bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of gas accretion on the radial gas metallicity profile of simulated galaxies
Authors: Collacchioni Florencia , Lagos Claudia D P , Mitchell Peter D , Schaye Joop , Wisnioski Emily , Cora Sofía A , Correa Camila A
Published: May 2020

We study the effect of the gas accretion rate ($\dot{M}_{\rm accr}$) on the radial gas metallicity profile (RMP) of galaxies using the eagle cosmological hydrodynamic simulations, focusing on central galaxies of stellar mass M⋆ ≳ 109 M⊙ at z ≤ 1. We find clear relations between $\dot{M}_{\rm accr}$ and the slope of the RMP (measured within an effective radius), where higher $\dot{M}_{\rm accr}$ are associated with more negative slopes. The slope of the RMPs depends more strongly on $\dot{M}_{\rm accr}$ than on stellar mass, star formation rate (SFR), or gas fraction, suggesting $\dot{M}_{\rm accr}$ to be a more fundamental driver of the RMP slope of galaxies. We find that eliminating the dependence on stellar mass is essential for pinning down the properties that shape the slope of the RMP. Although $\dot{M}_{\rm accr}$ is the main property modulating the slope of the RMP, we find that it causes other correlations that are more easily testable observationally: At fixed stellar mass, galaxies with more negative RMP slopes tend to have higher gas fractions and SFRs, while galaxies with lower gas fractions and SFRs tend to have flatter metallicity profiles within an effective radius.
webPSN v2.0: a webserver to infer fingerprints of structural communication in biomacromolecules
Authors: Felline Angelo , Seeber Michele , Fanelli Francesca
Published: May 2020

A mixed Protein Structure Network (PSN) and Elastic Network Model-Normal Mode Analysis (ENM-NMA)-based strategy (i.e. PSN-ENM) was developed to investigate structural communication in bio-macromolecules. Protein Structure Graphs (PSGs) are computed on a single structure, whereas information on system dynamics is supplied by ENM-NMA. The approach was implemented in a webserver (webPSN), which was significantly updated herein. The webserver now handles both proteins and nucleic acids and relies on an internal upgradable database of network parameters for ions and small molecules in all PDB structures. Apart from the radical restyle of the server and some changes in the calculation setup, other major novelties concern the possibility to: a) compute the differences in nodes, links, and communication pathways between two structures (i.e. network difference) and b) infer links, hubs, communities, and metapaths from consensus networks computed on a number of structures. These new features are useful to identify commonalties and differences between two different functional states of the same system or structural-communication signatures in homologous or analogous systems. The output analysis relies on 3D-representations, interactive tables and graphs, also available for download. Speed and accuracy make this server suitable to comparatively investigate structural communication in large sets of bio-macromolecular systems. URL: http://webpsn.hpc.unimore.it.
Regulatory sharing between estrogen receptor α bound enhancers
Authors: Carleton Julia B , Ginley-Hidinger Matthew , Berrett Kristofer C , Layer Ryan M , Quinlan Aaron R , Gertz Jason
Published: May 2020

The human genome encodes an order of magnitude more gene expression enhancers than promoters, suggesting that most genes are regulated by the combined action of multiple enhancers. We have previously shown that neighboring estrogen-responsive enhancers exhibit complex synergistic contributions to the production of an estrogenic transcriptional response. Here we sought to determine the molecular underpinnings of this enhancer cooperativity. We generated genetic deletions of four estrogen receptor α (ER) bound enhancers that regulate two genes and found that enhancers containing full estrogen response element (ERE) motifs control ER binding at neighboring sites, while enhancers with pre-existing histone acetylation/accessibility confer a permissible chromatin environment to the neighboring enhancers. Genome engineering revealed that two enhancers with half EREs could not compensate for the lack of a full ERE site within the cluster. In contrast, two enhancers with full EREs produced a transcriptional response greater than the wild-type locus. By swapping genomic sequences, we found that the genomic location of a full ERE strongly influences enhancer activity. Our results lead to a model in which a full ERE is required for ER recruitment, but the presence of a pre-existing permissible chromatin environment can also be needed for estrogen-driven gene regulation to occur.
Additional Assessment of Developed Occipital Sinus Using Intraoperative Indocyanine Green Videoangiography for a Safe Foramen Magnum Decompression—Technical Case Report
Authors: Omoto Koji , Takeshima Yasuhiro , Nishimura Fumihiko , Nakagawa Ichiro , Motoyama Yasushi , Park Young-Su , Nakase Hiroyuki
Published: May 2020

BACKGROUND AND IMPORTANCE

Although foramen magnum decompression (FMD) with expansive duraplasty is a popular procedure for treating chiari malformation (CM), the common Y-shaped dural incision can lead to a life-threatening cerebral venous circulation disturbance in patients with a developed occipital sinus. Here, we describe the effectiveness of intraoperative indocyanine green video angiography (ICG-VA) for a CM type 1 (CM1) patient with a highly developed unilateral occipital sinus.

CLINICAL PRESENTATION

A 40-yr-old woman presented with sensory disturbance on the left side of the body. Magnetic resonance imaging (MRI) revealed cerebellar tonsil herniation into the foramen magnum with cervical syringomyelia, and computed tomography additionally revealed skull anomalies: fontanel closure insufficiencies, cranial dysraphism, thin cranial bone, and dentition abnormalities. We diagnosed as symptomatic CM1 with syringomyelia associated with cleidocranial dysplasia, which is a dominantly inherited autosomal bone disease. Cerebral angiography revealed a developed right occipital sinus and hypoplasia of the bilateral transverse sinus. We performed FMD, paying special attention to the developed occipital sinus using ICG-VA to ensure a safe duraplasty. The angiography clearly highlighted a right-sided occipital sinus with a high contrast ratio, and no left-sided occipital sinus was visible. After a dural incision in a unilateral curvilinear fashion was safely completed, expansive duraplasty was performed. The sensory disorders experienced by the patient disappeared postoperatively. Postoperative MRI revealed elevation of the cerebellar tonsil and decreasing of the syringomyelia.

CONCLUSION

Additional assessment using intraoperative ICG-VA provides useful information for a safe FMD, particularly in patients with complicated cerebral venous circulation anomalies.
Clipping of Complex Internal Cerebral Artery Terminus Aneurysm: 2-Dimensional Operative Video
Authors: Hendricks Benjamin K , Spetzler Robert F
Published: May 2020

Internal carotid artery (ICA) bifurcation, or terminus, aneurysms are uncommon, and although they can be accessed with relative ease, clip occlusion of such aneurysms is often challenging due to the close proximity of basal forebrain perforator vessels. This patient had an incidentally discovered ICA terminus aneurysm and elected for microsurgical clipping. A modified orbitozygomatic approach was used to approach the aneurysm. The clipping was significantly complicated by the adherence and close proximity of the recurrent artery of Heubner to the aneurysm dome. Following successful dissection of the artery from the aneurysm dome and complete visualization of the aneurysm neck to avoid violation of perforator flow, successful clip occlusion of the aneurysm was achieved. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
How to select the best: Selection procedures of innovation agencies
Authors: Biegelbauer Peter , Palfinger Thomas , Mayer Sabine
Published: May 2020

Innovation agencies, that is organizations with the primary focus of funding applied research and technological development, evaluate project proposals to select the most promising proposals for funding. At the moment, there is only little verified knowledge available on project evaluation and selection processes of innovation agencies. We want to show how projects are evaluated and selected in these organizations. We want to also make a contribution for better understanding the variety of the utilized processes by pointing out the reasoning behind some of the most important practices. This article therefore focuses on the following questions: How are projects selected in innovation agencies? What are the employed procedures and practices? Are there differences in procedures and practices and what would be the reason for these differences? The basis for answering these questions is a study produced for the European Association of National Innovation Agencies, Taftie. There we have analysed the project selection procedures of 18 programmes run by 12 European innovation agencies. To do so, we have produced an overview of existing selection procedures of the innovation agencies, analysed, and compared the procedures along the stages of a typical selection process. The key points of interest were role of evaluators, selection criteria, ranking procedures, and general process issues.
O8.6. RISK OF HOMELESSNESS AFTER DISCHARGE FROM PSYCHIATRIC WARDS
Authors: Nilsson Sandra , Munk Laursen Thomas , Hjorthøj Carsten , Nordentoft Merete
Published: May 2020

Background

Homelessness is an increasing societal problem in most high-income countries and often linked to mental illness and substance use disorders.

However, there are few high-quality studies examining the risk of homelessness following discharge from in-patient psychiatric treatment. such information might be used as documentation for the need of structural changes to prevent homelessness in people with severe mental illness.

We aimed to analyse the absolute and relative risk of homelessness following discharge from psychiatric wards in Denmark in the period from 2001 to 2015 and to identify high-risk diagnostic groups.

Methods

We did a nationwide, register-based cohort study including people aged 18+ years discharged from psychiatric wards in Denmark between 1 January 2001 and 31 December 2015. We analysed associations between psychiatric diagnoses and the risk of homelessness using survival analysis.

Results

A total of 126,848 psychiatric in-patients were included accounting for 94,835 person-years. The incidence of homelessness one year following discharge was 28.18 (95% CI 26.69–29.75) and 9.27 (95% CI 8.45–10.16) per 1000 person-years at risk in men and women, respectively. The one-year cumulative probability of first homelessness after discharge from psychiatric wards with a schizophrenia disorder was 1.54% (95% CI 1.25–1.88) in males and 0.60% (95% CI 0.40–0.87) in females.

Substance use disorders increased the risk of homelessness after discharge with adjusted incidence rate ratios of 6.60 (95% CI 5.19–8.40) (men) and 13.06 (95% CI 9.31–18.33) (women), compared with depressive disorders. Schizophrenia increased the risk of homelessness after discharge by 1.91 (95% CI 1.29–2.83) and by 2.53 (95% CI 1.41–4.54) in men and women, respectively, also compared with depressive disorders. Prior history of homelessness was an important predictor for homelessness following discharge.

Discussion

The first year following discharge from psychiatric wards is a high-risk period of homelessness, especially when having a substance use disorder or a prior history of homeless shelter contact. Schizophrenia was also an important predictor of homelessness. Improved efforts to prevent homelessness are needed.
O10.1. MATERNAL PRENATAL C-REACTIVE PROTEIN, NEURODEVELOPMENT AND OTHER RISK FACTORS FOR PSYCHOSIS IN ADOLESCENT OFFSPRING IN THE NORTHERN FINLAND BIRTH COHORT 1986
Authors: Ramsay Hugh , Surcel Heljä-Marja , Bjornholm Lassi , Khandaker Golam , Veijola Juha
Published: May 2020

Background

Prenatal infection is associated with brain structural and functional abnormalities, and may increase risk for psychosis through a direct effect on neurodevelopment. Proinflammatory immune response may be a common mechanism through which various infections exert their harmful effect, but studies of prenatal maternal inflammatory markers and offspring neurodevelopment are scarce. We examined the associations of maternal prenatal C-reactive protein (CRP) levels with psychosis risk factors in adolescent offspring including markers of neurodevelopment and cannabis use.

Methods

This study used a longitudinal birth cohort, the Northern Finland Birth Cohort 1986 (NFBC 1986), followed up to age 16 years (n=6,985/9,432, 76% follow-up). CRP was measured in maternal sera collected in pregnancy. In offspring, school performance was measured at age 7 and 16y; psychotic experiences and cannabis use was measured at age 16. Controlling for offspring sex, maternal education level, maternal body mass index during pregnancy, smoking during pregnancy and alcohol use during pregnancy using regression analysis, we tested associations of CRP with offspring measures. We also tested for mediation, specifically if adolescent cannabis use mediated the associations between maternal CRP and offspring psychotic experiences and school performance.

Results

Based on data from a minimum of 4,153 participants, after controlling for offspring sex, maternal education level, maternal body mass index during pregnancy, smoking during pregnancy and alcohol use during pregnancy, maternal CRP was associated with adolescent neurodevelopmental markers, including psychotic experiences (odds ratio=1.13, 95% CI=1.00–1.29) and academic performance at age 16 years (beta=0.063, SE=0.013, 95% CI=0.037–0.089). Maternal CRP was also associated with adolescent cannabis use (odds ratio=1.27, 95% CI=1.11–1.46). Cannabis use appeared to mediate a small amount of the associations between maternal CRP and both psychotic experiences and academic performance.

Discussion

These results support a neurodevelopmental role for maternal prenatal infection and offspring psychosis but also suggest an indirect effect through increasing risk of exposure to cannabis. Maternal infection and immune activation may impact on brain circuitry involved in impulsivity, increasing behaviours such as cannabis use that are separately associated with psychosis. The results of this study give clues regarding the mechanism of the maternal inflammation – psychosis association and add to our understanding of the complex neurodevelopmental processes predating psychosis.
T9. EPIGENETIC PROFILING IN SCHIZOPHRENIA DERIVED HUMAN INDUCED PLURIPOTENT STEM CELLS (HIPSCS) AND NEURONS
Authors: Farrelly Lorna , Zhang Shuangping , Flaherty Erin , Topol Aaron , Schrode Nadine , Bastle Ryan , Bhanu Natarajan , Garcia Benjamin , Li Haitao , Brennand Kristen , Maze Ian
Published: May 2020

Background

Schizophrenia (SCZ) is a severe psychiatric disorder affecting ~1% of the world’s population. It is largely heritable with genetic risk reflected by a combination of common variants of small effect and highly penetrant rare mutations. Chromatin modifications are known to play critical roles in the mediation of many neurodevelopmental processes, and, when disturbed, may also contribute to the precipitation of psychiatric disorders, such as SCZ. While a handful of candidate-based studies have measured changes in promoter-bound histone modifications, few mechanistic studies have been carried out to explore how these modifications may affect chromatin to precipitate behavioral phenotypes associated with the disease.

Methods

We applied an unbiased proteomics approach to evaluate the epigenetic landscape of SCZ in human induced pluripotent stem cells (hiPSC), neural progenitor cells (NPCs) and neurons from SCZ patients vs. matched controls. We utilized proteomics-based, label free liquid chromatography mass spectrometry (LC-MS/MS) on purified histones from these cells and confirmed our results by western blotting in postmortem SCZ cortical brain tissues. Furthermore we validated our findings with the application of histone interaction assays and structural and biophysical assessments to identify and confirm novel chromatin ‘readers’. To relate our findings to a SCZ phenotype we used a SCZ rodent model of prepulse inhibition (PPI) to perform pharmacological manipulations and behavioral assessments.

Results

Using label free mass spectrometry we performed PTM screening of hiPSCs, NPCs and matured neurons derived from SCZ patients and matched controls. We identified, amongst others, altered patterns of hyperacetylation in SCZ neurons. Additionally we identified enhanced binding of particular acetylation ‘reader’ proteins. Pharmacological inhibition of such proteins in an animal model of amphetamine sensitization ameliorated PPI deficits further validating this epigenetic signature in SCZ.

Discussion

Recent evidence indicates that relevance and patterns of acetylation in epigenetics advances beyond its role in transcription and small molecule inhibitors of these aberrant interactions hold promise as useful therapeutics. This study identifies a role for modulating gene expression changes associated with a SCZ epigenetic signature and warrants further investigation in terms of how this early gene expression pattern perhaps determines susceptibility or severity of the SCZ disease trajectory.
T11. CORONARY ARTERY CALCIFICATION IN PEOPLE WITH SCHIZOPHRENIA
Authors: Trab Trine , Ernst Nielsen René , Broendum Froekjaer Jens , Eggert Jensen Svend
Published: May 2020

Background

Coronary artery disease (CAD) is one of the major causes of premature mortality in patients with schizophrenia. Coronary artery calcification (CAC) is an independent predictor of cardiac mortality and CAD in the general population, but has not yet been investigated in patients with schizophrenia. The aim of the present study is to compare CAC quantified by cardiac computed tomography (CT) in patients with schizophrenia to the general population.

Methods

Baseline data from an ongoing prospective cohort study including 200 patients with schizophrenia (ICD-10 diagnoses F20 or F25) diagnosed at least 10 years prior to inclusion (chronic group) and 86 patients with schizophrenia diagnosed within two years prior to inclusion (debut group). Patients in the debut group were matched 1:1 on age, gender and smoking status with psychiatrically healthy controls (PHC). All participants underwent cardiac CT and the CAC was quantified using Agatston Score. Mean CAC in the chronic group was compared to reference CAC scores whilst mean CAC in the debut group was compared to PHC. Information on cardiovascular risk factors, illness history, social and psychiatric conditions were obtained at baseline.

Results

Data is currently being analyzed and results will be presented at the Congress of International Schizophrenia Research Society.

Discussion

If the CAC quantified by CT in patients with schizophrenia differs from the PHC population, it might act as a tool for early detection of CAD in these patients. Thus, the findings of this study might contribute to preventive strategies in order to decrease cardiovascular mortality.
T13. CORNEAL CONFOCAL MICROSCOPY DETECTS NEURAL CHANGES IN SCHIZOPHRENIA
Authors: Woodruff Peter , Ponirakis Georgios , Ghandi Reem , Hussein Amani , Bhagat Anjushri , Petropoulos Ioannis , Khan Adnan , Gad Hoda , Aly Al Sotouhy Ahmed , Own Ahmed , Vattoth Surjith , Ramadan Marwan , Al Hamad Hanadi , Currie James , Malik Rayaz A
Published: May 2020

Background

A combination of neurodevelopmental and degenerative neural changes are likely to underpin positive and negative symptoms in schizophrenia. However, there are currently no validated biomarkers to accurately quantify the extent of neural changes in schizophrenia.

Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique that has been used to demonstrate in vivo corneal nerve fiber abnormalities in a range of peripheral neuropathies and central neurodegenerative disorders including Parkinson’s disease, multiple sclerosis and dementia.

We wished to test the hypothesis that corneal nerve abnormalities occur in patients with schizophrenia, particularly those with negative symptoms and cognitive impairment.

Methods

Patients with DSM-V schizophrenia without other causes of peripheral neuropathy other than metabolic syndrome underwent assessment of clinical ratings (Positive and Negative Symptoms Scale (PANSS), cognitive function (Montreal Cognitive Assessment (MOCA) and Corneal confocal microscopy (CCM), vibration perception threshold (VPT) and sudomotor function testing.

Healthy controls underwent the same assessments apart from PANSS.

Results

55 subjects without (n=38) and with schizophrenia (n=17) with comparable mean age (35.7±8.5 vs 35.6±12.2, P=0.96) were studied.

Patients with schizophrenia had significantly higher body weight (93.9±25.5 vs 77.1±10.1, P=0.02) and lower Low Density Lipoproteins (2.6±1.0 vs 3.4±0.7, P=0.02) compared with healthy controls.

The proportion of gender, systolic and diastolic blood pressure, HbA1c, cholesterol, triglyceride and High Density Lipoproteins were comparable between the two groups.

Patients with schizophrenia had significantly lower corneal nerve fibre density (CNFD, fibers/mm2) (35.6±6.5 vs 23.5±7.8, p<0.0001), branch density (CNBD, branches/mm2) (98.1±30.6 vs 34.4±26.9, p<0.0001), and fibre length (CNFL, mm/mm2) (24.2±3.9 vs 14.3±4.7, p<0.0001) compared with healthy controls but no difference in peripheral neuropathy assessed by VPT and sudomotor function testing.

The area under the Receiver Operating Characteristic Curve (95% CI) of CNFD, CNBD, CNFL to distinguish patients with schizophrenia from healthy controls were 87.0% (76.8–98.2%), 93.2% (84.2–102.3%), 93.2% (84.4–102.1%), respectively.

Discussion

These preliminary results:
T25. THE RELATIONSHIP BETWEEN AGE AT FIRST-EPISODE AND LONGITUDINAL CORTICAL CHANGES IN FIRST-EPISODE PSYCHOSIS: A TWO-YEAR LONGITUDINAL STUDY IN AN ADOLESCENT AND ADULT-ONSET COHORT
Authors: Santonja Javier , Pina-Camacho Laura , Martínez Kenia , Díaz-Caneja Covadonga , Arango Celso , Bernardo Arroyo Miguel , Mezquida Gisela , Janssen Joost , Parellada Mara
Published: May 2020

Background

In a unique deeply phenotyped longitudinal dataset consisting of first-episode psychosis (FEP) patients with a wide age at FEP onset (15 to 35 years) and healthy controls, we aimed to determine whether cortical abnormalities are already present at FEP, whether they progress further over the first two years of the illness, and, if so, whether change patterns are associated with age at first episode.

Methods

Multicenter (four-site) two-year follow-up case-control brain magnetic resonance imaging study; 74 patients with a FEP of less than 12 months’ duration, and 64 healthy controls (matched for age, sex, parental socioeconomic status and handedness) were scanned twice (median time between baseline and follow-up scan 24 months, range [16 – 32]). We computed percentage changes (PC) over follow-up in thickness/area/volume for frontal, temporal, parietal and occipital lobes. We included diagnosis (patient vs. control), age at baseline scan, sex, TBV and site as potential confounders. We conducted post-hoc comparisons for young (≤19y) and adult (>19y) diagnostic pairs (FEP vs healthy controls).

Results

A significant age-by-diagnosis interaction was only found for temporal lobe cortical thickness (CT)-PC (d = -.54, p = .002). Within this lobe, the largest effects for the age x diagnosis interaction were found in the middle (d = -.43, p = .01) and inferior (d = - .48, p = .007) temporal gyrus CT-PC. The younger the patient group, the greater temporal thinning relative to their age-matched control group. The most extreme patient vs. control PC difference (i.e. the largest effect size) was found at an age cut-off of 19 years (d=0.9, p= .01).

Discussion

In individuals with psychosis, the two-year cortical changes that follow the FEP are dependent of age at first episode, with those with an earlier onset showing more severe cortical thinning in the temporal lobe.
T39. IMPAIRED SENSORIMOTOR GATING USING THE ACOUSTIC PREPULSE INHIBITION PARADIGM IN INDIVIDUALS AT A CLINICAL HIGH RISK FOR PSYCHOSIS
Authors: Bo Qijing , Mao Zhen , Tian Qing , Li Weidi , Zhao Lei , Wang Chuanyue
Published: May 2020

Background

Many robust studies on prepulse inhibition (PPI) were conducted in patients with schizophrenia, and, increasingly, evidence has indicated individuals who are at clinical high risk for psychosis (CHR). The specificity of the PPI is insufficient with the classic paradigm. The current study investigated an improved perceived spatial separation PPI (PSSPPI) paradigm in CHR individuals, compared with patients of first-episode schizophrenia (FES) and healthy controls (HC), and the relationship between PPI, demographics, clinical characteristics, and cognitive performance.

Methods

We included 53 FESs, 55 CHR individuals, and 53 HCs. CHRs were rated on the Structured Interview for Prodromal Syndromes (SIPS). The prepulse inhibition measures of perceived spatial co-location PPI (PSCPPI) and PSSPPI paradigms were applied using 60- and 120-ms lead intervals. The MATRICS Consensus Cognitive Battery (MCCB) was used to assess neurocognitive functions.

Results

Compared with HC, the CHR group had lower PSSPPI level (ISI=60 ms, P<0.001; ISI=120 ms, P<.001). PSSPPI showed a large effect size (ES) between CHR and HC (ISI=60 ms, ES=0.91; ISI=120 ms, ES=0.98); on PSSPPI using 60-ms lead interval, ES ranged from small to large from CHR to FES. PPI deficits in CHR were unrelated to demographics, clinical characteristics, and cognition.

Discussion

CHR individuals show a sensorimotor gating deficit similar to FES patients on PSSPPI of the startle response, with greater sensitivity than the classic PPI paradigm. PSSPPI appears a promising objective approach for identifying individuals at clinical high risk for psychosis related to a high risk of transition to schizophrenia.
T46. THE EFFECT OF COMPREHENSIVE COGNITIVE REMEDIATION IN INDIVIDUALS AT ULTRA-HIGH RISK FOR PSYCHOSIS: A SINGLE-BLIND, RANDOMISED, CLINICAL TRIAL (FOCUS)
Authors: Birkedal Glenthoej Louise , Lise Mariegaard , Fagerlund Birgitte , Richardt Jepsen Jens , Dam Kristensen Tina , Wenneberg Christina , Krakauer Kristine , Medalia Alice , Roberts David , Hjorthøj Carsten , Nordentoft Merete
Published: May 2020

Background

Individuals at ultra-high risk (UHR) for psychosis display significant cognitive deficits that constitute a barrier to functional recovery. Applying cognitive remediation (CR) before the onset of manifest psychosis may improve cognition and the clinical and functional prognosis of UHR individuals.

Methods

This randomised, clinical trial randomly assigned 146 UHR individuals aged 18–40 years to treatment as usual (TAU) or TAU plus cognitive remediation. The cognitive remediation consisted of 20-weeks of neurocognitive and social cognitive remediation. Assessments were carried out at 6- and 12-months post baseline. Primary outcome was composite score on the Brief Assessment of Cognition in Schizophrenia (BACS) battery at 6-months.

Results

Between April 2014 and January 2017, 73 UHR individuals were assigned to TAU and 73 were assigned to TAU + cognitive remediation. Compared to the control group, cognitive remediation did not result in significant improvement on the BACS composite score at 6-month follow-up (b=-0.125, 95%CI: -0.23 to 0.172, p=0.41). Nor did the intervention improve secondary outcomes in clinical symptoms or functioning. Exploratory analyses found emotion recognition latencies to be significantly more reduced in the intervention group than the TAU group at 6-months follow-up. At 12-month follow-up the intervention group exhibited significantly better performance on two exploratory outcomes of executive function and visual memory. The participants in the intervention group attended an average of 12 sessions out of 20. No adverse events were reported relating to the intervention.

Discussion

While the brief course of treatment did not impact global cognition, symptoms and functioning measures, treatment related benefit was found in exploratory component neuro- and social cognitive measures. Future studies should evaluate whether more personalized interventions such as the separate application of neurocognitive and social cognitive remediation may produce beneficial effect on cognition and functioning compared to treatment as usual, along with establishing the optimal number of training hours to produce cognitive and functional gains.
T69. CORRELATION BETWEEN PERFORMANCE-BASED AND INTERVIEW-BASED COGNITIVE MEASUREMENTS IN PATIENTS WITH SCHIZOPHRENIA
Authors: Jeon Dong-wook , Jung Do-Un , Kim Sung-Jin , Oh Minkyung , Moon Jung-Joon , Kim Yeon-Sue
Published: May 2020

Background

Deficits in cognitive function are often observed in schizophrenia patients and cause functional disability affecting daily life. The performance-based MATRICS consensus cognitive battery (MCCB) is used to measure the cognitive function of schizophrenia patients. In some situations, interview-based measures such as the Schizophrenia Cognition Rating Scale (SCoRS) may be appropriate. In this study, we analyzed the correlation between the entire MCCB domain and each item of the SCoRS to identify the domains and items most associated to each other when each measure is used.

Methods

Fifty-six clinically stable patients were recruited from day hospitals and outpatient wards. To evaluate cognitive function, we used the MCCB performance-based measure and the SCoRS interview-based measure. Measurements were taken at baseline, and two and three months later. Spearman correlation was computed between each item of the SCoRS Interviewer’s Rating and each MCCB score.

Results

The correlation between the MCCB overall T score and the SCoRS global score was the strongest (r = - 0.52), while that between the SCoRS total score and the MCCB speed of processing score was r = -0.48. The SCoRS global score showed statistically significant correlation with all seven MCCB domains and the overall T score. Similar results were observed for SCoRS item 12.

Discussion

Individual items and total scores of MCCB and SCoRS showed variable degrees of association. If these results are confirmed in larger study samples, a simple item selection to evaluate cognitive function according to the patient’s condition will be possible in a clinical setting.
T99. HARNESSING DIGITAL TECHNOLOGIES TO ASSESS AND TREAT COGNITIVE SYMPTOMS IN SCHIZOPHRENIA
Authors: Shvetz Cecelia , Gu Feng , Drodge Jessica , Torous John , Guimond Synthia
Published: May 2020

Background

Cognitive impairments are a core feature of schizophrenia. Although cognitive impairments have consistently shown to have negative impacts on functional outcomes among individuals with schizophrenia, assessing and treating these symptoms in clinical settings remains a difficult challenge. Interestingly, the growing potential of new digital technologies, such as smartphone applications and virtual reality, hold great promise in alleviating these impairments.

Methods

This presentation will introduce results from two recent studies using digital technologies to assess and treat cognitive symptoms in schizophrenia. In the first study, smartphone versions of the pen-and-paper Trail Making Tests A and B were developed. These cognitive tests measure speed of processing and cognitive flexibility. We assessed the validity of the smartphone versions of both Trail Making Tests in measuring these cognitive domains in in 37 healthy controls and 26 individuals with schizophrenia. Following the initial assessment, participants were asked to complete the two smartphone cognitive tests once a week for three months. This served as a measure of cognitive performance over time

Results

Results showed that it was feasible to measure cognition using a smartphone application in schizophrenia. Performances on both smartphone cognitive tests were significantly and positively correlated with the pen-and-paper versions (Parts A: r = 0.65, p < .001; Parts B: r= 0.44, p= .01). Additionally, significant differences were observed between controls and individuals with schizophrenia on both smartphone tests (Part A: t = -3.88, p = .004; Part B: t = -3.29, p = .002). Moreover, longitudinal results showed no significant effect of practice over time on the smartphone cognitive tests.

Discussion

Digital technologies have the potential to optimize cognitive assessments, monitoring, and care in schizophrenia. Our findings support the feasibility and efficacy of using digital technologies to measure and treat cognitive impairments in schizophrenia. Our research also highlights the importance of including scientists, clinicians, and content experts with schizophrenia in the development of these tools to ensure their validity and facilitate clinical implementation.
T103. THE EFFECT OF VIRTUAL REALITY COGNITIVE BEHAVIORAL THERAPY ON PARANOIA AND MOOD STATES
Authors: Geraets Chris , Snippe Evelien , Van Beilen Marije , Pot-Kolder Roos , Wichers Marieke , van der Gaag Mark , Veling Wim
Published: May 2020

Background

Recently, the efficacy of a novel virtual reality based cognitive behavior therapy (VR-CBT) for paranoia was demonstrated. Evidence is growing that the maintenance of psychosis may be influenced by affective processes. This study examined how treatment with VR-CBT influenced positive and negative affect states, and whether the interplay between mental states was affected.

Methods

The sample consisted of 91 patients with a psychotic disorder randomized either to 16-session individual VR-CBT or treatment as usual. The experience sampling method (ESM; a structured diary technique) was used to assess mental states at baseline, post-intervention and 6-month follow-up. Mixed model analyses were conducted to study treatment effects. Lagged associations between mental states were estimated at baseline and post-intervention, and were visualized with networks.

Results

VR-CBT, but not treatment as usual, resulted in reduced levels of paranoia and negative affect. At pre-intervention networks depicting the dynamic interplay between mental states over time had limited significant connections, with most stable connections being auto-relations. I.e., paranoia was best predicted by paranoia at the previous moment. The dynamic interplay between affective states did not change over time after VR-CBT.

Discussion

We found that VR-CBT specifically targets paranoia and there are indications that VR-CBT had an enduring effect on negative emotions. These beneficial treatment effects do not seem to transfer to positive affective states. Unexpectedly, we did not find evidence that negative mental states such as feeling down or lonely triggered paranoia in the next moment even at pre-intervention, and these temporal relations between mental states did not change over time in response to treatment.
M2. STRESS IS ASSOCIATED AND PREDICTS SCHIZOTYPIC AND PSYCHOTIC-LIKE EXPERIENCES IN THE FLOW OF DAILY LIFE IN NONCLINICAL AND INCIPIENT PSYCHOSIS INDIVIDUALS
Authors: Barrantes-Vidal Neus , Monsonet Manel , Racioppi Anna , Kwapil Thomas R
Published: May 2020

Background

Daily-life stressors, specially of a social nature, seem to play an important role in the origin and expression of the continuum of psychosis vulnerability. This study examined whether social stress and social positive appraisals in daily-life were associated, respectively, with the occurrence and the decrease of momentary psychotic-like and paranoid experiences and symptoms across the psychosis continuum.

Methods

Both social stressors and positive appraisals, as well as psychotic and paranoid experiences, were collected by means of Experience Sampling Methodology over a week. Schizotypy was assessed with the Wisconsin Schizotypy Scales. Participants were 206 nonclinical individuals oversampled for schizotypy scores (mean age=19.8) and 113 individuals with at-risk mental states for psychosis and first episode psychosis (74 and 39, respectively; mean age=22.5).

Results

In the nonclinical sample, appraisals of social stress (but no social contact per se) were associated with psychotic-like and paranoid experiences in daily-life, but not with diminished thoughts or emotions (negative-like symptoms). The association of stress with psychotic and paranoid experiences was moderated by positive, but not negative, schizotypy. In the clinical sample, the positive social appraisal of feeling cared for by others moderated the association between negative self-esteem and the experience of paranoia. Also, they predicted (time-lagged analyses) a decrease of these experiences at subsequent time points—although only feeling cared about did so when the previous level of paranoia was controlled for.

Discussion

Consistent with models postulating that stress-sensitivity is a potential mechanistic pathway of, specifically, the positive dimension of psychosis, situational and also social stress predicted psychotic-like and paranoid experiences only in participants with high positive schizotypy. Furthermore, positive social appraisals showed a critical role for buffering the expression of paranoia associated to poor self-esteem in clinical risk for and early psychosis and predicted its amelioration prospectively. Altogether, these findings support the notion that increased sensitivity to social cues is a critical aspect for both risk and resilience mechanisms in the continuum of psychosis. Additionally, they highlight the powerful relevance of positive social identification for dampening the deleterious effects of poor self-esteem and stress.
M13. INCREASED SAFETY SEEKING IN PATIENTS WITH SCHIZOPHRENIA AND PARANOID THREAT
Authors: Gangl Nicole , Conring Frauke , Walther Sebastian , Rüter Maximilian , Wüthrich Florian , Schäppi Lea , Stegmayer Katharina
Published: May 2020

Background

Schizophrenia is a disabling disorder with tremendous individual burden, reduced quality of life, leading to intense costs for society. Paranoia is a central feature of schizophrenia. In particular, paranoid experience is thought to be associated with aggressive behaviour, and poor social and functional outcome. Since paranoid threat is sometimes hard to detect in the clinical interview, a simple bedside test to identify patients suffering from paranoid experience was recently proposed: the interpersonal distance test.

Methods

For measuring interpersonal distance in patients with schizophrenia and age-, gender- and education-matched healthy controls, we performed a stop-distance paradigm. To accomplish the paradigm, we positioned experimenter and participant at opposite ends of the room with a distance of seven meters facing each other. The stop-distance paradigm contained four different conditions; two active conditions (i.e. participant is approaching experimenter) and two passive conditions (i.e. experimenter is approaching participant) both, with and without eye contact. Participants were instructed to stop or tell the experimenter to stop at a distance, at which they would start to feel less comfortable. Moreover, we assessed paranoid threat with the Bern Psychopathology Scale. We compared the interpersonal distance between patients with current experiences of paranoid threat, schizophrenic patients without paranoia and healthy controls.

Results

Patients with higher ratings in paranoid experience presented with higher interpersonal distance than patients without paranoid threat and matched healthy controls. This effect was most prominent in the passive conditions. Patients without paranoia did not differ from healthy controls in the interpersonal distance test.

Discussion

Interpersonal distance is a reliable indicator of current paranoid threat in patients with schizophrenia. In fact, interpersonal distance is not generally altered in schizophrenia. However, paranoid threat leads to impairments in interpersonal space regulation. This is of particular relevance as interpersonal distance might be predictive of social and functional outcome and aggressive behaviour in schizophrenia.
M31. THE ASSOCIATION BETWEEN BULLYING VICTIMIZATION AND PSYCHOSIS AND THE MEDIATING ROLE OF PEER AND FAMILY SOCIAL SUPPORT
Authors: Shannon Ciaran , Jordan Julie-Ann , Higgins Kathryn , Kelly Grace , Mulholland Ciaran
Published: May 2020

Background

The relationship between psychotic symptoms and bullying has received limited attention to date. A systematic review by Cunningham, Hoy, & Shannon (2016) identified only ten studies that met their inclusion criteria for examining the relationship between childhood bullying and psychosis via a prospective research design. A meta-analysis of these studies suggested that being bullied does predict the later development of psychotic symptoms. The authors went on to say that a better understanding of the factors that mediate the bullying/psychosis relationship is needed. It is possible that prolonged exposure to social adversity and exclusion can lead to a state of “social defeat” which has also been found to increase the risk of psychosis (Johnston et al., 2011; Selten et al., 2013; Selten and Cantor-Graae, 2005). Being bullied in childhood has also been linked to depression in adulthood (Bowes et al. 2014), and social support from family and friends may also mediate the bullying victimisation-depression relationship.

Methods

The present study is a secondary data analysis of a prospective cohort study; namely, the Belfast Youth Development Study (BYDS). The BYDS followed a group of children longitudinally from ages 12–21 years. The participants are 2,087 individuals who took part in the Belfast Youth Development Study (BYDS) in 2011 (Wave 7). This longitudinal survey started in 2001 (Wave 1) when the sample members were aged 11 years. The sample were then surveyed again annually up until age 15 years (Waves 2–5), and post-compulsory schooling follow ups were carried out at 17 and 21 years (Waves 6 & 7). The secondary analysis will involve conducting path models. The first of which will be a bullying victimisation-psychosis mediation model; this will include a predictor (bullied, age 12 years), outcome (Psychosis, age 21 years), mediators (e.g. peer attachment, age 13 years; parental attachment. age 14 years), and covariates (gender, free school meals, depression, and frequency of cannabis use in the past year; cannabis abuse screening test). A bullying victimisation-depression mediation model will also be examined; this will include the same mediator and covariate variables.

Results

The results will be reported in the poster submission (analysis in progress). These will include measures of direct and indirect effect, as well as model fit statistics.

Discussion

Clinical implications in terms of prevention, assessment, and intervention for young people at risk of psychotic disorders will be discussed.
M42. INDEPENDENT REVIEW & MONITORING IMPROVES QUALITY OF PANSS DATA IN GLOBAL CLINICAL TRIALS
Authors: Echevarria Barbara , Liu Cong , Negash Selam , Opler Mark , Molero Patricio , Capodilupo Gianna
Published: May 2020

Background

The Positive and Negative Syndrome Scale (PANSS) (1) is the most widely used endpoint for measuring change in schizophrenia clinical trials. A set of flags have been developed by ISCTM expert working group to identify potential scoring errors in PANSS assessments (2). Measures have been taken by sponsors (pharmaceutical industry) with the goal of increasing scoring reliability and data quality, such as the use of Independent Review (IRev). We evaluated changes in data quality when site raters stop being recorded and monitored via IRev by comparing two studies with the same cohort of raters, one with independent review and one without.

Methods

Data from PANSS assessments in two global multisite schizophrenia clinical trials were analyzed. We selected data from raters participating in both studies (which run concurrently for a significant period of time). Raters were rigorously trained on administration and scoring conventions and certified prior to the study through demonstration of adequate interrater reliability. In addition to these steps, raters in study A were required to audio record all PANSS assessments with a selected subset of visits being subject to IRev. PANSS assessments in study B were neither recorded nor monitored via IRev. Data quality after study completion was examined by calculating the frequency of anomalous data patterns identified as “high” (very probable or definite error) by the ISCTM Working Group in both studies. Additionally, we examined the percentage of assessments with lower than expected PANSS interview duration as captured via an eCOA platform.

Results

There were 9441 eCOA PANSS assessments in study A and 6178 in study B included in this analysis. The proportions of flags that represented highly probable/definite error differed significantly between the studies (9% vs 18% for Study A and B, respectively, p<.01). The most significant differences in ISCTM flags were related to overly consistent scoring patterns (27 or more items scored identically to the prior visit) occurring with higher frequency in study B. Additionally, study B also had a significantly higher frequency of assessments flagged for low interview duration (< 15 minutes) (1% vs 4% for Study A and B, respectively, p<.01).

Discussion

Initial rater training is necessary but not sufficient to ensure adequate data quality in schizophrenia trials. Implementation of additional in-study oversight through Independent Review or similar methods reduces the probability of data error in PANSS assessments, including the appearance of improbable rating patterns and decreased time spent interviewing study subjects. One potential limitation is that study A is a double-blind study whereas study B is an open label extension of study A.