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Evidence suggests that both childhood trauma and perceived stress are risk factors for the development of psychosis, as well as negative symptoms such as anhedonia. Previous findings link increases in perceived stress to anhedonia in individuals at clinical high risk for psychosis (CHR) and depression; however, the role of childhood trauma in this relationship has not yet been explored, despite consistent evidence that it is associated with sensitisation to later stress.
To examine whether perceived stress mediates the relationship between childhood trauma and anhedonia in a group of youth at CHR as well as in controls (groups with depression and with no diagnosed mental health concerns).
The study used multigroup mediation to examine the indirect effects of childhood trauma on anhedonia via perceived stress in CHR (n = 117) and depression groups (n = 284) and non-psychiatric controls (n = 124).
Perceived stress mediated the relationship between childhood trauma and consummatory anhedonia regardless of group status. Perceived stress mediated the relationship between childhood trauma and anticipatory anhedonia for the CHR and depression groups, but not for non-psychiatric controls. Further, groups differed in the magnitude of this relationship, with the effects trending towards stronger for those in the CHR group.
Our findings suggest a potential transdiagnostic pathway through which childhood trauma contributes to anhedonia across severe mental illness.
Dietary fibre modulates gastrointestinal (GI) health and function, providing laxation, shifting microbiota, and altering bile acid (BA) metabolism. Fruit juice production removes the polyphenol- and fibre-rich pomace fraction. The effects of orange and apple pomaces on GI outcomes were investigated in healthy, free-living adults. Healthy adults were enrolled in two double-blinded, crossover trials, being randomised by baseline bowel movement (BM) frequency. In the first trial, subjects (n 91) received orange juice (OJ, 0 g fibre/d) or OJ + orange pomace (OJ + P, 10 g fibre/d) for 4 weeks, separated by a 3-week washout. Similarly, in the second trial, subjects (n 90) received apple juice (AJ, 0 g fibre/d) or AJ + apple pomace (AJ + P, 10 g fibre/d). Bowel habit diaries, GI tolerance surveys and 3-d diet records were collected throughout. Fresh faecal samples were collected from a participant subset for microbiota and BA analyses in each study. Neither pomace interventions influenced BM frequency. At Week 4, OJ + P tended to increase (P = 0·066) GI symptom occurrence compared with OJ, while AJ + P tended (P = 0·089) to increase flatulence compared with AJ. Faecalibacterium (P = 0·038) and Negativibacillus (P = 0·043) were differentially abundant between pre- and post-interventions in the apple trial but were no longer significant after false discovery rate (FDR) correction. Baseline fibre intake was independently associated with several microbial genera in both trials. Orange or apple pomace supplementation was insufficient to elicit changes in bowel habits, microbiota diversity or BA of free-living adults with healthy baseline BM. Future studies should consider baseline BM frequency and habitual fibre intake.
Clinically significant weight gain (CSWG) is associated with increased morbidity and mortality. This study describes CSWG and comorbidities observed in patients with bipolar I disorder (BD-I) and schizophrenia (SZ) after initiating select second-generation antipsychotics (SGAs).
Percent change in weight, CSWG (=7% weight increase), and incident comorbidities within 12 months of treatment were assessed among patients initiating oral SGAs of moderate-to-high weight gain risk using medical records/claims (OM1 Real-World Data Cloud; January 2013-February 2020). Oral SGAs included clozapine (SZ), iloperidone (SZ), paliperidone (SZ), olanzapine, olanzapine/fluoxetine (BD-I), quetiapine, and risperidone. Outcomes were stratified by baseline body mass index and reported descriptively.
Among patients with BD-I (N = 9142) and SZ (N = 8174), approximately three-quarters were overweight/obese at baseline. During treatment (mean duration = 30 weeks), average percent weight increase was 3.7% (BD-I) and 3.3% (SZ). Average percent weight increase was highest for underweight/normal weight patients (BD-I = 5.5%; SZ = 4.8%), followed by overweight (BD-I = 3.8%; SZ = 3.4%) and obese patients (BD-I = 2.7%; SZ = 2.3%). Within 3 months of treatment, 12% of all patients experienced CSWG. A total of 11.3% (BD-I) and 14.7% (SZ) of patients developed coronary artery disease, hypertension, dyslipidemia, or type 2 diabetes within 12 months of treatment; development of comorbidities was highest among overweight/obese patients and those with CSWG.
Patients who were underweight/normal weight at baseline had the greatest percent change in weight during treatment. Increased comorbidities were observed within 12 months of treatment, specifically among overweight/obese patients and those with CSWG. The magnitude of weight gain and development of comorbidities were similar for patients with BD-I and SZ.
OBJECTIVES/GOALS: Studies have shown that SARS-CoV-2 specific memory B cells can be maintained at least a year after exposure. However, reports show an altered B cell response during infection in severe COVID-19 cases. This study aims to describe the B cell response during COVID-19 convalescence with a focus on signatures that contribute to durable and robust immunity. METHODS/STUDY POPULATION: Our study cohort consisted of individuals who had recovered from non-severe (hospitalized) or severe (hospitalized and requiring invasive mechanical ventilation) COVID-19. In our comparative analysis, samples from both groups were carefully matched to fall within 4-5 weeks post-symptom onset. We also performed a longitudinal analysis of non-severe patients with sampling ending 5 months post-symptom onset. Using high parameter flow cytometry, we characterized the phenotype of memory B cells using 19 distinct cell markers and fluorescently labeled probes to identify B cells reactive with SARS-CoV-2 spike and receptor-binding domain protein. Additionally, serum collected from individuals was used to quantify antibody titers. RESULTS/ANTICIPATED RESULTS: The frequency of spike-specific B cells and serum antibody titers were similar between severe and non-severe groups. However, we observed that individuals recovered from severe COVID-19 have a significantly reduced frequency of spike specific IgG+ memory B cells expressing Tbet and FcRL5 (markers associated with long lived immunity). In the non-severe patients, we observed IgG+Tbet+ B cells targeting the spike protein peak at 2-3 weeks post-symptom onset, decrease by almost fifty percent 4-5 weeks post-symptom onset, and return to baseline 5 months post-symptom onset. Our study also validated previous findings of a short-lived primary response of IgM+ B cells targeting the spike protein. DISCUSSION/SIGNIFICANCE: Our findings highlight potential implications for long-term immunity against re-infection or severity of the resulting disease in patients with severe COVID-19. Further investigation will be necessary to determine whether the maintenance of immunological protection is hindered in patients who overcame severe COVID-19.
Alcohol, cannabis, and nicotine use are highly comorbid and alarmingly prevalent in young adults. The hippocampus may be particularly sensitive to substance exposure. This remains largely untested in humans and familial risk may confound exposure effects. We extend prior work on alcohol and hippocampal volume in women by testing common and unique substance use effects and the potential moderating role of sex on hippocampal volume during emerging adulthood. A quasi-experimental cotwin control (CTC) design was used to separate familial risk from exposure consequences.
In a population-based sample of 435 24-year-old same-sex twins (58% women), dimensional measures (e.g. frequency, amount) of alcohol, cannabis, and nicotine use across emerging adulthood were assessed. Hippocampal volume was assessed using MRI.
Greater substance use was significantly associated with lower hippocampal volume for women but not men. The same pattern was observed for alcohol, cannabis, and nicotine. CTC analyses provided evidence that hippocampal effects likely reflected familial risk and the consequence of substance use in general and alcohol and nicotine in particular; cannabis effects were in the expected direction but not significant. Within-pair mediation analyses suggested that the effect of alcohol use on the hippocampus may reflect, in part, comorbid nicotine use.
The observed hippocampal volume deviations in women likely reflected substance-related premorbid familial risk and the consequences of smoking and, to a lesser degree, drinking. Findings contribute to a growing body of work suggesting heightened risk among women toward experiencing deleterious effects of substance exposure on the still-developing young adult hippocampus.
Among patients with schizophrenia (SZ) and bipolar I disorder (BD-I) treated with second-generation antipsychotics (SGAs), clinically-significant weight gain (CSWG) and treatment interruptions (TIs) are challenges that may result in morbidity/mortality.
CSWG and TIs were assessed among patients who initiated oral SGAs of moderate-to-high weight gain risk (no exposure to index SGAs/first-generation antipsychotics for =12 months) using medical records/claims (OM1 Data Cloud; January 2013-February 2020). Outcomes included CSWG (=7% increase in baseline weight) and TIs (switches [to SGAs of low weight gain risk/long-acting injectables] or discontinuations [no SGAs for >30 days]). Descriptive analyses included proportions of patients with CSWG and TIs, and median time to these outcomes.
Approximately three-quarters of patients were overweight/obese at baseline (SZ: N=8,174; BD-I: N=9,142). Within 3 months of SGA initiation, 12% of all patients experienced CSWG. For patients on treatment with index SGAs for >6 months (SZ: 29%; BD-I: 27%), 28% (SZ) and 30% (BD-I) experienced CSWG during follow-up. Median time to CSWG was 14 weeks. CSWG results were numerically similar among patients with SZ and BD-I.
Over 96% of patients had TIs during follow-up (median time of 12 [SZ] and 13 [BD-I] weeks). Among patients with CSWG and subsequent TIs and weight measurements, 74% did not return to baseline weight after interrupting treatment; the remainder returned to baseline weight with median times of 38 (SZ) and 39 (BD-I) weeks. Results suggest that most patients with CSWG do not return to baseline weight after stopping treatment with oral SGAs of moderate-to-high weight gain risk.
Exposure to childhood maltreatment (CM) may disrupt typical development of neural systems underlying impulse control and emotion regulation. Yet resilient outcomes are observed in some individuals exposed to CM. Individual differences in adult functioning may result from variation in inhibitory control in the context of emotional distractions, underpinned by cognitive–affective brain circuits. Thirty-eight healthy adults with a history of substantiated CM and 34 nonmaltreated adults from the same longitudinal sample performed a Go/No-Go task in which task-relevant stimuli (letters) were presented at the center of task-irrelevant, negative, or neutral images, while undergoing functional magnetic resonance imaging. The comparison group, but not the maltreated group, made increased inhibitory control errors in the context of negative, but not neutral, distractor images. In addition, the comparison group had greater right inferior frontal gyrus and bilateral frontal pole activation during inhibitory control blocks with negative compared to neutral background images relative to the CM group. Across the full sample, greater adaptive functioning in everyday contexts was associated with superior inhibitory control and greater right frontal pole activation. Results suggest that resilience following early adversity is associated with enhanced attention and behavioral regulation in the context of task-irrelevant negative emotional stimuli in a laboratory setting.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
Understanding individual differences in neural responses to stressful environments is an important avenue of research throughout development. These differences may be especially critical during adolescence, which is characterized by opportunities for healthy development and increased susceptibility to the development of psychopathology. While the neural correlates of the psychosocial stress response have been investigated in adults, these links have not been explored during development. Using a new task, the Minnesota Imaging Stress Test in Children (MISTiC), differences in activation are found in fusiform gyrus, superior frontal gyrus, insula, and anterior cingulate cortex when comparing a stressful math task to a nonstressful math task. The MISTiC task successfully elicits cortisol responses in a similar proportion of adolescents as in behavioral studies while collecting brain imaging data. Cortisol responders and nonresponders did not differ in their perceived stress level or behavioral performance during the task despite differences in neuroendocrine function. Future research will be able to leverage the MISTiC task for many purposes, including probing associations between individual differences in stress responses with environmental conditions, personality differences, and the development of psychopathology.
The purpose of this study was to describe the prevalence of hearing loss (HL), vision loss (VL), and dual sensory loss (DSL) in Canadians 45–85 years of age. Audiometry and visual acuity were measured. Various levels of impairment severity were described. Results were extrapolated to the 2016 Canadian population. In 2016, 1,500,000 Canadian males 45–85 years of age had at least mild HL, 1,800,000 had at least mild VL, and 570,000 had DSL. Among females, 1,200,000 had at least mild HL, 2,200,000 had at least mild VL, and 450,000 had DSL. Among Canadians 45–85 years of age, mild, moderate, and severe HL was prevalent among 13.4 per cent, 3.7 per cent, and 0.4 per cent of males, and among 11.3 per cent, 2.3 per cent, and 0.2 per cent of females, respectively. Mild and moderate, or severe VL was prevalent among 19.8 per cent and 2.4 per cent of males, and among 23.9 per cent and 2.6 per cent of females, respectively. At least mild DSL was prevalent among 6.4 per cent of males and 6.1 per cent of females.
To institute facility-wide Kamishibai card (K-card) rounding for central venous catheter (CVC) maintenance bundle education and adherence and to evaluate its impact on bundle reliability and central-line–associated bloodstream infection (CLABSI) rates.
Quality improvement project.
Inpatient units at a large, academic freestanding children’s hospital.
Data for inpatients with a CVC in place for ≥1 day between November 1, 2017 and October 31, 2018 were included.
A K-card was developed based on 7 core elements in our CVC maintenance bundle. During monthly audits, auditors used the K-cards to ask bedside nurses standardized questions and to conduct medical record documentation reviews in real time. Adherence to every bundle element was required for the audit to be considered “adherent.” We recorded bundle reliability prospectively, and we compared reliability and CLABSI rates at baseline and 1 year after the intervention.
During the study period, 2,321 K-card audits were performed for 1,051 unique patients. Overall maintenance bundle reliability increased significantly from 43% at baseline to 78% at 12 months after implementation (P < .001). The hospital-wide CLABSI rate decreased from 1.35 during the 12-month baseline period to 1.17 during the 12-month intervention period, but the change was not statistically significant (incidence rate ratio [IRR], 0.87; 95% confidence interval [CI], 0.60–1.24; P = .41).
Hospital-wide CVC K-card rounding facilitated standardized data collection, discussion of reliability, and real-time feedback to nurses. Maintenance bundle reliability increased after implementation, accompanied by a nonsignificant decrease in the CLABSI rate.
Residential mobility during upbringing, and especially adolescence, is associated with multiple negative mental health outcomes. However, whether associations are confounded by unmeasured familial factors, including genetic liability, is unclear.
We used a population-based case–cohort study to assess whether polygenic risk scores (PRSs) for schizophrenia, bipolar disorder and major depression were associated with mobility from ages 10–14 years, and whether PRS and parental history of mental disorder together explained associations between mobility and each disorder.
Information on cases (n = 4207 schizophrenia, n = 1402 bipolar disorder, n = 18 215 major depression) and a random population sample (n = 17 582), born 1981–1997, was linked between Danish civil and psychiatric registries. Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of separate, large meta-analyses.
PRSs for schizophrenia and major depression were weakly associated with moving once (odds ratio 1.07, 95% CI 1.00–1.16; and odds ratio 1.10, 95% CI 1.04–1.17, respectively), but not twice or three or more times. Mobility was positively associated with each disorder, with more moves associated with greater risk. Adjustment for PRS produced slight reductions in the magnitude of associations. Adjustment for PRS and parental history of mental disorder together reduced estimates by 5–11%. In fully adjusted models mobility was associated with all three disorders; hazard ratios ranged from 1.33 (95% CI 1.08–1.62; one move and bipolar disorder) to 3.05 (95% CI 1.92–4.86; three or more moves and bipolar disorder).
Associations of mobility with schizophrenia, bipolar disorder and depression do not appear to be attributable to genetic liability as measured here. Potential familial confounding of mobility associations may be predominantly environmental in nature.
Although political scientists have increasingly focused on the role of gender in the policy process and the characteristics of individual lobbyists, little is known about the gender politics of the government relations profession. We extend the study of professional women to the unique political context of Washington, DC, lobbying, an important form of political participation that is understudied in terms of gender. Using data from more than 25,000 individuals registered to lobby the federal government from 2008 to 2015, we show that women account for 37% of the lobbyist population in Washington, that female lobbyists are more likely to work as in-house employees than for contract lobbying firms, and that the largest Washington lobbying firms are strongly biased towards employing men. We add to these findings qualitative data from in-depth interviews with 23 lobbyists to reveal how the professional experiences of women often depend on the idiosyncrasies of lobbying employment and the political nature of their work. We conclude that the underrepresentation of women in the professional lobbying community is an underappreciated problem with broader implications for gender equality in elite political participation.
Though theory suggests that individual differences in neuroticism (a tendency to experience negative emotions) would be associated with altered functioning of the amygdala (which has been linked with emotionality and emotion dysregulation in childhood, adolescence, and adulthood), results of functional neuroimaging studies have been contradictory and inconclusive. We aimed to clarify the relationship between neuroticism and three hypothesized neural markers derived from functional magnetic resonance imaging during negative emotion face processing: amygdala activation, amygdala habituation, and amygdala-prefrontal connectivity, each of which plays an important role in the experience and regulation of emotions. We used general linear models to examine the relationship between trait neuroticism and the hypothesized neural markers in a large sample of over 500 young adults. Although neuroticism was not significantly associated with magnitude of amygdala activation or amygdala habituation, it was associated with amygdala–ventromedial prefrontal cortex connectivity, which has been implicated in emotion regulation. Results suggest that trait neuroticism may represent a failure in top-down control and regulation of emotional reactions, rather than overactive emotion generation processes, per se. These findings suggest that neuroticism, which has been associated with increased rates of transdiagnostic psychopathology, may represent a failure in the inhibitory neurocircuitry associated with emotion regulation.
Although there is extensive evidence that problematic alcohol use is associated with smaller hippocampal volume, the typical cross-sectional study design cannot determine whether hippocampal deviations reflect pre-existing liability toward problematic alcohol use or instead reflect an alcohol exposure-related effect. We used the co-twin control study design, which capitalizes upon differences within a twin pair in levels of drinking, to differentiate pre-existing liability from an effect of alcohol exposure.
The sample included 100 female twins, prospectively assessed from ages 11 to 24. Problematic alcohol use was assessed dimensionally and included indicators of quantity, frequency, and density of alcohol use and intoxication. Hippocampal volume was assessed using magnetic resonance imaging.
Problematic alcohol use (proximal and cumulative) was associated with significantly smaller left and right hippocampal volume. Follow-up co-twin control analyses that partitioned individual-level alcohol effects into pre-existing, familial liability and non-shared alcohol exposure-related effects indicated that this association reflected alcohol exposure. Greater alcohol using twins had smaller hippocampal volume relative to lesser alcohol using co-twins, beyond effects of their shared genetic and environmental liability toward problematic alcohol use. Results held accounting for recent alcohol use, other substance use, externalizing and internalizing psychopathology, personality traits, trauma exposure, and menstrual phase.
The association between problematic alcohol use and smaller hippocampal volume likely reflects an alcohol exposure-related effect. Differentiating pre-existing brain deviations that confer risk for problematic alcohol use from those that reflect effects of alcohol on the brain will inform etiological models of addiction and further prevention and intervention efforts.
Research on the cities of the Classical Greek world has traditionally focused on mapping the organisation of urban space and studying major civic or religious buildings. More recently, newer techniques such as field survey and geophysical survey have facilitated exploration of the extent and character of larger areas within urban settlements, raising questions about economic processes. At the same time, detailed analysis of residential buildings has also supported a change of emphasis towards understanding some of the functional and social aspects of the built environment as well as purely formal ones. This article argues for the advantages of analysing Greek cities using a multidisciplinary, multi-scalar framework which encompasses all of these various approaches and adds to them other analytical techniques (particularly micro-archaeology). We suggest that this strategy can lead towards a more holistic view of a city, not only as a physical place, but also as a dynamic community, revealing its origins, development and patterns of social and economic activity. Our argument is made with reference to the research design, methodology and results of the first three seasons of fieldwork at the city of Olynthos, carried out by the Olynthos Project.
To determine risk factors for the development of surgical site infections (SSIs) in neurosurgery patients undergoing spinal fusion.
Retrospective case-control study.
Large, academic, quaternary care center.
The study population included all neurosurgery patients who underwent spinal fusion between August 1, 2009, and August 31, 2013. Cases were defined as patients in the study cohort who developed an SSI. Controls were patients in the study cohort who did not develop an SSI.
To achieve 80% power with an ability to detect an odds ratio (OR) of 2, we performed an unmatched case-control study with equal numbers of cases and controls.
During the study period, 5,473 spinal fusion procedures were performed by neurosurgeons in our hospital. With 161 SSIs recorded during the study period, the incidence of SSIs associated with these procedures was 2.94%. While anterior surgical approach was found to be a protective factor (OR, 0.20; 95% confidence interval [CI], 0.08–0.52), duration of procedure (OR, 1.58; 95% CI, 1.29–1.93), American Society of Anesthesiologists score of 3 or 4 (OR, 1.79; 95% CI, 1.00–3.18), and hospitalization within the prior 30 days (OR, 5.8; 95% CI, 1.37–24.57) were found in multivariate analysis to be independent predictors of SSI following spinal fusion. Prior methicillin-resistant Staphylococcus aureus (MRSA) nares colonization was highly associated with odds 20 times higher of SSI following spinal fusion (OR, 20.30; 95% CI, 4.64–8.78).
In additional to nonmodifiable risk factors, prior colonization with MRSA is a modifiable risk factor very strongly associated with development of SSI following spinal fusion.
Fontan survivors have depressed cardiac index that worsens over time. Serum biomarker measurement is minimally invasive, rapid, widely available, and may be useful for serial monitoring. The purpose of this study was to identify biomarkers that correlate with lower cardiac index in Fontan patients.
Methods and results
This study was a multi-centre case series assessing the correlations between biomarkers and cardiac magnetic resonance-derived cardiac index in Fontan patients ⩾6 years of age with biochemical and haematopoietic biomarkers obtained ±12 months from cardiac magnetic resonance. Medical history and biomarker values were obtained by chart review. Spearman’s Rank correlation assessed associations between biomarker z-scores and cardiac index. Biomarkers with significant correlations had receiver operating characteristic curves and area under the curve estimated. In total, 97 cardiac magnetic resonances in 87 patients met inclusion criteria: median age at cardiac magnetic resonance was 15 (6–33) years. Significant correlations were found between cardiac index and total alkaline phosphatase (−0.26, p=0.04), estimated creatinine clearance (0.26, p=0.02), and mean corpuscular volume (−0.32, p<0.01). Area under the curve for the three individual biomarkers was 0.63–0.69. Area under the curve for the three-biomarker panel was 0.75. Comparison of cardiac index above and below the receiver operating characteristic curve-identified cut-off points revealed significant differences for each biomarker (p<0.01) and for the composite panel [median cardiac index for higher-risk group=2.17 L/minute/m2 versus lower-risk group=2.96 L/minute/m2, (p<0.01)].
Higher total alkaline phosphatase and mean corpuscular volume as well as lower estimated creatinine clearance identify Fontan patients with lower cardiac index. Using biomarkers to monitor haemodynamics and organ-specific effects warrants prospective investigation.
Childhood maltreatment is a serious individual, familial, and societal threat that compromises healthy development and is associated with lasting alterations to emotion perception, processing, and regulation (Cicchetti & Curtis, 2005; Pollak, Cicchetti, Hornung, & Reed, 2000; Pollak & Tolley-Schell, 2003). Individuals with a history of maltreatment show altered structural and functional brain development in both frontal and limbic structures (Hart & Rubia, 2012). In particular, previous research has identified hyperactive amygdala responsivity associated with childhood maltreatment (e.g., Dannlowski et al., 2012). However, less is known about the impact of maltreatment on the relationship between the amygdala and other brain regions. The present study employed an emotion processing functional magnetic resonance imaging task to examine task-based activation and functional connectivity in adults who experienced maltreatment as children. The sample included adults with a history of substantiated childhood maltreatment (n = 33) and comparison adults (n = 38) who were well matched on demographic variables, all of whom have been studied prospectively since childhood. The maltreated group exhibited greater activation than comparison participants in the prefrontal cortex and basal ganglia. In addition, maltreated adults showed increased amygdala connectivity with the hippocampus and prefrontal cortex. The results suggest that the intense early stress of childhood maltreatment is associated with lasting alterations to frontolimbic circuitry.