COVID-19 infection) were associated with COVID-19 vaccine hesitancy (27.2% were hesitant). However, trauma history, PTSD symptoms, and other mental health factors were not associated with COVID-19 vaccine acceptance versus hesitancy. Socio-demographic and pandemic-related factors appear more important than trauma or mental health for understanding COVID-19 vaccine intentions.

Association of Psychiatric Disorders With Incidence of SARS-CoV-2 Breakthrough Infection Among Vaccinated Adults.

Importance: Psychiatric disorders may be associated with an increased risk for SARS-CoV-2 breakthrough infection after vaccination, but no studies have tested this hypothesis. Objective: To evaluate whether past diagnoses of psychiatric disorders are associated with an increased incidence of SARS-CoV-2 breakthrough infection among fully vaccinated individuals. Design, Setting, and Participants: This retrospective cohort study included data from the administrative and electronic health records of US Department of Veterans Affairs (VA) patients from February 20, 2020, to November 16, 2021. Participants included 263 697 patients who accessed VA health care during the study period, had at least 1 SARS-CoV-2 test recorded in the electronic health record, had no record of SARS-CoV-2 infection prior to vaccination, and had completed a full SARS-CoV-2 vaccination regimen 14 days or more prior. Exposures: Psychiatric disorder diagnoses in the past 5 years, including depressive, posttraumatic stress, anxiety, adjustment, alcohol use, substance use, bipolar, psychotic, attention-deficit/hyperactivity, dissociative, and eating disorders. Main Outcomes and Measures: SARS-CoV-2 breakthrough infections, defined as positive SARS-CoV-2 tests, among fully vaccinated individuals. Results: Of 263 697 fully vaccinated VA patients (239 539 men [90.8%]; mean [SD] age, 66.2 [13.8] years), 135 481 (51.4%) had at least 1 psychiatric disorder diagnosis, and 39 109 (14.8%) developed a breakthrough infection. A diagnosis of any psychiatric disorder was associated with increased incidence of breakthrough infection, both in models adjusted for potential confounders (adjusted relative risk [aRR], 1.07; 95% CI, 1.05-1.09) and additionally adjusted for medical comorbidities and smoking (aRR, 1.03; 95% CI, 1.01-1.05). Most specific psychiatric disorder diagnoses were associated with an increased incidence of breakthrough infection, with the highest relative risk observed for adjustment disorder (aRR, 1.13; 95% CI, 1.10-1.16) and substance use disorders (aRR, 1.16; 95% CI, 1.12-1.21) in fully adjusted models. Stratifying the sample at 65 years of age revealed that associations between psychiatric diagnoses and incident breakthrough infection were present in both age groups but were stronger and robust to adjustment for medical comorbidities and smoking among older patients. Conclusions and Relevance: This cohort study suggests that psychiatric disorder diagnoses were associated with an increased incidence of SARS-CoV-2 breakthrough infection among VA patients, with the strongest associations observed for older individuals. Individuals with psychiatric disorders may be at heightened risk for contracting COVID-19 even after vaccination, suggesting the need for targeted prevention efforts.

Posttraumatic stress disorder symptoms associated with protective and risky behaviors for coronavirus disease 2019.

OBJECTIVE: Psychiatric disorders increase risk for contracting coronavirus disease 2019 (COVID-19), but we know little about relationships between psychiatric symptoms and COVID-19 risky and protective behaviors. Posttraumatic stress disorder (PTSD) has been associated with increased propensity to engage in risky behaviors, but may also be associated with increased COVID-19 protective behaviors due to increased threat sensitivity and social isolation. METHOD: We examined associations of PTSD symptoms with COVID-19-related protective and risky behaviors using data from a cross-sectional online United States study among 845 US adults in August through September 2020. PTSD symptoms (PTSD Checklist-5), sociodemographics, COVID-19-related experiences and vulnerabilities, and past 30-day engagement in 10 protective and eight risky behaviors for COVID-19 were assessed via self-report. We examined associations between PTSD symptoms and COVID-19 protective and risky behaviors with linear regressions, adjusting for covariates. RESULTS: Probable PTSD and higher PTSD symptom severity were associated with greater engagement in protective behaviors, but also greater engagement in risky behaviors. Associations were only slightly attenuated by adjustment for COVID-19 exposures and perceived likelihood and severity of COVID-19. Associations varied by PTSD clusters: intrusions and arousal were associated with both more protective and more risky behaviors, whereas negative cognitions or mood was associated only with more risky, and avoidance only with more protective, behaviors. CONCLUSION: Higher PTSD symptoms were associated with engagement in more protective but also more risky behaviors for COVID-19. Mental health should be considered in the design of public health campaigns dedicated to limiting infectious disease spread. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Worse sleep, worsening post-traumatic stress disorder (PTSD): Poor sleep quality associated with increases in PTSD symptoms amongst those experiencing high threat of the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic is a global health crisis with the potential to elicit and worsen psychiatric symptoms, particularly post-traumatic stress disorder (PTSD) symptoms. Identifying modifiable protective factors is critical for preventing and treating PTSD symptoms both during and following the COVID-19 pandemic. The present study examined associations of self-reported sleep quality and anticipatory threat appraisals of the pandemic with PTSD symptoms 6 months later in a sample enriched for pre-pandemic trauma exposure and PTSD. The sample included 590 adults (mean age 38.2 years) who completed a baseline survey in August/September 2020 and follow-up survey in March/April 2021. The sample was recruited from a pool of participants interested in a prior study about traumatic stress. Participants self-reported sleep quality and pandemic-related anticipatory threat appraisals at baseline. PTSD symptoms were assessed at baseline and follow-up. Baseline sleep quality was associated with PTSD symptoms at follow-up controlling for baseline PTSD symptoms (B = -2.49, p = 0.001). Perceived anticipatory threat of the pandemic moderated this association such that worse sleep quality was related to more severe PTSD symptoms at follow-up for participants with higher (B = -4.07, p < 0.001) but not lower (B = -0.43, p = 0.679) anticipatory threat about the COVID-19 pandemic. These findings suggest that poor sleep quality may enhance vulnerability to later PTSD symptoms during the pandemic, particularly among those individuals who perceived the pandemic as threatening for their future. Treatments that address sleep problems may be beneficial for reducing trauma-related symptoms during and following the global health crisis.

Effects of oxytocin administration on fear-potentiated acoustic startle in co-occurring PTSD and alcohol use disorder: A randomized clinical trial.

Co-occurring posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is common and particularly associated with elevation of hyperarousal compared to PTSD alone. Treatment options are limited. Oxytocin regulates physiological stress response. Intranasal oxytocin administration has demonstrated potential in reducing symptoms of both PTSD and AUD. This study addresses a gap in the literature by investigating effects of intranasal oxytocin on startle reactivity, an important potential marker of both PTSD and AUD symptomatology. This is a randomized, double-blind, placebo-controlled, within- and between-participant, crossover, dose-ranging study examining the effects of a single administration of oxytocin 20 IU versus 40 IU versus placebo on psychophysiological responses to a common laboratory fear-potentiated acoustic startle paradigm in participants with PTSD-AUD (n = 47) and controls (n = 37) under three different levels of threat. Contrary to our hypothesis, for the PTSD-AUD group, oxytocin 20 IU had no effect on startle reactivity, while oxytocin 40 IU increased measures of startle reactivity. Additionally, for PTSD-AUD only, ambiguous versus low threat was associated with an elevated skin conductance response. For controls only, oxytocin 20 IU versus placebo was associated with reduced startle reactivity.

Clusters of COVID-19 protective and risky behaviors and their associations with pandemic, socio-demographic, and mental health factors in the United States.

Individual behaviors are critical for preventing the spread of coronavirus disease 2019 (COVID-19) infection. Given that both protective and risky behaviors influence risk of infection, it is critical that we understand how such behaviors cluster together and in whom. Using a data-driven approach, we identified clusters of COVID-19-related protective and risky behaviors and examined associations with socio-demographic, pandemic, and mental health factors. Data came from a cross-sectional online U.S. nationwide study of 832 adults with high levels of pre-pandemic trauma. Latent class analysis was performed with ten protective (e.g., washing hands, wearing masks) and eight risky (e.g., attending indoor restaurants, taking a flight) behaviors for COVID-19. Then, we examined distributions of socio-demographic and pandemic factors across behavior classes using ANOVA or Chi-square tests, and associations between mental health factors (depressive, anxiety, posttraumatic stress symptoms) and behavior classes using multinomial logistic regression. We identified four classes, including three classes with relatively low risky but high (28.8%), moderate (33.5%) and minimal (25.5%) protective behaviors and one high risky behaviors class with associated moderate protective behaviors (12.1%). Age, sexual orientation, political preference, and most pandemic factors differed significantly across behavior classes. Anxiety and posttraumatic stress symptoms, but not depression, were higher in the High Risk, but also Highly and Moderately Protective classes, relative to Minimally Protective. Prevention and intervention efforts should examine constellations of protective and risky behaviors to comprehensively understand risk, and consider current anxiety and posttraumatic stress symptoms as potential risk indicators.

Exploring the Gut Microbiota and Cardiovascular Disease.

Cardiovascular disease (CVD) has been classified as one of the leading causes of morbidity and mortality worldwide. CVD risk factors include smoking, hypertension, dyslipidaemia, obesity, inflammation and diabetes. The gut microbiota can influence human health through multiple interactions and community changes are associated with the development and progression of numerous disease states, including CVD. The gut microbiota are involved in the production of several metabolites, such as short-chain fatty acids (SCFAs), bile acids and trimethylamine-N-oxide (TMAO). These products of microbial metabolism are important modulatory factors and have been associated with an increased risk of CVD. Due to its association with CVD development, the gut microbiota has emerged as a target for therapeutic approaches. In this review, we summarise the current knowledge on the role of the gut microbiome in CVD development, and associated microbial communities, functions, and metabolic profiles. We also discuss CVD therapeutic interventions that target the gut microbiota such as probiotics and faecal microbiota transplantation.

Ventromedial and insular cortical volume moderates the relationship between BDNF Val66Met and threat sensitivity.

While the BDNF Val66Met polymorphism has been linked to various trauma and anxiety - related psychiatric disorders, limited focus has been on the neural structures that might modulate its relationship with objective measures of threat sensitivity. Therefore, we assessed whether there was an interaction of Val66Met polymorphism with brain area volumes previously associated with anxiety and PTSD, such as the ventromedial prefrontal cortex (vmPFC), insular cortex (IC), and dorsal and ventral anterior cingulate cortices (dACC and vACC), in predicting fear-potentiated psychophysiological response in a clinical sample of Veterans. 110 participants engaged in a fear-potentiated acoustic startle paradigm and provided genetic and imaging data. Fear conditions included no, ambiguous, and high threat conditions (shock). Psychophysiological response measures included electromyogram (EMG), skin conductance response (SCR), and heart rate (HR). PTSD status, trauma history, and demographics were also assessed. There was an interaction of Met allele carrier status with vmPFC, IC, dACC, and vACC volumes for predicting SCR (p < 0.001 for all regions). However, only vmPFC and IC significantly moderated the relationship between Val66Met and psychophysiological response (SCR). The Val66met polymorphism may increase susceptibility to PTSD and anxiety disorders via an interaction with reduced vmPFC and IC volume. Future research should examine whether these relationships might be associated with a differential course of illness longitudinally or response to treatments.

Long-term dietary intake from infancy to late adolescence is associated with gut microbiota composition in young adulthood.

BACKGROUND: Gut microbiota composition as influenced by long-term diet may be associated with the risk of adult chronic diseases. Thus, establishing the relation of long-term diet, particularly starting from early life, with adult microbiota composition would be an important research advance. OBJECTIVE: We aimed to investigate the association of long-term intake of energy, carbohydrate, fiber, protein, and fat from infancy to late adolescence with microbiota composition in adulthood. METHODS: Within the prospective DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study, we sampled stool 1 or 2 times within 1 y from 128 adults (median age: 29 y). Microbiota composition was profiled by 16S ribosomal RNA sequencing. Annual dietary records from age 1 to 18 y were retrieved. We estimated trajectories of energy, energy-adjusted carbohydrate, fiber, protein, and fat intake with multilevel models, producing predicted intake at age 1 y and rates of change in intake. A multivariate, zero-inflated, logistic-normal model was used to model the association between intake trajectories and the composition of 158 genera in single-sampled individuals. Associations found in this model were confirmed in double-sampled individuals using a zero-inflated Beta regression model. RESULTS: Adjusting for covariates and temporal differences in microbiota composition, long-term carbohydrate intake was associated with 3 genera. Specifically, carbohydrate intake at age 1 y was negatively associated with Phascolarctobacterium [coefficient = -4.31; false discovery rate (FDR)-adjusted P = 0.006] and positively associated with Dialister (coefficient = 3.06; FDR-adjusted P = 0.003), and the rate of change in carbohydrate intake was positively associated with Desulfovibrio (coefficient = 13.16; FDR-adjusted P = 0.00039). Energy and other macronutrients were not associated with any genus. CONCLUSIONS: This work links long-term carbohydrate intake to microbiota composition. Considering the associations of high carbohydrate intake and microbiota composition with some diseases, these findings could inform the development of gut microbiota-targeted dietary recommendations for disease prevention.

Relationships of inflammation trajectories with white matter volume and integrity in midlife.

OBJECTIVE: Elevated inflammation is associated with worse late-life cognitive functioning and brain health. Our goal was to examine the relationship between inflammation trajectories and white matter integrity in midlife. METHODS: Participants were 508 adults from the Coronary Artery Risk Development in Young Adults Study (CARDIA; 51% female). Latent class analysis was used to identify inflammation trajectories based on repeated measures of the inflammatory marker C-reactive protein (CRP) over the 18 years before brain magnetic resonance imaging (MRI). Outcomes were brain MRI measures of total and region-specific white matter volume and integrity at a mean age of 50.6 ± 3.4 years. Linear regression was used to examine if inflammation trajectories were associated with brain MRI outcomes, adjusting for potential confounds in all models and for disease and health behaviors in follow-up models. RESULTS: Lower-stable (38%), moderate-increasing (7%), and consistently-higher (54%), trajectories emerged. Compared to the lower-stable group, the moderate-increasing group showed lower white matter volume (ß = -0.18, 95% CI -0.29, -0.06) and worse white matter integrity as indexed by lower fractional anisotropy (FA; ß = -0.37, 95% CI -0.70, -0.04) and higher mean diffusivity (ß = 0.44, 95% CI 0.11, 0.78) in the whole brain. The consistently-higher group showed lower whole-brain FA (ß = -0.20, -0.38, -0.03). In exploratory analyses, the moderate-increasing group showed lower white matter volume, lower FA and higher MD in the frontal, temporal, and parietal lobes compared to the lower-stable group. The consistently-higher group showed lower white matter volume in the parietal lobe and lower FA in the frontal, temporal, and parietal lobes, but similar MD, compared to the lower-stable group. Findings for the moderate-increasing, but not the consistently-higher, group were robust to adjustment for disease and lifestyle factors. CONCLUSION: Increasing or high inflammation trajectories from early to mid adulthood are associated with worse brain health, as indexed by lower white matter volume and/or worse white matter integrity.

Compounding Stress: Childhood Adversity as a Risk Factor for Adulthood Trauma Exposure in the Health and Retirement Study.

Childhood adversity (CA) and adulthood traumatic experiences (ATEs) are common and unequally distributed in the general population. Early stressors may beget later stressors and alter life-course trajectories of stressor exposure. Gender differences exist regarding the risk of specific stressors. However, few studies have examined the associations between specific types of CA and ATEs. Using a large-scale sample of older adults, we aimed to (a) determine if specific or cumulative CA increased the risk for specific or cumulative ATEs and (b) examine whether these associations were moderated by gender. In a sample from the U.S. Health and Retirement Study (N = 15,717; Mage = 67.57 years, SD = 10.54), cross-sectional Poisson and logistic regression models were fitted to assess the specific and cumulative associations between CA and ATEs. Overall, cumulative CA was associated with a larger risk ratio of ATEs, adjusted for covariates: aRRRs = 1.28, 1.63, and 1.97 for 1, 2, and 3-4 adverse events in childhood, respectively. Cumulative CA was particularly strongly associated with adulthood physical attacks, aOR = 5.66, and having a substance-abusing spouse or child, aOR = 4.00. Childhood physical abuse was the strongest independent risk factor for cumulative ATEs, aRRR = 1.49, and most strongly associated with adulthood physical attacks, aOR = 3.41. Gender moderated the association between cumulative CA and cumulative ATEs, with slightly stronger associations between cumulative CA and ATEs for women than men. Given that CA and ATEs perpetuate health disparities worldwide, reducing their incidence and effects should be major priorities for public health.

Enduring neurobehavioral effects induced by microbiota depletion during the adolescent period.

The gut microbiota is an essential regulator of many aspects of host physiology. Disruption of gut microbial communities affects gut-brain communication which ultimately can manifest as changes in brain function and behaviour. Transient changes in gut microbial composition can be induced by various intrinsic and extrinsic factors, however, it is possible that enduring shifts in the microbiota composition can be achieved by perturbation at a timepoint when the gut microbiota has not fully matured or is generally unstable, such as during early life or ageing. In this study, we investigated the effects of 3-week microbiota depletion with antibiotic treatment during the adolescent period and in adulthood. Following a washout period to restore the gut microbiota, behavioural and molecular hallmarks of gut-brain communication were investigated. Our data revealed that transient microbiota depletion had long-lasting effects on microbiota composition and increased anxiety-like behaviour in mice exposed to antibiotic treatment during adolescence but not in adulthood. Similarly, gene expression in the amygdala was more severely affected in mice treated during adolescence. Taken together these data highlight the vulnerability of the gut microbiota during the critical adolescent period and the long-lasting impact manipulations of the microbiota can have on gene expression and behaviour in adulthood.