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On October 3–4, 2023 and September 30–October 1, 2024, the Memorial Sloan Kettering Cancer Center Department of Psychiatry and Behavioral Sciences and Supportive Care Service hosted the 4th and 5th Annual U.S. Celebration of World Hospice and Palliative Care Day (WHPCD) conferences, respectively. This article describes both events and lessons learned in anticipation of the 6th annual conference to be held October 6–7, 2025.
Methods
The 4th and 5th annual events, conference planning team reflection, and attendee evaluation responses are summarized.
Results
Since 2020, the conference has attracted attendees from around the world. Two primary aims continue to guide the event: community building and wisdom sharing at the intersection of art and science. Both the 2023 and 2024 events consisted of 13 unique interactive sessions addressing diverse hospice and palliative care topics delivered by interprofessional experts in palliative care (43 faculty in 2023 and 54 in 2024). Multidisciplinary registrants more than doubled from 764 in 43 countries (2023) to 1678 in 87 countries (2024). Complimentary registration for colleagues in low- and middle-income countries (LMIC), students and trainees, and individuals experiencing financial hardship remains a cornerstone of inclusion and equitable access to the event.
Significance of results
The U.S. WHPCD Conference provides a virtual platform to disseminate high-quality science, honor both clinician and patient and caregiver experiences, and celebrate hospice and palliative care delivery during substantial local and global change across practice and policy domains. We remain committed to ensuring an internationally relevant, culturally diverse, and multidisciplinary and interprofessional agenda that will draw increased participation worldwide during future annual events.
To evaluate the impact of implementing a clinical care guideline for uncomplicated gram-negative bloodstream infections (GN-BSI) within a health system.
Design:
Retrospective, quasi-experimental study.
Setting:
A large academic safety-net institution.
Participants:
Adults (≥18 years) with GN-BSI, defined by at least one positive blood culture for specific gram-negative organisms. Patients with polymicrobial cultures or contaminants were excluded.
Interventions:
Implementation of a GN-BSI clinical care guideline based on a 2021 consensus statement, emphasizing 7-day antibiotic courses, use of highly bioavailable oral antibiotics, and minimizing repeat blood cultures.
Results:
The study included 147 patients pre-intervention and 169 post-intervention. Interrupted time series analysis showed a reduction in the median duration of therapy (–2.3 days, P = .0016), with a sustained decline (slope change –0.2103, P = .005) post-intervention. More patients received 7 days of therapy (12.9%–58%, P < .01), oral antibiotic transitions increased (57.8% vs 72.2%, P < .05), and guideline-concordant oral antibiotic selection was high. Repeat blood cultures decreased (50.3% vs 30.2%, P < .01) without an increase in recurrent bacteremia. No significant differences were observed in 90-day length of stay, rehospitalization, recurrence, or mortality.
Conclusions:
Guideline implementation was associated with shorter antibiotic therapy durations, increased use of guideline-concordant oral antibiotics, and fewer repeat blood cultures without compromising patient outcomes. These findings support the effectiveness of institutional guidelines in standardizing care, optimizing resource utilization, and promoting evidence-based practices in infectious disease management.
Previous studies identified clusters of first-episode psychosis (FEP) patients based on cognition and premorbid adjustment. This study examined a range of socio-environmental risk factors associated with clusters of FEP, aiming a) to compare clusters of FEP and community controls using the Maudsley Environmental Risk Score for psychosis (ERS), a weighted sum of the following risks: paternal age, childhood adversities, cannabis use, and ethnic minority membership; b) to explore the putative differences in specific environmental risk factors in distinguishing within patient clusters and from controls.
Methods
A univariable general linear model (GLS) compared the ERS between 1,263 community controls and clusters derived from 802 FEP patients, namely, low (n = 223) and high-cognitive-functioning (n = 205), intermediate (n = 224) and deteriorating (n = 150), from the EU-GEI study. A multivariable GLS compared clusters and controls by different exposures included in the ERS.
Results
The ERS was higher in all clusters compared to controls, mostly in the deteriorating (β=2.8, 95% CI 2.3 3.4, η2 = 0.049) and the low-cognitive-functioning cluster (β=2.4, 95% CI 1.9 2.8, η2 = 0.049) and distinguished them from the cluster with high-cognitive-functioning. The deteriorating cluster had higher cannabis exposure (meandifference = 0.48, 95% CI 0.49 0.91) than the intermediate having identical IQ, and more people from an ethnic minority (meandifference = 0.77, 95% CI 0.24 1.29) compared to the high-cognitive-functioning cluster.
Conclusions
High exposure to environmental risk factors might result in cognitive impairment and lower-than-expected functioning in individuals at the onset of psychosis. Some patients’ trajectories involved risk factors that could be modified by tailored interventions.
Childhood adversity has been associated with increased peripheral inflammation in adulthood. However, not all individuals who experience early adversity develop these inflammatory outcomes. Separately, there is also a link between various internalizing emotional distress conditions (e.g. depression, anxiety, and fear) and inflammation in adulthood. It is possible the combination of adult emotional distress and past childhood adversity may be uniquely important for explaining psychopathology-related immune dysfunction at midlife.
Methods
Using data from the Midlife in the United States (MIDUS) study (n = 1255), we examined whether internalizing, defined as past 12-month emotional distress symptomatology and trait neuroticism, moderated associations between childhood adversity and heightened inflammation in adulthood. Using latent variable modeling, we examined whether transdiagnostic or disorder-specific features of emotional distress better predicted inflammation.
Results
We observed that childhood adversity only predicted adult inflammation when participants also reported adult internalizing emotional distress. Furthermore, this moderation effect was specific to the transdiagnostic factor of emotional distress rather than the disorder-specific features.
Conclusions
We discuss the possibility that adult internalizing symptoms and trait neuroticism together may signal the presence of temporally stable vulnerabilities that amplify the impact of childhood adversity on midlife immune alterations. The study highlights the importance of identifying emotional distress in individuals who have experienced childhood adversity to address long-term immune outcomes and enhance overall health.
The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.
Methods
Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.
Results
In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.
Conclusions
Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.
Anxiety is a common comorbid feature of late-life depression (LLD) and is associated with poorer global cognitive functioning independent of depression severity. However, little is known about whether comorbid anxiety is associated with a domain-specific pattern of cognitive dysfunction. We therefore examined group differences (LLD with and without comorbid anxiety) in cognitive functioning performance across multiple domains.
Method:
Older adults with major depressive disorder (N = 228, ages 65–91) were evaluated for anxiety and depression severity, and cognitive functioning (learning, memory, language, processing speed, executive functioning, working memory, and visuospatial functioning). Ordinary least squares regression adjusting for age, sex, education, and concurrent depression severity examined anxiety group differences in performance on tests of cognitive functioning.
Results:
Significant group differences emerged for confrontation naming and visuospatial functioning, as well as for verbal fluency, working memory, and inhibition with lower performance for LLD with comorbid anxiety compared to LLD only, controlling for depression severity.
Conclusions:
Performance patterns identified among older adults with LLD and comorbid anxiety resemble neuropsychological profiles typically seen in neurodegenerative diseases of aging. These findings have potential implications for etiological considerations in the interpretation of neuropsychological profiles.
Childhood obesity represents a significant global health concern and identifying its risk factors is crucial for developing intervention programs. Many “omics” factors associated with the risk of developing obesity have been identified, including genomic, microbiomic, and epigenomic factors. Here, using a sample of 48 infants, we investigated how the methylation profiles in cord blood and placenta at birth were associated with weight outcomes (specifically, conditional weight gain, body mass index, and weight-for-length ratio) at age six months. We characterized genome-wide DNA methylation profiles using the Illumina Infinium MethylationEpic chip, and incorporated information on child and maternal health, and various environmental factors into the analysis. We used regression analysis to identify genes with methylation profiles most predictive of infant weight outcomes, finding a total of 23 relevant genes in cord blood and 10 in placenta. Notably, in cord blood, the methylation profiles of three genes (PLIN4, UBE2F, and PPP1R16B) were associated with all three weight outcomes, which are also associated with weight outcomes in an independent cohort suggesting a strong relationship with weight trajectories in the first six months after birth. Additionally, we developed a Methylation Risk Score (MRS) that could be used to identify children most at risk for developing childhood obesity. While many of the genes identified by our analysis have been associated with weight-related traits (e.g., glucose metabolism, BMI, or hip-to-waist ratio) in previous genome-wide association and variant studies, our analysis implicated several others, whose involvement in the obesity phenotype should be evaluated in future functional investigations.
Youth adversity is associated with persistence of depression and anxiety symptoms. This association may be greater for disadvantaged societal groups (such as females) compared with advantaged groups (e.g. males). Given that persistent symptoms are observed across a range of disadvantaged, minoritized, and neurodivergent groups (e.g. low compared with high socio-economic status [SES]), the intersection of individual characteristics may be an important moderator of inequality.
Methods
Data from HeadStart Cornwall (N = 4441) was used to assess the effect of youth adversity on combined symptoms of depression and anxiety (Strengths and Difficulties Questionnaire emotional problems subscale) measured at three time-points in 11–14-year-olds. Latent trajectories and regressions were estimated for eight intersectionality profiles (based on gender, SES, and hyperactivity/inattention), and moderating effects of the individual characteristics and their intersections were estimated.
Results
Youth adversity was associated with higher average depression/anxiety symptoms at baseline (11–12-years) across all intersectionality profiles. The magnitude of effects differed across profiles, with suggestive evidence for a moderating effect of youth adversity on change over time in depression/anxiety symptoms attributable to the intersection between (i) gender and SES; and (ii) gender, SES, and hyperactivity/inattention.
Conclusions
The detrimental effects of youth adversity pervade across intersectionality profiles. The extent to which these effects are moderated by intersectionality is discussed in terms of operational factors. The current results provide a platform for further research, which is needed to determine the importance of intersectionality as a moderator of youth adversity on the development of depression and anxiety symptoms in adolescence.
Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP.
Methods
We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately.
Results
Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia.
Conclusions
Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum.
Late-life depression (LLD) is common and frequently co-occurs with neurodegenerative diseases of aging. Little is known about how heterogeneity within LLD relates to factors typically associated with neurodegeneration. Varying levels of anxiety are one source of heterogeneity in LLD. We examined associations between anxiety symptom severity and factors associated with neurodegeneration, including regional brain volumes, amyloid beta (Aβ) deposition, white matter disease, cognitive dysfunction, and functional ability in LLD.
Participants and Measurements:
Older adults with major depression (N = 121, Ages 65–91) were evaluated for anxiety severity and the following: brain volume (orbitofrontal cortex [OFC], insula), cortical Aβ standardized uptake value ratio (SUVR), white matter hyperintensity (WMH) volume, global cognition, and functional ability. Separate linear regression analyses adjusting for age, sex, and concurrent depression severity were conducted to examine associations between anxiety and each of these factors. A global regression analysis was then conducted to examine the relative associations of these variables with anxiety severity.
Results:
Greater anxiety severity was associated with lower OFC volume (β = −68.25, t = −2.18, p = .031) and greater cognitive dysfunction (β = 0.23, t = 2.46, p = .016). Anxiety severity was not associated with insula volume, Aβ SUVR, WMH, or functional ability. When examining the relative associations of cognitive functioning and OFC volume with anxiety in a global model, cognitive dysfunction (β = 0.24, t = 2.62, p = .010), but not OFC volume, remained significantly associated with anxiety.
Conclusions:
Among multiple factors typically associated with neurodegeneration, cognitive dysfunction stands out as a key factor associated with anxiety severity in LLD which has implications for cognitive and psychiatric interventions.
Newcastle disease (ND) is a notifiable disease affecting chickens and other avian species caused by virulent strains of Avian paramyxovirus type 1 (APMV-1). While outbreaks of ND can have devastating consequences, avirulent strains of APMV-1 generally cause subclinical infections or mild disease. However, viruses can cause different levels of disease in different species and virulence can evolve following cross-species transmission events. This report describes the detection of three cases of avirulent APMV-1 infection in Great Britain (GB). Case 1 emerged from the ‘testing to exclude’ scheme in chickens in Shropshire while cases 2 and 3 were made directly from notifiable avian disease investigations in chicken broilers in Herefordshire and on premises in Wiltshire containing ducks and mixed species, respectively). Class II/genotype I.1.1 APMV-1 from case 1 shared 99.94% identity to the Queensland V4 strain of APMV-1. Class II/genotype II APMV-1 was detected from case 2 while the class II/genotype I.2 virus from case 3 aligned closely with strains isolated from Anseriformes. Exclusion of ND through rapid detection of avirulent APMV-1 is important where clinical signs caused by avirulent or virulent APMV-1s could be ambiguous. Understanding the diversity of APMV-1s circulating in GB is critical to understanding disease threat from these adaptable viruses.
Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis.
Methods
Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0–11 years), and late (12–17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use.
Results
The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord.
Conclusions
Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.
While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis.
Methods
We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case–control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.
We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case–control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case–control status.
Results
Controls (86.1%) and FEPp (75.63%) were most likely to report ‘because of friends’ as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: ‘to feel better’ as their RFUC (χ2 = 50.97; p < 0.001). RFUC ‘to feel better’ was associated with being a FEPp (OR 1.74; 95% CI 1.03–2.95) while RFUC ‘with friends’ was associated with being a control (OR 0.56; 95% CI 0.37–0.83). The path model indicated an association between RFUC ‘to feel better’ with heavy cannabis use and with FEPp-control status.
Conclusions
Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use ‘to feel better’. People who reported their reason for first using cannabis to ‘feel better’ were more likely to progress to heavy use and develop a psychotic disorder than those reporting ‘because of friends’.
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.
Methods
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.
Results
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.
Conclusions
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.
This study aimed to explore the association between hyperglycemia in pregnancy (type 2 diabetes (T2D) and gestational diabetes mellitus (GDM)) and child developmental risk in Europid and Aboriginal women.
PANDORA is a longitudinal birth cohort recruited from a hyperglycemia in pregnancy register, and from normoglycemic women in antenatal clinics. The Wave 1 substudy included 308 children who completed developmental and behavioral screening between age 18 and 60 months. Developmental risk was assessed using the Ages and Stages Questionnaire (ASQ) or equivalent modified ASQ for use with Aboriginal children. Emotional and behavioral risk was assessed using the Strengths and Difficulties Questionnaire. Multivariable logistic regression was used to assess the association between developmental scores and explanatory variables, including maternal T2D in pregnancy or GDM.
After adjustment for ethnicity, maternal and child variables, and socioeconomic measures, maternal hyperglycemia was associated with increased developmental “concern” (defined as score ≥1 SD below mean) in the fine motor (T2D odds ratio (OR) 5.30, 95% CI 1.77–15.80; GDM OR 3.96, 95% CI 1.55–10.11) and problem-solving (T2D OR 2.71, 95% CI 1.05–6.98; GDM OR 2.54, 95% CI 1.17–5.54) domains, as well as increased “risk” (score ≥2 SD below mean) in at least one domain (T2D OR 5.33, 95% CI 1.85–15.39; GDM OR 4.86, 95% CI 1.95–12.10). Higher maternal education was associated with reduced concern in the problem-solving domain (OR 0.27, 95% CI 0.11–0.69) after adjustment for maternal hyperglycemia.
Maternal hyperglycemia is associated with increased developmental concern and may be a potential target for intervention so as to optimize developmental trajectories.
Written constitutions are the norm, unwritten constitutions the rare exception. There is much that can be said as to the commonalities and differences between them. There are, nonetheless, two principal variables that underscore the respective forms of constitution, which in turn impact on the modality of change : the extent to which the constitution is committed to writing, and the extent which the constitution is perceived to be separate from, and superior to, ordinary law.
These twin variables are commonly perceived to be linked. There is empirical warrant for this assumption. The paradigmatic written constitution, which contains the principal constitutional norms in a single document, will commonly also enshrine, expressly or impliedly, constitutional review through which courts subject ordinary statute to review for constitutional compliance; the constitutional norms of the paradigmatic unwritten constitution will normally be found in a plethora of sources, and ordinary statute will customarily have pride of place in the constitutional schema.
There is, however, no a priori normative reason why these twin variables should be linked in this manner. The embodiment of constitutional norms in a canonical document does not predetermine the content of the constitution, nor does it impel the conclusion that constitutional review exercised by a court must be part of the resulting schema. This is exemplified, as will be seen below, by the UK, where some suggestions for the shiftto a written constitution are premised on the assumption that parliamentary sovereignty remains a cornerstone of the constitutional ordering. It is, by parity of reason, equally possible in principle to think of an unwritten constitution, the central features of which are markedly similar to those of the paradigmatic written constitution, such that it is accepted by all relevant players that ordinary legislative power is bounded by certain structural and rights-based precepts that are enforced, inter alia, by the courts. The manner through which this might occur will be considered more fully below.
It follows from the foregoing that while the extent to which constitutional norms are committed to writing is of significance in distinguishing the two forms of constitution, the second variable is more important in normative terms, and shapes the way in which change is effectuated. The contrast in this respect is sharp. The foundational starting point of the standard written constitution is the distinction between law-making through ordinary politics and the constitution; the latter circumscribes the former, such that the terrain of ordinary politics is bounded by the constitution.
Brexit was a complex political process, no less so legally. It entailed five principal legal instruments. There were two treaties, the Withdrawal Agreement (WA), which settled the terms on which the UK left the EU, and the TCA, which contained the detailed provisions as to the relationship between the UK and the EU on trade and other issues. Then there were three principal UK statutes: the European Union (Withdrawal) Act 2018 (EUWA 2018), which dealt with the acquis of EU law within the UK post-withdrawal; the European Union (Withdrawal Agreement) Act 2020 (EUWAA 2020), which gave legal force in UK law to the WA, in part by amending EUWA 2018; and the European Union (Future Relationship) Act 2020 (EUFRA), which incorporated the TCA into UK law. The focus of this chapter is on private rights that flow from the preceding instruments.
Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case–control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD).
Methods
Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons.
Results
In case–control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case–case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54–0.92] and PRS-D (OR = 1.31, 95% CI 1.06–1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23–3.74).
Conclusions
Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.
We describe a cohort of children referred with multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2 and compare this cohort with a 2019 cohort of children with Kawasaki disease.
Methods:
We conducted a retrospective cohort study of 2019 and 2020 referrals to the inflammatory cardiology service at Great Ormond Street Hospital for Children. We compared cardiac and inflammatory parameters of a sub-section of the 2020 cohort who presented with reduced left ventricular ejection fraction with the remainder of the cohort.
Results:
Referrals significantly increased between February and June 2020 compared to 2019 (19.8/30 days versus 3.9/30 days). Frequency of coronary artery aneurysms (11/79 (13.9%) versus 7/47 (14.9%)) or severe coronary artery aneurysms (6/79 (7.6%) versus 3/47 (6.4%)) was similar between 2020 and 2019, respectively. The 2020 cohort was older (median age 9.07 years versus 2.38 years), more likely to be of Black, Asian, or other minority ethnic group (60/76 (78.9%) versus 25/42 (59.5%)), and more likely to require inotropic support (22 (27.5%) versus 0 (0%)). Even children with significantly reduced left ventricular ejection fraction demonstrated complete recovery of cardiac function within 10 days (mean 5.25 days ± 2.7).
Discussion:
We observed complete recovery of myocardial dysfunction and an overall low rate of permanent coronary sequelae, indicating that the majority of children with multisystem inflammatory syndrome in children are unlikely to encounter long-term cardiac morbidity. Although the frequency of myocardial dysfunction and inotropic support requirement is not consistent with a diagnosis of Kawasaki disease, the frequency of coronary artery abnormalities and severe coronary artery abnormalities suggests a degree of phenotypic overlap.
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.
Methods
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.
Results
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).
Conclusions
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.