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A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls.
This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate.
ES-SCZ was associated with the GAF dimensions in patients (symptom: B = −1.53, p-value = 0.001; disability: B = −1.44, p-value = 0.001), siblings (symptom: B = −3.07, p-value < 0.001; disability: B = −2.52, p-value < 0.001), and healthy controls (symptom: B = −1.50, p-value < 0.001; disability: B = −1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group.
Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.
There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation.
We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls.
The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: −0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465).
The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.
This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation.
Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses.
JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences.
These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.
First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment.
This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions.
A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions.
Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.
The mental health and social functioning of millions of forcibly displaced individuals worldwide represents a key public health priority for host governments. This is the first longitudinal study with a representative sample to examine the impact of interpersonal trust and psychological symptoms on community engagement in refugees.
Participants were 1894 resettled refugees, assessed within 6 months of receiving a permanent visa in Australia, and again 2–3 years later. Variables measured included post-traumatic stress disorder symptoms, depression/anxiety symptoms, interpersonal trust and engagement with refugees’ own and other communities.
A multilevel path analysis was conducted, with the final model evidencing good fit (Comparative Fit Index = 0.97, Tucker–Lewis Index = 0.89, Root Mean Square Error of Approximation = 0.05, Standardized Root-Mean-Square-Residual = 0.05). Findings revealed that high levels of depression symptoms were associated with lower subsequent engagement with refugees’ own communities. In contrast, low levels of interpersonal trust were associated with lower engagement with the host community over the same timeframe.
Findings point to differential pathways to social engagement in the medium-term post-resettlement. Results indicate that depression symptoms are linked to reduced engagement with one's own community, while interpersonal trust is implicated in engagement with the broader community in the host country. These findings have potentially important implications for policy and clinical practice, suggesting that clinical and support services should target psychological symptoms and interpersonal processes when fostering positive adaptation in resettled refugees.
Invasive rodents detrimentally affect native bird species on many islands worldwide, and rodent eradication is a useful tool to safeguard endemic and threatened species. However, especially on tropical islands, rodent eradications can fail for various reasons, and it is unclear whether the temporary reduction of a rodent population during an unsuccessful eradication operation has beneficial effects on native birds. Here we examine the response of four endemic land bird species on subtropical Henderson Island in the Pitcairn Island Group, South Pacific Ocean, following an unsuccessful rodent eradication in 2011. We conducted point counts at 25 sampling locations in 14 survey periods between 2011 and 2015, and modelled the abundance trends of all species using binomial mixture models accounting for observer and environmental variation in detection probability. Henderson Reed Warbler Acrocephalus taiti more than doubled in abundance (2015 population estimate: 7,194-28,776), and Henderson Fruit Dove Ptilinopus insularis increased slightly between 2011 and 2015 (2015 population estimate: 4,476–10,072), while we detected no change in abundance of the Henderson Lorikeet Vini stepheni (2015 population estimate: 554–3014). Henderson Crake Zapornia atra increased to pre-eradication levels following anticipated mortality during the operation (2015 population estimate: 4,960–20,783). A temporary reduction of rat predation pressure and rat competition for fruit may have benefitted the reed warbler and the fruit dove, respectively. However, a long drought may have naturally suppressed bird populations prior to the rat eradication operation in 2011, potentially confounding the effects of temporary rat reduction and natural recovery. We therefore cannot unequivocally ascribe the population recovery to the temporary reduction of the rat population. We encourage robust monitoring of island biodiversity both before and after any management operation to better understand responses of endemic species to failed or successful operations.
This paper highlights major developments over the past two to three decades in the neuropsychology of movement and its disorders. We focus on studies in healthy individuals and patients, which have identified cognitive contributions to movement control and animal work that has delineated the neural circuitry that makes these interactions possible. We cover advances in three major areas: (1) the neuroanatomical aspects of the “motor” system with an emphasis on multiple parallel circuits that include cortical, corticostriate, and corticocerebellar connections; (2) behavioral paradigms that have enabled an appreciation of the cognitive influences on the preparation and execution of movement; and (3) hemispheric differences (exemplified by limb praxis, motor sequencing, and motor learning). Finally, we discuss the clinical implications of this work, and make suggestions for future research in this area. (JINS, 2017, 23, 768–777)
We present a tapped tunable delay line filter for radiofrequency (RF) photonic filtering applications, capable of rapid tunability over a wide RF bandwidth limited only by the optical components’ losses, while maintaining independence from polarization state. Multiple fiber taps with contrasting dispersion slopes are used in intensity-modulated direct detection microwave photonic links. A temporal delay is generated between the signals within each arm of the link. Once a signal is received using balanced differential detection, nulls are generated as a function of the laser's operating wavelength. Tuning of the laser allows for a rapid shifting of the nulls in the RF spectrum to dynamically mitigate co-site interference. Through this method we demonstrate the potential for rapid tunability over the RF spectrum by the variation of the operating wavelength of the optical carrier.
This volume not only defines medievalism's margins, as well as its role in marginalizing other fields, ideas, people, places, and events, but also provides tools and models for exploring those issues and indicates new subjects to which they might apply. The eight opening essays address the physical marginalizing of medievalism in annotated texts on medieval studies; the marginalism of oneself via medievalism; medievalism's dearth of ecotheory and religious studies; academia's paucity of pop medievalism; and the marginalization of races, ethnicities, genders, sexual orientations, and literary characters in contemporary medievalism. The seven subsequent articles build on this foundation while discussing: the distancing of oneself (and others) during imaginary visits to the Middle Ages; lessons from the margins of Brazilian medievalism; mutual marginalization among factions of Spanish medieval studies; and medievalism in the marginalization of lower socio-economic classes in late-eighteenth- and early nineteenth-century Spain, of modern gamers, of contemporary laborers, and of Alfred Austin, a late-nineteenth- and early twentieth-century poet also known as Alfred the Little. In thus investigating the margins of and marginalization via medievalism, the volume affirms their centrality to the field. Karl Fugelso is Professor of Art History at Towson University in Baltimore, Maryland. Contributors: Nadia R. Altschul, Megan Arnott, Jaume Aurell, Juan Gomis Coloma, Elizabeth Emery, Vincent Ferré, Valerie B. Johnson, Alexander L. Kaufman, Erin Felicia Labbie, VickieLarsen, Kevin Moberly, Brent Moberly, Alicia C. Montoya, Serina Patterson, Jeff Rider, Lindsey Simon-Jones, Richard Utz, Helen Young.