bluuebunny/crossref_metadata_2025 huggingface dataset:
Collateral Toxicity Limits the Evolution of Bacterial Release Factor 2 toward Total Omnipotence
Authors: Abdalaal Hind , Pundir Shreya , Ge Xueliang , Sanyal Suparna , Näsvall Joakim
Published: May 2020

When new genes evolve through modification of existing genes, there are often tradeoffs between the new and original functions, making gene duplication and amplification necessary to buffer deleterious effects on the original function. We have used experimental evolution of a bacterial strain lacking peptide release factor 1 (RF1) in order to study how peptide release factor 2 (RF2) evolves to compensate the loss of RF1. As expected, amplification of the RF2-encoding gene prfB to high copy number was a rapid initial response, followed by the appearance of mutations in RF2 and other components of the translation machinery. Characterization of the evolved RF2 variants by their effects on bacterial growth rate, reporter gene expression, and in vitro translation termination reveals a complex picture of reduced discrimination between the cognate and near-cognate stop codons and highlights a functional tradeoff that we term “collateral toxicity.” We suggest that this type of tradeoff may be a more serious obstacle in new gene evolution than the more commonly discussed evolutionary tradeoffs between “old” and “new” functions of a gene, as it cannot be overcome by gene copy number changes. Further, we suggest a model for how RF2 autoregulation responds to alterations in the demand not only for RF2 activity but also for RF1 activity.
Integrating NMR and simulations reveals motions in the UUCG tetraloop
Authors: Bottaro Sandro , Nichols Parker J , Vögeli Beat , Parrinello Michele , Lindorff-Larsen Kresten
Published: May 2020

We provide an atomic-level description of the structure and dynamics of the UUCG RNA stem–loop by combining molecular dynamics simulations with experimental data. The integration of simulations with exact nuclear Overhauser enhancements data allowed us to characterize two distinct states of this molecule. The most stable conformation corresponds to the consensus three-dimensional structure. The second state is characterized by the absence of the peculiar non-Watson–Crick interactions in the loop region. By using machine learning techniques we identify a set of experimental measurements that are most sensitive to the presence of non-native states. We find that although our MD ensemble, as well as the consensus UUCG tetraloop structures, are in good agreement with experiments, there are remaining discrepancies. Together, our results show that (i) the MD simulation overstabilize a non-native loop conformation, (ii) eNOE data support its presence with a population of ≈10% and (iii) the structural interpretation of experimental data for dynamic RNAs is highly complex, even for a simple model system such as the UUCG tetraloop.
Identification of gene fusion events in Mycobacterium tuberculosis that encode chimeric proteins
Authors: Gallant James , Mouton Jomien , Ummels Roy , ten Hagen-Jongman Corinne , Kriel Nastassja , Pain Arnab , Warren Robin M , Bitter Wilbert , Heunis Tiaan , Sampson Samantha L
Published: May 2020

Mycobacterium tuberculosis is a facultative intracellular pathogen responsible for causing tuberculosis. The harsh environment in which M. tuberculosis survives requires this pathogen to continuously adapt in order to maintain an evolutionary advantage. However, the apparent absence of horizontal gene transfer in M. tuberculosis imposes restrictions in the ways by which evolution can occur. Large-scale changes in the genome can be introduced through genome reduction, recombination events and structural variation. Here, we identify a functional chimeric protein in the ppe38–71 locus, the absence of which is known to have an impact on protein secretion and virulence. To examine whether this approach was used more often by this pathogen, we further develop software that detects potential gene fusion events from multigene deletions using whole genome sequencing data. With this software we could identify a number of other putative gene fusion events within the genomes of M. tuberculosis isolates. We were able to demonstrate the expression of one of these gene fusions at the protein level using mass spectrometry. Therefore, gene fusions may provide an additional means of evolution for M. tuberculosis in its natural environment whereby novel chimeric proteins and functions can arise.
O4.5. LONG TERM EFFECTS OF EARLY INTERVENTION SERVICES FOR FIRST EPISODE PSYCHOSIS: OUTCOMES OVER FIVE YEARS FROM THE RECOVERY AFTER A 1ST EPISODE OF SCHIZOPHRENIA-EARLY TREATMENT PROGRAM (RAISE-ETP)
Authors: Robinson Delbert , Schooler Nina , Kane John
Published: May 2020

Background

Early intervention services (EIS) for first episode psychosis (FEP) are now implemented worldwide and these integrated and team-based treatment programs improve FEP outcomes while patients are participating. EIS service and treatment models provide care for limited periods followed by return to standard services. Cross sectional follow-up studies conducted after EIS participation ends have not been able to find advantages compared with standard care. The RAISE-ETP study was the first US-based, multi-center randomized clinical trial to compare an EIS, labeled NAVIGATE, to usual clinical care. Those who received NAVIGATE experienced significant improvement in symptoms and functioning compared to those who received usual care during the initial two-year treatment period. We now report clinical outcomes covering five years, a time frame that includes care after EIS participation ended.

Methods

RAISE-ETP was a cluster randomized clinical trial conducted at 34 US sites; 17 sites provided NAVIGATE to 223 participants and 17 sites provided usual clinical care to 181 participants. NAVIGATE was available until the last randomized subject had the opportunity for two years of services. Participants were assessed every six months for up to 60 months by masked, centralized assessors utilizing live two-way video and with the Heinrichs-Carpenter Quality of Life Scale (QLS) and the Positive and Negative Syndrome Scale (PANSS).

Results

Participants had a mean age of 23 years and the majority were male; (78% in NAVIGATE and 66% in usual care). The mean opportunity for NAVIGATE treatment was 33.8 (SD=5.1) months; the longest 44.4 months. Compared with usual care, NAVIGATE over 5 years was associated with a 13.14 unit QLS (p<0.001) and 7.73 unit PANSS (p<0.002) better improvement and 2.5 fewer inpatient days (p=0.02). NAVIGATE opportunity length did not affect QLS outcome; duration of untreated psychosis did not moderate differential QLS outcome.

Discussion

RAISE-ETP provides compelling evidence of a substantial long-term benefit for FEP treatment with the NAVIGATE EIS compared with standard care.
O5.2. CBD MODULATION OF HIPPOCAMPAL GLUTAMATE IN PSYCHOSIS
Authors: O’Neill Aisling , Annibale Luciano , Blest-Hopley Grace , Wilson Robin , Bhattacharyya Sagnik
Published: May 2020

Background

Emerging evidence supports the antipsychotic effect of cannabidiol (CBD), a non-intoxicating component of cannabis, in people with psychosis. However, how CBD might exert its antipsychotic effect remains unclear. While current antipsychotic medications typically target the dopaminergic neurotransmitter system, preclinical findings suggest that CBD may directly or indirectly affect multiple distinct modes of neural signalling, including both glutamate and dopamine. However, no study has as yet investigated the effect of CBD on brain glutamate levels in patients with psychosis as a potential mechanism underlying its antipsychotic effects.

Methods

We investigated the effects of a single oral dose of CBD (600mg), compared to a matched placebo, in patients within 5 years of onset of psychosis, using a double-blind, randomized, placebo-controlled, repeated-measures, within-subject cross-over design, with at least a one-week interval between scans to allow washout of CBD. After drug administration, 13 patients (mean age 27.73, 66.7% male) were scanned using proton magnetic resonance spectroscopy to measure left hippocampal glutamate levels. Symptom severity was assessed using the Positive and Negative syndrome scale (PANSS) 60mins before drug administration (T1, pre scan), and 270mins after drug administration (T2, post scan). Effects of CBD on left hippocampal glutamate levels, symptoms, and correlations between hippocampal glutamate and symptoms were investigated.

Results

Compared to placebo, there was a significant increase in left hippocampal glutamate in the psychosis patients under CBD treatment (z= -1.80; p=0.035). Under placebo treatment, change in positive psychotic symptoms (as indexed using the T1 minus T2 PANSS positive symptoms subscale scores) was directly correlated with left hippocampal glutamate levels (rho= 0.69, p=0.004), such that symptoms increased as hippocampal glutamate levels decreased. This significant relationship was not observed under the CBD treatment (rho= 0.102, p=0.72).

Discussion

This suggests that positive psychotic symptoms may be driven by abnormal hippocampal glutamate concentration, which is sensitive to modulation by CBD. These findings are in keeping with the purported antipsychotic effects of CBD in psychosis, and provide novel insight into the neurochemical interactions underlying these effects.
T34. THE IMPACT OF ANTIDEPRESSANT USE ON THE TRANSITION TO PSYCHOSIS RATE IN THE NEURAPRO TRIAL
Authors: Schlögelhofer Monika , McGorry Patrick D , Nelson Barnaby , Berger Maximus , Markulev Connie , Pan Yuen Hok , Schäfer Miriam R , Mossaheb Nilufar , Smesny Stefan , Hickie Ian B , Berger Gregor , Chen Eric Y H , De Haan Lieuwe , Nieman Dorien , Nordentoft Merete , Riecher-Rössler Anita , Verma Swapna , Thompson Andrew , Yung Alison , Amminger G Paul
Published: May 2020

Background

Over the last two decades, several randomised controlled trials (RCTs) have indicated that preventive psychosocial, pharmacologic (Van der Gaag et al. 2013), and nutritional interventions (Amminger et al. 2010) are likely to be beneficial in people at ultra-high risk (UHR) of psychosis, in terms of delaying or preventing a transition to psychosis. Antidepressant medication is commonly prescribed in young people at UHR for psychosis; however, the evidence regarding its efficacy for psychosis prevention is limited (Fusar-Poli et al. 2007; Cornblatt et al. 2007; Fusar-Poli et al. 2015). The main aim of the present study is to investigate the impact of concomitant AD medication on the transition to psychosis rate in young people at ultra-high risk of psychosis who participated in the NEURAPRO trial (McGorry et al. 2017).

Methods

In this secondary analysis, data from 304 participants of a multicenter, double-blind, placebo-controlled, randomized clinical trial (NEURAPRO) of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) were included. During the trial, concomitant antidepressant medication was permitted for treatment of moderate to severe major depressive disorder (a score of ≥ 21 on the Montgomery-Asberg Depression Rating Scale, MADRS) in all participants.

Results

Of 304 participants, 189 (62.2%) were treated with ADs. 98 (64.1%) of those were in the omega-3 group and 91 (60.3%) in the placebo group. The transition rate to psychosis was higher in individuals who received AD treatment (13.2%; 25 of 189) as in individuals without ADs (6.1%; 7 of 115). The Kaplan-Meier survival curve estimated a group difference of X2 = 3.237, P = .072 (log rank test).

Discussion

Antidepressants are widely used in early psychosis. This analysis does not support the view that antidepressants may have reduced the transition to psychosis rate in this cohort. The findings are limited by the fact that antidepressants were prescribed based on clinical discretion. A randomised controlled trial is needed to determine whether antidepressants have a role in prevention of transition to psychosis.
T36. NEURAL CHANGES FOLLOWING A BODY-ORIENTED RESILIENCE THERAPY WITH ELEMENTS OF KICKBOXING FOR INDIVIDUALS WITH A PSYCHOTIC DISORDER: A RANDOMIZED CONTROLLED TRIAL
Authors: van der Stouwe Elisabeth , Pijnenborg Marieke (Gerdina) , Opmeer Esther , de Vries Bertine , Bernard Marsman Jan , Aleman Andre , van Busschbach Jooske
Published: May 2020

Background

Individuals with a psychotic disorder are at an increased risk of becoming the victim of a crime. A body-oriented resilience therapy with elements of kickboxing (‘BEATVIC’) aimed at preventing victimization by addressing putatively underlying factors was developed. One of these factors is social cognition, particularly facial affect processing. The current study investigated neural effects of BEATVIC using two face processing tasks.

Methods

Participants were randomized to either BEATVIC or a ‘Befriending’ control group consisting of social group meetings. Twenty-seven patients (BEATVIC n=14; Befriending n=13) completed an Emotional Faces task and the Wall of Faces task during fMRI, pre and post intervention. General linear model (GLM) analyses and Independent component analyses (ICA) were performed to define networks and investigate group*time effects.

Results

Voxelwise GLM analyses yielded no differences between groups over time. On a network level (ICA) we found overall increased activation of the salience network to angry and fearful faces in BEATVIC compared to Befriending. A trend towards significance (p=0.05) for increased activation of the (medial) visual network to (a group of predominantly) angry faces, and decreased deactivation (p=0.08) in the sensorimotor network in response to fearful faces in BEATVIC was observed.

Discussion

Increased activation of the salience network may suggest an increased alertness for potentially dangerous faces. Trend findings of the visual network and the sensorimotor network which are formally statistically insignificant may be regarded as tentative and strongly warrant further investigation to allow for more definite conclusions. Increased activation of the visual network might suggest more elaborate processing of visual information. Decreased deactivation in the sensorimotor network might indicate a reduced tendency for “freezing” and enhanced action readiness in response to indirect threat.
T40. GLYCERYL TRINITRATE IN FIRST EPISODE PSYCHOSIS UNMEDICATED WITH ANTIPSYCHOTICS: A RANDOMISED CONTROLLED FEASIBILITY STUDY
Authors: Merritt Kate , Catalan Ana , Cowley Samuel , Demjaha Arsime , Taylor Matthew , McGuire Philip , Cooper Ruth , Morrison Paul
Published: May 2020

Background

There is a pressing need for new classes of treatment for psychosis. A key therapeutic target for novel compounds is the NMDA receptor, which may be modulated by nitric oxide donors such as sodium nitroprusside (SNP). Recent early phase studies of SNP in patients with psychosis have had mixed results, and the drug has to be administered intravenously. GTN is a well-established cardiovascular medicine that is also a nitric oxide donor, and can be given orally. We explored the safety and effectiveness of GTN in unmedicated patients with a first episode of psychosis.

Methods

A single-centre, randomized, double-blind, placebo-controlled trial was conducted from December 2016 to April 2019 (ClinicalTrials.gov identifier: NCT02906553). Patients with a first episode of psychosis were recruited from the South London and Maudsley NHS Trust, London, UK. Nineteen patients were randomised to receive 3 x sprays of GTN or placebo for 3 consecutive days, and re-assessed on Day 7. Thirteen participants were included in the final analyses. At each assessment point, symptom levels were measured using the Positive and Negative Syndrome Scale (PANSS), and cognitive performance was evaluated using the Jumping to Conclusions (JTC) and the Hopkins Verbal Learning (HVLT) tasks.

Results

Compared to placebo, GTN was well tolerated, but it was not associated with significant effects on either psychotic symptoms or cognition. Bayesian statistics indicated with moderate confidence that GTN does not have a therapeutic effect.

Discussion

This study indicates that nitric oxide donors are not therapeutically beneficial in psychosis. It also highlights the difficulties in recruiting unmedicated patients with psychosis. Future clinical trials would benefit from frameworks built into clinical services, to signpost patients not responding to medication and those discontinuing medication to clinical trials of alternatives.
T85. LIVING WITH PSYCHOSIS IN LATER LIFE
Authors: Galletly Cherrie , Suetani Shuichi , McKellar Duncan , Castle David J
Published: May 2020

Background

Whilst there is considerable focus on early intervention for young people with psychotic disorders, there is little research looking at older people. Although some of these individuals have a recent onset, most will have been living with psychosis for many years. The older population has increased risks of cardiometabolic complications and this is likely to be complicated by psychosis.

Methods

The Australian Survey of People Living with Psychosis included 1478 participants aged 18–49 years, and 346 participants aged 50–64 years. The two groups were compared across a range of demographic, diagnostic, physical health, substance abuse and lifestyle factors.

Results

The older group contained significantly more women (48.3% vs 38.6%, p<0.0001). There was a smaller proportion of people with ICD-10 schizophrenia (36.1% vs 45.4% p<0.012), and higher proportions with schizoaffective disorder and affective psychoses. Significantly fewer of the older participants were prescribed clozapine (11.0% vs 16.8%, p < 0.0001). The mean age of onset was later in the older group (30.05 vs 22.23 years, p < 0.0001).

There was a striking difference in rates of drug and alcohol abuse. The older group had lower rates of hazardous, harmful or dependent drinking (15.3% vs 35.9%, p < 0.0001), lifetime cannabis use (35.6% vs 74.1%, p < 0.0001), past year cannabis use (11.1% vs 38.1%, p < 0.0001), lifetime amphetamine use (12.8% vs 47.0%, p < 0.0001), and past year amphetamine use (2.9% vs 14.9%, p < 0.0001). The older group were also less likely to currently smoke tobacco (56.9% vs 68.9%, p < 0.0001).

Older people were more likely to live alone (45.1% vs 28.6%, p < 0.000). They were less likely to experience food poverty; in the last year 19.5% of older people and 30.7% of younger people had run out of food and did not have money to buy more.

Cognitive function was poorer with slower processing speed in the older group, with the NART error score indicating premorbid intelligence was lower in the older group.

Older people were more likely to be overweight or obese (80.6% vs 74.3%, p < 0.0001), as well as being more likely to have metabolic syndrome (56.1% vs 48.5%, p = 0.034). There was a greater proportion with very low exercise in the older group (41.6% vs 31.7% p = 0.003).

Discussion

Older people with psychosis are more likely to be female and more likely to be diagnosed with an affective psychosis. The poorer cognitive function and higher rates of obesity and metabolic syndrome are consistent with changes seen in aging in the normal population. The older group have much lower rates of both lifetime and current drug and alcohol abuse, and smoking. Whilst there is considerable attention to cardiovascular health as a determinant of premature mortality, our results suggest that lifetime alcohol, cannabis and amphetamine use may also be associated with failure to survive into older age.
T232. PREMORBID SOCIAL FUNTIONING AND AFFECTIVE SYMTPOMS ARE RELATED TO SUBJECTIVE OUTCOME AMONG OUTPATIENTS WITH SCHIZOPHRENIA
Authors: Hörtnagl Christine , Frajo-Apor Beatrice , Yalcin-Siedentopf Nursen , Kemmler Georg , Biedermann Falko , Hofer Alex
Published: May 2020

Background

Improving the subjective outcome of patients should be an important target in the treatment of schizophrenia. Accordingly, the aim of the present study was to examine the influence of determining factors, namely premorbid functioning, residual symptoms, and side effects of antipsychotic medication on subjective outcome.

Methods

70 outpatients with schizophrenia (ICD-10) who were clinically stable for a period of at least six months were included into a cross-sectional study. Premorbid functioning, psychopathology, and side effects were assessed by using the Premorbid Adjustment Scale, the Positive and Negative Syndrome Scale, and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale, respectively. Subjective outcome was measured in terms of life satisfaction (Life Satisfaction Questionnaire, LSQ), self-esteem (Index of Self-Esteem, ISE), and needs for care (Berliner Bedürfnisinventar, BeBI).

Results

Both premorbid social functioning and affective symptoms correlated negatively with most life domains assessed by the LSQ as well as with self-esteem and were associated with less health, social, and functional needs. Concerning side effects, parkinsonism and akathisia showed a significant negative correlation with self-esteem.

Discussion

Our results highlight the complex nature of subjective outcome in patients suffering from schizophrenia. Evidently, premorbid social functioning plays a prominent role in the experienced subjective outcome in the course of the illness. Furthermore, our findings underscore that constant efforts are essential to reduce depressive symptoms or anxiety in patients. Special attention should also be paid to extrapyramidal motor side effects of medication.
M15. MORPHOLOGY OF THE SUPERIOR TEMPORAL SULCUS IN PATIENTS WITH SCHIZOPHRENIA: A MARKER OF GENETIC OR ENVIRONMENTAL VULNERABILITY?
Authors: Lerosier Baptiste , Dollfus Sonia , Takerkart Sylvain , Auzias Guillaume , Etard Olivier , Simon Gregory
Published: May 2020

Background

Hallucinations are the most common and debilitating symptom in schizophrenia, affecting more than 70% of patients. The superior temporal sulcus (STS) is involved in the language process notably in the perception of the human voice and several studies show its implication in auditory verbal hallucinations (AVHs). Sulcal patterns in the white matter can reflect an early vulnerability, probably genetic since they set up at a very early stage and are stable over the life course. In contrast, the cortical thickness is dynamic and variable over the development and so can reflect the impact of environmental factors on the maturation of the brain. The aim of this study is therefore to determine whether AVHs are associated with morphological changes of the STS and in particular, whether these changes concern sulcal patterns or cortical thickness reflecting early (genetic) or late (environmental) vulnerability respectively.

Methods

Seventy-three schizophrenia patients (DSM-IV) with a proneness of AVH (53 AVH+) and without AVH (20 AVH-) and 100 healthy volunteers (HC) had a 3T MRI brain scan. Cortical reconstructions were generated using Freesurfer. Mean cortical thickness was measured over the entire brain in each participant. Number of sulcal pits, which represents the position with the maximum depth in the sulcus, was automatically counted on the white matter surface. Both measures were compared between groups and related to the Auditory Hallucination Rating Scale (AHRS).

Results

AVH+ patients compared to HC showed a significantly thinner cortical thickness in the left temporal and frontal regions and especially in the STS (p ≤ 0.05 FDR corrected). A negative correlation (r²=0.25) between the cortical thickness in the central part of the left STS and the AHRS score was found (p = 0.01 uncorrected). A different distribution of the number of pits in the left STS is found in AVH+ patients compared to HC (p = 0.05).

Discussion

The results suggest that AVH+ patients compared to HC have a lower cortical thickness in the left STS, but also have a specific white matter pattern of the left STS. These results support the hypothesis that a particular morphology of the STS related with auditory hallucinations might be due to both early (genetic) and late (environmental) factors.
M61. THE ROLE OF PERSONAL WORLDVIEW IN PREDICTING DELUSION PRONENESS IN A NON-CLINICAL SAMPLE
Authors: Zamperoni Georgia , Tan Eric , Neill Erica , Rossell Susan , Tan Eric
Published: May 2020

Background

Unusual thought processes, often referred to as delusion proneness, are not unique to clinical populations. Understanding the factors that contribute to delusion proneness has important theoretical and clinical implications in prodromal psychosis.

Methods

This study ascertained the presence of delusion proneness and associated levels of distress, preoccupation and conviction in a large sample of healthy participants (N=258, M= 33.62 years, SD =12.04), and subsequently investigated two aspects of personal worldview in predicting delusion proneness: Locus of control (LOC) and core positive and negative schemas of the self and others. This data was collected via an online survey.

Results

Stepwise regression analyses indicated that negative schemas of others predicted the presence of delusion proneness (p<.001) and associated levels of distress (p= .012) and preoccupation (p= .025); whilst negative schemas of the self predicted only the presence of delusion proneness (p= .001). Hierarchical regression analysis demonstrated that LOC was not a significant predictor of the presence of delusion proneness (p= .141), or associated features of distress (p =.281), preoccupation (p=.220) and conviction (p= .660).

Discussion

The current study found that negative schemas of others accounted for more variance in predicting delusion proneness and aspects of experience (distress and preoccupation) than negative self- schemas. Our study may suggest that therapy focusing on one’s regulation of emotions and assumptions about others in individuals with delusion-like beliefs may be more critical in alleviating delusional symptoms than exclusively focusing on self-schemas.
M67. UNDERSTANDING SOCIAL COGNITION IN SCHIZOPHRENIA THROUGH THE LENS OF SCHIZOTYPY
Authors: Lee Sara-Ann , Lim Keane , Lam Max , Lee Jimmy
Published: May 2020

Background

Social cognitive deficits are common, detectable across a wide range of tasks and appear to play a key role in influencing poor functioning in schizophrenia. Despite its importance as a treatment target, the factors that underlie social cognitive deficits in schizophrenia remains elusive. Schizotypy appears to be one such factor that can explain the variability in social cognitive deficits seen in schizophrenia. The study’s primary aim was to provide a more comprehensive understanding of social cognitive functioning and its relationship to schizotypy.

Methods

108 patients and 70 healthy controls completed nine tasks across 4 social cognitive domains based on the SCOPE study. In addition, all participants completed the Schizotypal Personality Questionnaire. Clinical symptoms were also rated using the Brief Psychiatric Rating Scale.

Results

Theory of Mind, social perception, emotion processing and attribution bias were measured in patients with schizophrenia (n = 108) and healthy controls (n = 70). A social cognition composite score was calculated using principal components analysis. Cluster analysis on the derived factor scores revealed 3 clusters. Multiple univariate ANOVAS with Bonferroni correction were used to examine differences between the 3 clusters on each of the 4 social cognition domain scores, which indicated that higher social cognitive performance was related to lower schizotypy. In addition, results indicated that despite differences in the social cognitive performance among patients in the 3 clusters, they did not differ in clinical outcome measures.

Discussion

The primary aim of the study was to address gaps in the current literature by examining the relationship between social cognition and schizotypy. This study built upon past studies which had the tendency to focus on single, discrete domains by comparing the social cognitive performance of patients and controls using an extensive battery of tests, indexing four social cognitive domains. The significant differences on total SPQ score and the SPQ domain scores between the various clusters, coupled with the significant correlations between schizotypy and social cognition, reinforces the utility of schizotypy in refining our understanding of the variation in the degree of social cognitive deficits in schizophrenia. In conclusion, this study substantiates the importance of understanding the relationship between social cognition and schizotypy. This could support and pave the way for the development and implementation of targeted social cognitive interventions catered to the patients’ level of deficit.
M69. IMPROVING VISUAL ATTENTION TO SOCIAL STIMULI IN INDIVIDUALS WITH SCHIZOPHRENIA
Authors: Klein Hans , Pinkham Amy
Published: May 2020

Background

Social dysfunction is a hallmark characteristic of schizophrenia, and individuals with this disorder often report difficulty navigating daily social interactions. Perceptual deficits, such as faulty visual attention to important aspects of social stimuli (i.e., failing to look at the most relevant portions of a stimulus), may be one mechanism by which social deficits arise. Faulty modulation of specific neural regions such as the right temporoparietal junction (rTPJ), may underlie visual attention abnormalities, and may act as suitable targets for neurostimulation. The current study utilizes neurostimulation to experimentally manipulate specific neural networks and determine whether stimulation 1) improves visual attention, 2) improves performance on social cognitive tasks, and 3) whether altered visual attention moderates this improved performance.

Methods

Using a double-blind crossover design, participants underwent both active and sham stimulation via tDCS approximately one week apart. Half of the participants received active and sham stimulation of rTPJ (n = 22), while the other half received active and sham stimulation of a comparator site within the social brain network (dmPFC, n = 23). After stimulation, visual attention was assessed through concurrent eye-tracking while participants complete several tasks of social cognition (emotion recognition: ER40, BLERT; Theory of Mind: TASIT). Visual attention was determined as the proportion of time spent attending to socially and contextually important AOIs.

Results

Data collection and data processing are still ongoing for this study, however planned interim analyses on a subset of the total sample (n = 45) indicate small to medium effects of active stimulation to the rTPJ compared to sham and dmPFC stimulation for both visual attention (ηp2=.035) and social cognitive performance on the BLERT task (ηp2=.067), specifically. These same effects are not seen in the other social cognitive tasks. Final analyses based on a sample size of 72 individuals are expected to be complete prior to presentation at SIRS 2020.

Discussion

This study is the first, to our knowledge, to target this neural region within schizophrenia for the purposes of improving visual attention and, subsequently, social cognition. Should the pattern of results from our interim analyses hold after completion of data collection, results indicate that active stimulation to the rTPJ has a unique impact on dynamic emotional stimuli, improving visual attention and accuracy in emotion recognition, suggesting a primary role of the rTPJ and visual attention in performance on this task. The intricate design of this study allows for thorough investigation of potential mechanisms by which social cognitive deficits develop, and the use of novel experimental techniques align with the theme of this year’s conference.
M83. AUTISTIC TRAITS AS LINKING PIN TO SOCIAL FUNCTIONING IN PSYCHOSIS: A NETWORK APPROACH
Authors: Ziermans Tim , Isvoranu Adela-Maria , Schirmbeck Frederike , Geurts Hilde , De Haan Lieuwe ,   GROUP Investigators
Published: May 2020

Background

Both psychotic and autistic traits are related to poor social outcome in individuals with psychotic disorders (PD). However, it is unknown how specific trait clusters relate to each other and which are pivotal to social functioning. The aim of the present study was to use a network approach to address this issue and to investigate whether relations are similar in individuals with a familial risk for psychosis (FR) or typical comparisons (TC).

Methods

The total sample consisted of 1413 individuals (504 PD, 572 FR, and 337 TC). Traits were assessed with the Autism Spectrum Quotient (AQ; 5 nodes) and the Community Assessment of Psychic Experiences (CAPE; 9 nodes). Social functioning was measured with the Social Functioning Scale (7 nodes).

Results

Overall our results show that autistic traits are more negatively and closely related to social functioning, particularly in the interpersonal environment, than psychotic traits. These relations are more intrinsically connected for the PD network, as more and stronger connections between nodes were observed than for the FR and TC networks. In addition, the latter two networks appeared strikingly similar with only few unique relations.

Discussion

Presence of autistic traits generally have a negative effect on social functioning, but in PD they may have a disproportional detrimental effect on psychopathology and levels of social functioning. These findings emphasize the need for increased clinical awareness of autistic comorbidity in psychotic patients to help enrich their daily social environments.
M233. EXPERIENTIAL NEGATIVE SYMPTOMS ARE MORE PREDICTIVE OF REAL-LIFE FUNCTIONAL OUTCOME THAN EXPRESSIVE NEGATIVE SYMPTOMS IN CLINICAL HIGH-RISK STATES
Authors: Birkedal Glenthoej Louise , Dam Kristensen Tina , Wenneberg Christina , Hjorthøj Carsten , Nordentoft Merete
Published: May 2020

Background

Negative symptoms are key features of schizophrenia spectrum disorders that are linked to psychosis development and functional impairments. This study investigated the predictive power of negative symptoms domains on multiple aspects of real-life functional outcome in individuals at Ultra High-Risk (UHR) for psychosis.

Methods

A total of 146 UHR individuals were enrolled in a randomised, clinical trial. This study reports on analyses secondary to the RCT. The UHR individuals were assessed at baseline with the Scale for the Assessment of Negative Symptoms (SANS) encompassing the four domains of affect, alogia, avolition, and anhedonia. Functioning measures, comprising overall-, social-, and role functioning, self-report social functioning, and quality of life, were obtained at 12-month follow-up. Regression analyses elucidated on the relationship between the four negative symptom domains and functional outcomes.

Results

The aspects of negative symptoms most predictive of real-life functioning at 12-month follow-up were anhedonia and avolition explaining 6–19% of the variance on the functional outcome measures. The finding was maintained when controlling for the effect of neurocognition, antipsychotic medication, and depressive symptoms.

Discussion

Our study finds experiential negative symptoms to predict multiple areas of real-life functioning and quality of life, while expressive negative symptoms exert a modest influence on the functional prognosis of UHR individuals. Hence, experiential negative symptoms (such as motivational deficits and asociality) may constitute an important treatment target in intervention approaches aimed at enhancing the functional outcome of UHR individuals.
S33. RELATIVES IN RESOURCE GROUP ASSERTIVE COMMUNITY TREATMENT (RACT): RELATIVES’ EXPERIENCES
Authors: Sjöström Nils , Ewertzon Mats , Johansson Ola , Weimand Bente , Johansson Anita , Mellgren Zophia , Ek-Persson Jane , Waern Margda
Published: May 2020

Background

Relatives often provide extensive support to their next of kin suffering from psychotic disorders. However, they often experience lack of support from psychiatric services. While cooperation with relatives is a central component in Resource Group Assertive Community Treatment (RACT), little is known about relatives’ experiences of RACT. The aim was to investigate relatives’ experiences of encountering psychiatric care with and without RACT, in relation to quality of life, family burden and family stigma.

Methods

A total of 139 relatives of individuals suffering from psychotic disorders in the Region Västra Götaland, Sweden filled out the self-report instruments Family Involvement and Alienation Questionnaire – Revised (FIAQ-R), the Burden Inventory for Relatives of Persons with Psychotic Disturbances, the Inventory of Stigmatizing Experiences (family version), and RAND-36.

Results

Participants included 79 relatives with experience of RACT and 60 without. In the total group 70% were women. Mean age was 63 years (SD 12.4). A majority came from Sweden (91%), had >12 years of education (61%) and did not live together with the patient (76%). A majority were parents, (70%). These demographic characteristics did not differ in those with and without RACT. We found that relatives who participated RACT experienced a more positive approach from the healthcare professionals compared to those without RACT (p=.001). Furthermore, relatives who participated in RACT felt to a lower extent that they were alienated from the provision of care than did other relatives (p=.005). Relatives who did not participate in resource group were significantly more afraid that their ill next of kin would hurt someone. The association remained after adjustment for experience of approach and feeling of alienation. No other differences in family burden variables were found. Findings regarding mental Quality of Life scores and experiences of family stigmatization were similar in those both with and without RACT.

Discussion

The results suggest that participating in RACT may contribute to a higher level of satisfaction for relatives in their encounter with healthcare professionals.
S34. EFFECTIVENESS OF INDIVIDUAL METACOGNITIVE TRAINING (MCT+) IN FIRST-EPISODE PSYCHOSIS
Authors: Ochoa Susana , Lopez-Carrilero Raquel , Luisa Barrigon Maria , Pousa Esther , Grasa Eva , González Fermin , Monserrat Clara , Gutierrez-Zotes alfonso , Lorente Esther , Barajas Ana , Ruiz-Delgado Isabel , Cid Jordi , Birules Irene , Pélaez Trinidad , García-Mieres Helena , Vila-Badia Regina , Moritz Steffen ,   Spanish Metacognition Group
Published: May 2020

Background

The individual Metacognitive Training (MCT+) is useful to reduce positive symptoms in people with schizophrenia, however less is known in people with first-episode psychosis (FEP). The aim of the study is to assess the effectiveness of MCT+ in FEP regarding symptoms and cognitive insight.

Methods

A random clinical trial was performed with people with FEP from 10 clinical centers of Spain. One group received ten sessions of MCT+ and the other group received TAU. A total of 75 patients were included in the study, however only 40 finished the final assessment. Patients were assessed before treatment, post-treatment and 6 month follow-up. The assessment includes a battery of instruments for the main aims the Positive and Negative Syndrome Scale (PANSS) and the Beck Cognitive Insight (BCIS) will be analyzed. Repeated measures statistical test were used in order to assess differences between groups.

Results

Both groups improved in Positive symptoms, in the MCT+ group the difference was 5.18 (SD=6.8) with a significance of p=0.002, while in the TAU group the difference was 3.38 (SD=4.9) with a significance of p=0.005. Regarding cognitive insight, in the MCT+ group patients improved in Self-reflectiveness, obtaining a score in baseline of 15.21 (SD=5.52) and 18 (SD=5.28) in post-treatment (p=0.017). The TAU group did not improve in any subscale of the BCIS.

Discussion

The MCT+ seems to improve more in positive symptoms than TAU, although both interventions diminished the presence of these symptoms. The MCT+ improved the self-reflectiveness, being one of the important areas for the understanding of the daily social functioning in relation to other. Further analysis should be explored.
S36. TREATING NEGATIVE SYMPTOMS OF SCHIZOPHRENIA WITH A MOTIVE-SPECIFIC INTERVENTION: A RANDOMIZED BRIEF INTERVENTION TRIAL
Authors: Horisberger Rahel , Kaiser Stefan , Hartmann Matthias
Published: May 2020

Background

Motivational deficits seem to be one of the main barriers in the recovery process among psychosis patients and have been shown to be very treatment resistant. Motives are conscious and unconscious affect-based needs that influence behavior toward specific incentives. Thus, they constitute the basis of motivated behavior or the lack thereof. In this study, we investigated how individual differences in social motives relate to the phenomenology of motivational negative symptoms in patients with schizophrenia.

Methods

Fifty-nine patients with a diagnosis of schizophrenia were included into the sample. Negative symptoms were measured with the Brief Negative Symptom Scale and social motives with the Questionnaire for the Zurich Model of Social Motivation. Between-group differences, Pearson correlations and regression analysis were calculated. We replicated and extended the results in a second sample of forty-five psychosis patients, using the same methods.

Results

A comparison of healthy controls and schizophrenia patients revealed significant differences in social motives. Within the patient group, relationships between the characteristics of the individual motives, in particular the achievement motive, and the severity of the motivational negative symptoms, i.e. of asociality, avolition and anhedonia, could be described. In contrast, social motives cannot be associated with diminished expression, the non-motivational dimension of negative symptoms.

The duration of the disease seems to be an additional influencing factor: When comparing the motivational dispositions of first episode patients with those of healthy people, no differences were found. However, a relationship between the duration of the disease and the characteristics of social motives can be described.

Discussion

Explicit social motives stand in a relationship with motivational negative symptoms. Since implicit and explicit motives may diverge, the aim of our future research is to additionally investigate the association with implicit motives.

The inclusion of psychological factors helps to extend and improve psychotherapeutic interventions for psychosis patients. Since negative symptoms do not respond well to pharmacotherapy, further efforts in this direction are needed to understand the underlying mechanisms of this disease and to develop effective psychotherapy tools in the future.
S46. IMPAIRED ERROR-PROCESSING IN PATIENTS WITH FIRST-EPISODE PSYCHOSIS: AN EVENT-RELATED POTENTIAL STUDY
Authors: Park Jihye , Kim Minah , Jeong Hwang Wu , Soo Kwon Jun
Published: May 2020

Background

Impaired error/conflict monitoring as reflected in the event-related potentials (ERPs) has consistently reported in patients with schizophrenia. However, whether this impairment exist from the early phase of psychosis such as first-episode psychosis (FEP) is not yet been clearly reported. To investigate the presence of error/conflict monitoring deficit in early psychosis, we examined the error-related negativity (ERN), error-related positivity (Pe), and correct-response negativity (CRN) during the Go/Nogo task in the patients with FEP.

Methods

25 patients with and 25 age, sex matched healthy controls (HCs) were participated in electroencephalographic recording during the Go/Nogo task. Trials with error response was analyzed to define ERN at Fz electrode site and Pe at Pz electrode site. Trials with correct response was used for CRN analysis at Fz electrode site. Independent samples t-test was used to compare the amplitudes of ERP components between FEP and HC groups. Pearson’s correlation analysis was performed to reveal the relationship of altered ERP component with symptomatic severity in patients with schizophrenia.

Results

FEP patients showed significantly smaller ERN amplitude at Fz electrode site compared to HCs (t=-3.294, p=0.002). However, there was no difference of CRN (t=0.017, p=0.986) and Pe (t=1.806, p=0.077) amplitudes between FEP and HC groups. There was no significant correlation of symptomatic severity and ERN amplitude at Fz electrode site in FEP patients.

Discussion

These findings suggest that impairments in error/conflict monitoring as reflected by ERN amplitude exist from the early course of psychotic disorder. Future study with larger sample size and subjects at earlier phase such as clinical high risk for psychosis would be needed to confirm the findings of current study.
S81. METAMEMORY IMPAIRMENT ACROSS THE PSYCHOSIS TRAJECTORY: ASSOCIATIONS WITH SYMPTOM SEVERITY
Authors: Seabury Rashina , Bearden Carrie E , Ventura Joseph , Subotnik Kenneth L , Nuechterlein Keith H , Cannon Tyrone
Published: May 2020

Background

Schizophrenia is a psychiatric disorder characterized by a deficit in reality testing, most often manifest in the form of delusions and hallucinations. Because differentiating real from imagined experiences is critically dependent on episodic and associative memory, deficits in mnemonic processes could be involved in the genesis of impaired reality testing. Prior work has shown that individuals with psychosis exhibit impairment in metamemory, or, awareness and knowledge of one’s own memory and memory processes, and that these impairments may be relevant to the emergence and/or maintenance of psychotic symptoms.

Methods

In the present study, we used a verbal associative memory paradigm incorporating subject confidence ratings to examine differences in metamemory processes in three separate samples: patients with chronic schizophrenia (CHR; n = 34), patients with recent-onset (first-episode) psychosis (n = 49), and individuals at clinical high risk for psychosis (n = 29) compared to control groups (n = 24, n = 26, and n = 22, respectively). We used an analysis of variance design to examine group differences in confidence gap and knowledge corruption between patients and controls. We further assessed the association of both of these metrics to symptom severity in each patient sample.

Results

We found that both chronic and first-episode patients displayed significantly decreased confidence gap compared to healthy controls, with patients being more confident in incorrect memory retrievals and less confident in correct memory retrievals as compared to healthy controls. Additionally, compared to healthy controls, chronic patients and first-episode patients showed significantly increased knowledge corruption (the proportion of confident incorrect memory retrievals compared to all confident retrievals). While there were no group differences in confidence gap and knowledge corruption between CHR subjects and healthy controls, decreased confidence gap was significantly correlated with positive symptom severity in CHR subjects, as well as in first-episode subjects.

Discussion

These findings suggest that underlying deficits in metamemory processes may possibly reflect mechanisms involved in the development and/or maintenance of disrupted reality testing in those with and at risk for psychosis.