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Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD.
Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age).
Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD.
Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.
Racial and ethnic disparities in resource use among children with CHD remain understudied. We sought to evaluate associations between race, ethnicity, and resource utilisation in children with CHD.
Materials and methods:
Annual data from the National Health Interview Survey were collected for years 2010–2018. Children with self-reported CHD and Non-Hispanic White race, Non-Hispanic Black race, or Hispanic ethnicity were identified. Resource use in the preceding year was identified with four measures: primary place of care visited when sick, receiving well-child checkups, number of emergency department visits, and number of office visits. Cohort characteristics were compared across racial and ethnic groups using Kruskal–Wallis and Fisher’s exact tests. Multivariable logistic regression was used to determine the association of race and ethnicity with likelihood of having an emergency department visit.
We identified 209 children for the primary analysis. Non-Hispanic Black children had significantly more emergency department visits in the prior year, with 11.1% having ≥6 emergency department visits compared to 0.7% and 5.6% of Non-Hispanic White and Hispanic children. Further, 35.2% of Hispanic children primarily received care at clinics/health centres, compared to 17% of Non-Hispanic White children and 11.1% of Non-Hispanic Black children (p = 0.03). On multivariable analysis, Black race was associated with higher odds of emergency department visit compared to White race (odds ratio = 4.19, 95% confidence interval = 1.35 to 13.04, p = 0.01).
In a nationally comprehensive, contemporary cohort of children with CHD, there were some significant racial and ethnic disparities in resource utilisation. Further work is needed to consider the role of socio-economics and insurance status in perpetuating these disparities.
Early surgical intervention in infants with complex CHD results in significant disruptions to their respiratory, gastrointestinal, and nervous systems, which are all instrumental to the development of safe and efficient oral feeding skills. Standardised assessments or treatment protocols are not currently available for this unique population, requiring the clinician to rely on knowledge based on neonatal literature. Clinicians need to be skilled at evaluating and analysing these systems to develop an appropriate treatment plan to improve oral feeding skill and safety, while considering post-operative recovery in the infant with complex CHD. Supporting the family to re-establish their parental role during the hospitalisation and upon discharge is critical to reducing parental stress and oral feeding success.
Child maltreatment (CM) and migrant status are independently associated with psychosis. We examined prevalence of CM by migrant status and tested whether migrant status moderated the association between CM and first-episode psychosis (FEP). We further explored whether differences in CM exposure contributed to variations in the incidence rates of FEP by migrant status.
We included FEP patients aged 18–64 years in 14 European sites and recruited controls representative of the local populations. Migrant status was operationalized according to generation (first/further) and region of origin (Western/non-Western countries). The reference population was composed by individuals of host country's ethnicity. CM was assessed with Childhood Trauma Questionnaire. Prevalence ratios of CM were estimated using Poisson regression. We examined the moderation effect of migrant status on the odds of FEP by CM fitting adjusted logistic regressions with interaction terms. Finally, we calculated the population attributable fractions (PAFs) for CM by migrant status.
We examined 849 FEP cases and 1142 controls. CM prevalence was higher among migrants, their descendants and migrants of non-Western heritage. Migrant status, classified by generation (likelihood test ratio:χ2 = 11.3, p = 0.004) or by region of origin (likelihood test ratio:χ2 = 11.4, p = 0.003), attenuated the association between CM and FEP. PAFs for CM were higher among all migrant groups compared with the reference populations.
The higher exposure to CM, despite a smaller effect on the odds of FEP, accounted for a greater proportion of incident FEP cases among migrants. Policies aimed at reducing CM should consider the increased vulnerability of specific subpopulations.
We present a novel approach to developing a unified radiocarbon-based chronology for multiple sediment cores from a location where radiocarbon dating is challenging. We used 36 radiocarbon ages from eight terminal Pleistocene and Holocene sediment cores with correlated stratigraphies. Stratigraphic correlation was accomplished using a combination of high-resolution photography, high-resolution X-ray fluorescence-based elemental composition data, and volcanic tephra identification. Results show that despite problems associated with potential contamination or radiocarbon reservoir effect, a useful age-depth model has been created for the correlated lacustrine sections of these eight sediment cores, providing chronological controls for future paleoenvironmental analyses of the cores.
A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone.
We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS − ORexposure − ORPRS + 1] with adjustment for potential confounders.
There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) −1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI −6.25 to 20.88).
Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver disease that accompanies obesity and the metabolic syndrome. Excess fructose consumption can initiate or exacerbate NAFLD in part due to a consequence of impaired hepatic fructose metabolism. Preclinical data emphasized that fructose-induced altered gut microbiome, increased gut permeability, and endotoxemia play an important role in NAFLD, but human studies are sparse. The present study aimed to determine if two weeks of excess fructose consumption significantly alters gut microbiota or permeability in humans.
We performed a pilot double-blind, cross-over, metabolic unit study in 10 subjects with obesity (body mass index [BMI] 30–40 mg/kg/m2). Each arm provided 75 grams of either fructose or glucose added to subjects’ individual diets for 14 days, substituted isocalorically for complex carbohydrates, with a 19-day wash-out period between arms. Total fructose intake provided in the fructose arm of the study totaled a mean of 20.1% of calories. Outcome measures included fecal microbiota distribution, fecal metabolites, intestinal permeability, markers of endotoxemia, and plasma metabolites.
Routine blood, uric acid, liver function, and lipid measurements were unaffected by the fructose intervention. The fecal microbiome (including Akkermansia muciniphilia), fecal metabolites, gut permeability, indices of endotoxemia, gut damage or inflammation, and plasma metabolites were essentially unchanged by either intervention.
In contrast to rodent preclinical findings, excess fructose did not cause changes in the gut microbiome, metabolome, and permeability as well as endotoxemia in humans with obesity fed fructose for 14 days in amounts known to enhance NAFLD.
Perceived discrimination is associated with worse mental health. Few studies have assessed whether perceived discrimination (i) is associated with the risk of psychotic disorders and (ii) contributes to an increased risk among minority ethnic groups relative to the ethnic majority.
We used data from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions Work Package 2, a population-based case−control study of incident psychotic disorders in 17 catchment sites across six countries. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between perceived discrimination and psychosis using mixed-effects logistic regression models. We used stratified and mediation analyses to explore differences for minority ethnic groups.
Reporting any perceived experience of major discrimination (e.g. unfair treatment by police, not getting hired) was higher in cases than controls (41.8% v. 34.2%). Pervasive experiences of discrimination (≥3 types) were also higher in cases than controls (11.3% v. 5.5%). In fully adjusted models, the odds of psychosis were 1.20 (95% CI 0.91–1.59) for any discrimination and 1.79 (95% CI 1.19–1.59) for pervasive discrimination compared with no discrimination. In stratified analyses, the magnitude of association for pervasive experiences of discrimination appeared stronger for minority ethnic groups (OR = 1.73, 95% CI 1.12–2.68) than the ethnic majority (OR = 1.42, 95% CI 0.65–3.10). In exploratory mediation analysis, pervasive discrimination minimally explained excess risk among minority ethnic groups (5.1%).
Pervasive experiences of discrimination are associated with slightly increased odds of psychotic disorders and may minimally help explain excess risk for minority ethnic groups.
Psychosis rates are higher among some migrant groups. We hypothesized that psychosis in migrants is associated with cumulative social disadvantage during different phases of migration.
We used data from the EUropean Network of National Schizophrenia Networks studying Gene-Environment Interactions (EU-GEI) case–control study. We defined a set of three indicators of social disadvantage for each phase: pre-migration, migration and post-migration. We examined whether social disadvantage in the pre- and post-migration phases, migration adversities, and mismatch between achievements and expectations differed between first-generation migrants with first-episode psychosis and healthy first-generation migrants, and tested whether this accounted for differences in odds of psychosis in multivariable logistic regression models.
In total, 249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95% CI 1.06–2.44, p = 0.027) and post-migration social disadvantages (OR 1.89, 95% CI 1.02–3.51, p = 0.044), along with expectations/achievements mismatch (OR 1.14, 95% CI 1.03–1.26, p = 0.014) were all significantly associated with psychosis. Migration adversities (OR 1.18, 95% CI 0.672–2.06, p = 0.568) were not significantly related to the outcome. Finally, we found a dose–response effect between the number of adversities across all phases and odds of psychosis (⩾6: OR 14.09, 95% CI 2.06–96.47, p = 0.007).
The cumulative effect of social disadvantages before, during and after migration was associated with increased odds of psychosis in migrants, independently of ethnicity or length of stay in the country of arrival. Public health initiatives that address the social disadvantages that many migrants face during the whole migration process and post-migration psychological support may reduce the excess of psychosis in migrants.
People living in precarious housing or homelessness have higher than expected rates of psychotic disorders, persistent psychotic symptoms, and premature mortality. Psychotic symptoms can be modeled as a complex dynamic system, allowing assessment of roles for risk factors in symptom development, persistence, and contribution to premature mortality.
The severity of delusions, conceptual disorganization, hallucinations, suspiciousness, and unusual thought content was rated monthly over 5 years in a community sample of precariously housed/homeless adults (n = 375) in Vancouver, Canada. Multilevel vector auto-regression analysis was used to construct temporal, contemporaneous, and between-person symptom networks. Network measures were compared between participants with (n = 219) or without (n = 156) history of psychotic disorder using bootstrap and permutation analyses. Relationships between network connectivity and risk factors including homelessness, trauma, and substance dependence were estimated by multiple linear regression. The contribution of network measures to premature mortality was estimated by Cox proportional hazard models.
Delusions and unusual thought content were central symptoms in the multilevel network. Each psychotic symptom was positively reinforcing over time, an effect most pronounced in participants with a history of psychotic disorder. Global connectivity was similar between those with and without such a history. Greater connectivity between symptoms was associated with methamphetamine dependence and past trauma exposure. Auto-regressive connectivity was associated with premature mortality in participants under age 55.
Past and current experiences contribute to the severity and dynamic relationships between psychotic symptoms. Interrupting the self-perpetuating severity of psychotic symptoms in a vulnerable group of people could contribute to reducing premature mortality.
Congenital heart disease (CHD) is the most common birth defect for infants born in the United States, with approximately 36,000 affected infants born annually. While mortality rates for children with CHD have significantly declined, there is a growing population of individuals with CHD living into adulthood prompting the need to optimise long-term development and quality of life. For infants with CHD, pre- and post-surgery, there is an increased risk of developmental challenges and feeding difficulties. Feeding challenges carry profound implications for the quality of life for individuals with CHD and their families as they impact short- and long-term neurodevelopment related to growth and nutrition, sensory regulation, and social-emotional bonding with parents and other caregivers. Oral feeding challenges in children with CHD are often the result of medical complications, delayed transition to oral feeding, reduced stamina, oral feeding refusal, developmental delay, and consequences of the overwhelming intensive care unit (ICU) environment. This article aims to characterise the disruptions in feeding development for infants with CHD and describe neurodevelopmental factors that may contribute to short- and long-term oral feeding difficulties.
Background: Accurate identification of Clostridioides difficile infections (CDIs) from electronic data sources is important for surveillance. We evaluated how frequently laboratory findings were supported by diagnostic coding and treatment data in the electronic health record. Methods: We analyzed a retrospective cohort of patients in the Veterans’ Affairs Health System from 2006 through 2016. A CDI event was defined as a positive laboratory test for C. difficile toxin or toxin genes in the inpatient, outpatient, or long-term care setting with no prior positive test in the preceding 14 days. Events were classified as incident (no CDI in the prior 56 days), or recurrent (CDI in the prior 56 days) and were evaluated for evidence of clinical diagnosis based on International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) and ICD-10-CM codes and at least 1 dose of an anti-CDI agent (intravenous or oral metronidazole, fidaxomicin, or oral vancomycin). We further assessed the possibility of treatment without testing by quantifying positive laboratory tests and diagnostic codes among inpatients receiving an anti-CDI agent. A course of anti-CDI therapy was defined as continuous treatment with the same drug. Results: Among 119,063 incident and recurrent CDI events, 70,114 (58.9%) had a diagnosis code and 15,850 (13.3%) had no accompanying treatment. The proportion of patients with ICD codes was highest among patients treated with fidaxomicin (82.6% of 906) or oral vancomycin (74.3% of 30,777) and was lower among patients receiving metronidazole (63.3% of 103,231) and those without treatment (29.9% of 15,850). The proportion of events with ICD codes and treatment was similar between incident and recurrent episodes. During the study period, there were ~470,000 inpatient courses of metronidazole, fidaxomicin, and oral vancomycin. Table 1 shows the presence of ICD codes and positive laboratory tests by anti-CDI agents. Among 51,100 courses of oral vancomycin, 51% had an ICD code and 44% had a positive test for C. difficile within 7 days of treatment initiation. Among 1,013 courses of fidaxomicin, 79% had an ICD code and 56% had a positive laboratory test. Conclusions: In this large cohort, there was evidence of substantial CDI treatment without confirmatory C. difficile testing and, to a lesser extent, some positive tests without accompanying treatment or coding. A combination of data sources may be needed to more accurately identify CDI from electronic health records for surveillance purposes.
OBJECTIVES/GOALS: Acute lung Injury (ALI) has long been considered a proceeding event to the development of Acute Respiratory Distress Syndrome (ARDS). Diagnosis of classical ALI and ARDS remains difficult relies on clinical components of the Berlin Criteria, interpretation of radiographs and exclusion of pulmonary edema inducing processes. The precipitating factor for developing ALI involves direct or indirect insult to the lungs. Recent studies have described metalloproteinase-3 (MMP3) to be elevated in plasma samples of patients with lung injury and potentially affected by tobacco use. MMP3 can degrade extracellular matrix components contributing to lung edema and inflammation. This study was conducted to examine the utility of matrix metalloproteinase-3 (MMP3) as a biomarker of lung injury. METHODS/STUDY POPULATION: We conducted a single center, retrospective cohort study of patients admitted to the medical ICU (MICU). De-identified bronchoalveolar fluid (BALF) samples were collected and stored at −80C. Enzymatic activity of MMP3 was determined using a fluorescent resonance energy transfer (FRET) assay. Demographics, comorbidities, evidence of lung injury and patient outcomes were collected. Data were reported with descriptive statistics and data was analyzed with t-tests for statistical significance. RESULTS/ANTICIPATED RESULTS: 55 patient BALF samples were included in the final analysis (mean age 58 +/-17, 58.2% male). 54.5% (n = 30) of patients were determined to have lung injury, 29% (n = 16) of patients had COPD and 45.5% (n = 25) of patients were smokers. MMP3 was higher in patients with lung injury (2363 vs 1052 maxV; p = 0.008). Smoking was associated with decreased MMP3 activity (1231 vs. 2215; p = 0.048). COPD was not associated with differences in MMP3 (1563 vs. 1852; p = 0.605). DISCUSSION/SIGNIFICANCE OF IMPACT: Lung Injury results in elevated MMP3 levels. Smoking was not shown to increase MMP3 levels and may in fact increase them. COPD demonstrated no effect on MMP3 levels. MMP3 levels may vary based on the mode of lung injury (i.e. direct vs indirect) and smoking may impact the activity of the enzyme. Further research should assess activity of MMP3 through different modes of lung injury.
The effectiveness of Emergency Medical Teams (EMTs) is strongly related to their time of arrival, and usually only few teams arrive within 24-48 h postdisaster. The decision to deploy and the scale of deployment rely heavily on context and nature of the event and consequently a rapid assessment of needs/gaps is critical to an appropriate and customized response.
In this study, we describe a desk-based study that provides: (1) knowledge about the medical needs that can be anticipated according to the phases of the disaster that is not rich in literature; and (2) a decision support framework for the deployment of EMTs to earthquakes that combines the results of a literature research and a Delphi study involving the opinion of 12 experts in the field.
The resulting framework is a tool that will help better mapping the configuration to the needs on the ground at the time the team becomes operational in the field and will assist those responsible for deploying and/or accepting EMTs in making informed decisions on deployment after an earthquake.
With additional research the framework approach may be adapted to other types of international relief such as to deploy a Search And Rescue (SAR) team.
First episode psychosis (FEP) patients who use cannabis experience more frequent psychotic and euphoric intoxication experiences compared to controls. It is not clear whether this is consequent to patients being more vulnerable to the effects of cannabis use or to their heavier pattern of use. We aimed to determine whether extent of use predicted psychotic-like and euphoric intoxication experiences in patients and controls and whether this differs between groups.
We analysed data on patients who had ever used cannabis (n = 655) and controls who had ever used cannabis (n = 654) across 15 sites from six countries in the EU-GEI study (2010–2015). We used multiple regression to model predictors of cannabis-induced experiences and to determine if there was an interaction between caseness and extent of use.
Caseness, frequency of cannabis use and money spent on cannabis predicted psychotic-like and euphoric experiences (p ⩽ 0.001). For psychotic-like experiences (PEs) there was a significant interaction for caseness × frequency of use (p < 0.001) and caseness × money spent on cannabis (p = 0.001) such that FEP patients had increased experiences at increased levels of use compared to controls. There was no significant interaction for euphoric experiences (p > 0.5).
FEP patients are particularly sensitive to increased psychotic-like, but not euphoric experiences, at higher levels of cannabis use compared to controls. This suggests a specific psychotomimetic response in FEP patients related to heavy cannabis use. Clinicians should enquire regarding cannabis related PEs and advise that lower levels of cannabis use are associated with less frequent PEs.
The ‘jumping to conclusions’ (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.
A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.
The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI −0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25–0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = −1.7, 95% CI −2.8 to −0.5, p = 0.006), but did not relate to delusions in patients.
Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.
Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients.
We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses.
In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14–0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = −0.22; 95% CI −0.37 to −0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use.
Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.