bluuebunny/crossref_metadata_2025_split huggingface dataset:
M142. INCREASED VENTRAL STRIATAL FUNCTIONAL CONNECTIVITY IN PATIENTS WITH SCHIZOPHRENIA DURING REWARD ANTICIPATION
Authors: Carruzzo Fabien , Kirschner Matthias , Kaiser Stefan 
Published: May 2020

Abstract

Background
Recent studies have pointed at the ventral striatum as one of the main candidates underlying motivational dysfunctions in schizophrenia. Patients with negative symptoms show decreased BOLD activity in the ventral striatum and this activity strongly correlates with apathy scores during reward anticipation.
While in patients with schizophrenia blunted ventral striatal activation during reward anticipation has been widely reported, little is known about abnormal striatal functional connectivity during reward anticipation. In this study, we performed generalized whole-brain psychophysiological interaction (gPPI) analyses using the right and left ventral striatum as seeds in schizophrenia patients with apathy and reduced ventral striatal activation from two published fMRI studies (Kirschner et al., 2016; Stepien et al., 2018).

Methods
Forty-four healthy controls (18 females, mean age = 31.1) and 40 patients with schizophrenia (10 females, mean age = 32.5) performed a variant of the Monetary Incentive Delay task within an fMRI design. Negative symptoms were assessed with the Brief Negative Symptoms Scale (BNSS). GPPI analyses were done using the PPPI toolbox on SPM 8. To examine potential difference in striatal functional connectivity, we performed two sample t-tests between patients with schizophrenia and healthy controls using the contrast [High Reward Anticipation – No Reward Anticipation].

Results
Patients with schizophrenia showed increased functional connectivity between the right ventral striatum and the anterior cingulate cortex, posterior cingulate cortex, cerebellum, motor cortex, parietal cortex, temporo-parietal junction and thalamus compared to controls (cluster-level FDR p&lt;0.05). No higher connectivity was found in controls compared to patients.
For the regions with increased functional connectivity, we performed correlations between the patients’ gPPI signal and apathy. We found significant correlations between apathy and functional connectivity between the right ventral striatum and the right posterior cingulate cortex (r=0.40, p&lt;.05) and right parietal cortex (r=0.39, p&lt;.05).

Discussion
Our preliminary results indicate that physiological changes in the ventral striatum lead to dysfunctional connectivity with a cortex-wide network, affecting both cortico-striatal-thalamic-cortical and cortico-striatal-thalamic-cerebellar pathways. In addition, we show that some of these changes are related to apathy levels. This work provides novel insights in cortico-striatal network dysfunction during reward processing in patients with schizophrenia.
M151. DIFFERENCES IN PATTERN OF OBESITY BETWEEN PEOPLE WITH SCHIZOPHRENIA LIVING IN CHINA AND IN AUSTRALIA
Authors: Galletly Cherrie , Wu Xiaoli , Han Zili , Liu Dennis 
Published: May 2020

Abstract

Background
People with psychotic disorders, including schizophrenia, suffer premature cardiovascular morbidity and mortality. Obesity is a major factor in cardiometabolic disorders in this population. There has been very little research investigating differences in patterns of obesity in diverse ethnic populations. Guidelines for treatment of complex comorbidities in people with schizophrenia and related psychoses may need to provide specific recomendations for different ethnic groups.

Methods
The Chinese sample consisted 192 subjects were recruited from the outpatients and inpatients department of the psychiatry department of the third affiliated hospital of Sun Yat-sen. All enrolled subjects were Chinese Han ethnicity, aged 16–45 years, with a diagnosis of schizophrenia according to ICD-10 criteria for schizophrenia, excluding other acute psychiatric disorders. The Australian sample (N=1825) were drawn from the Survey of High Impact Psychosis.
BMI and central obesity were measured in all subjects.

Results
10.3% of men and 4.7% of women in the China sample were obese (BMI&gt;30). In the Australian sample, 41.6% of men and 50.3% of women were obese. Overall, 7.8% of Chinese sample and 45.1% of the Australian sample were obese.
However, amongst the non-obese China sample, 41.7% of men and 53.1% of women had central obesity; the mean for all non-obese Chinese people was 46.7%. 73% of non-obese Australian men and 81.5% of non-obese Australian women had central obesity; the mean for all non-obese Australians was 76%.

Discussion
Chinese Han people with schizophrenia have much lower rates of obesity than the Australian sample. In both groups, rates of abdominal obesity were higher than rates of obesity as defined by BMI. These ethnic differences may help in understanding the high rates of cardiometabolic disorder in people with psychotic disorders in Western countries. They may also inform interventions to assist Western people with psychoses to maintain better physical health.
M168. CLINICAL-ANATOMICAL PHENOTYPES OF SCHIZOPHRENIA
Authors: Kirschner Matthias , Shafiei Golia , Markello Ross D , Markowsky Carolina , Talpalaru Alexandra , Hodzic-Santor Benazir , Devenyi Gabriel A , Lepage Martin , Chakravarty M Mallar , Dagher Alain , Misic Bratislav 
Published: May 2020

Abstract

Background
Although widespread structural brain abnormalities have been consistently reported in schizophrenia, their relation to the heterogeneous clinical manifestations is not well understood. Multivariate methods are needed to uncover covariance patterns between multiple symptom dimensions and system-wide brain imaging data.

Methods
This cross-sectional study used structural magnetic resonance imaging and neuropsychological data from 133 patients with chronic schizophrenia (48 female, 34.8±13.2 years) from the Northwestern University Schizophrenia Data and Software Tool (NUSDAST). We estimate disease-related voxel-wise tissue volume loss using deformation-based morphometry (DBM) of T1 weighted images. In patients with schizophrenia, multiple clinical dimensions including positive/negative symptoms and cognitive deficits, demographic data as well as individual tissue volume loss (DBM) were included in the multivariate model. Clinical-anatomical phenotypes were identified using partial least squares analysis.

Results
Multivariate analysis revealed three distinct clinical-anatomical phenotypes accounting for 27.5%, 15%, and 13% of the shared covariance between clinical-behavioural data and tissue volume loss (total of 55.5%). The first clinical-anatomical phenotype encompassed cognitive impairments, severity of negative symptoms and tissue volume loss within the default mode network and visual network. The second clinical-anatomical phenotype was associated with additional cognitive impairments and tissue volume loss within the frontoparietal and ventral attention network, while the third clinical-anatomical phenotype encompassed a mixed positive and negative symptoms phenotype and tissue volume loss within the dorsal attention network. Critically, the pattern of volume loss within the first most prevalent clinical-anatomical phenotype mediated (a*b) the effect of socioeconomic status on clinical outcome (cognitive performance and negative symptoms) (a*b=-0.033(0.008); P&lt;1.0×〖10〗^(-4); 95% CI [-0.049, -0.018]). Finally, we partly replicated the first clinical-anatomical phenotype in an independent sample of patients with schizophrenia (n=108).

Discussion
The heterogeneous clinical manifestation of schizophrenia can be significantly explained by three clinical-anatomical phenotypes. Despite their distributed topography, each phenotype is centered on a specific, well-defined set of intrinsic networks.
M176. INTESTINAL PERMEABILITY AND LOW-GRADE CHRONIC INFLAMMATION IN SCHIZOPHRENIA: DO THEY INFLUENCE COGNITION AND COGNITIVE RESERVE?
Authors: Anmella Gerard , Amoretti Silvia , Alfonso Miqueu , Cuñat Oriol , Safont Gemma , Pérez Ferran , Garcia-Portilla ,M Paz , De la Fuente Laura , Bernardo Arroyo Miguel , Arranz Belen 
Published: May 2020

Abstract

Background
Higher intestinal-permeability is known to cause low-grade chronic inflammation, which seems to participate in the development and worsening of psychotic disorders both in first-episode psychosis (FEP) and schizophrenia (SCZ) patients. Moreover, in psychotic disorders, inflammation has been linked to cognition and cognitive reserve (CR).
The aim of this study is to assess the relation between intestinal-permeability, low-grade chronic inflammation, cognition and cognitive reserve in psychotic disorders.

Methods
Observational, cross-sectional and multisite study including four centers in Spain (Grant from Fondo de Investigación Sanitaria, PI17/00246). A total of 500 adult patients with DSM-5 SCZ-spectrum disorder at any stage of the disease were recruited.
Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Disease severity was assessed using the Clinical Global Impression (CGI) scale and functioning was assessed using the Global Assessment of Functioning (GAF) scale. The intestinal-permeability was estimated with the “Permeable-Intestine-syndrome questionnaire”. The diet was assessed with the “Mediterranean-diet-adherence questionnaire”. Exercise was measured with the “International Physical Activity Questionnaire (IPAQ)”. Cognition was measured with the SCIP-S scale. CR was assessed with the Cognitive Reserve Assessment Scale in Health (CRASH), which is a scale developed to measure CR specifically for patients with severe mental illness.
Correlations between CRASH scores and the remainder variables were performed.

Results
For the present study we included only the subjects who had CRASH score, a total of 112 patients, 42.7% female, aged 40.61±12.4 (mean±SD). Substance use was present in 44.3%.
The CRASH score was 33.30±15.72 (mean±SD) and was associated with negative (but not positive) psychotic symptoms assessed by PANSS (PANSS negative; rp=-3.98; p=0.001, PANSS general; rp=-2.13; p=0.038, GAF; rp=0.410; p&lt;0.0001, CGI; rp=-0.30; p=0.002, IPAQ; rs=0.224; p=0.025 and the permeability-scale; rs=-0.266; p=0.008.
All cognitive domains (assessed by SCIP-S) were associated to CRASH: verbal learning immediate (rp=0.584; p&lt;0.0001) and differed (rp=0.515; p&lt;0.0001), working memory (rp=0.539; p&lt;0.0001), verbal fluency (rs=0.485; p&lt;0.0001) and processing speed (rp=0.584; p&lt;0.0001).
No significant associations were found with Mediterranean-diet scale (rs=0.195; p=0.056), IMC (rs=-0.192; p=0.063), C-reactive protein (rs=-0.104; p=0.278) and the IPAQ-resting scale and permeability-scale (rs=0.119; p=0.244).

Discussion
M193. CHANGES IN THEORY OF MIND DETECTED IN SCHIZOPHRENIA SPECTRUM DISORDERS- A LITERATURE REVIEW
Authors: Vasiliu Octavian 
Published: May 2020

Abstract

Background
Theory of mind (ToM) is a core feature of the social functioning because it influences the way an individual perceive other people’s mental states, and because responses to social cues are shaped by one’s ToM. Patients diagnosed with schizophrenia spectrum disorders (SSD) often present cognitive symptoms as part of their clinical manifestations, and there is a controversy about the relation of ToM deficiencies and more general cognitive features of schizophrenia and related disorders [1]. In order to find data that may clarify if ToM deficiencies are part of the schizophrenia cognitive dimension, or if they precede the onset of psychosis and simply coexist with other symptoms met in this type of disorders, a literature analysis was conducted.

Methods
This review included papers published between January 2000 and August 2019 in the main electronic databases (PubMed, Cochrane, EMBASE, CINAHL). Keywords used for database search were “schizophrenia spectrum disorders”, “schizophrenia”, “schizoaffective disorder”, “delusional disorder”, or “schizophreniform disorder” and “theory of mind”. There was included no age limit, and no exclusion criteria referred to the duration of the disorder.

Results
A number of 93 papers resulted after the primary search, but only 17 remained after de-duplication and application of inclusion/exclusion criteria. A study with young adults diagnosed with first episode of schizophrenia and matched controls (n=128) suggested that ToM deficits are partly independent of other cognitive functions [1]. Another study (n=1630 children 11–12 years old) reported specific alterations in ToM may be associated with specific types of psychotic experiences, and exaggerated type of ToM may index risk for developing psychosis and paranoid delusions in particular [2]. Adolescents who were genetically at high risk for schizophrenia had social skills impairments but no ToM deficits in a study [3]. Also, there is evidence for ToM deficits in the healthy relatives of schizophrenics, patients with delusional disorder, and individual with high schizotypy scores [4]. The hyper-connectivity in SSD has been confirmed on functional magnetic resonance imaging and default connectivity is correlated to and predictive of theory of mind performance [5]. A significant number of papers (n=10) did not formulate any clear argument to support the independent versus secondary status of the ToM deficits in relation to the SSD cognitive dimension.

Discussion
ToM deficiencies are important elements that have been associated with the social skills and functioning in patients with SSD, although it is not clear if these elements exist independently from other cognitive symptoms. Relatives of patients with SSD may present ToM deficits, and data exist about the correlation between ToM abnormalities and several positive symptoms of the SSD. However, more well designed trials are needed in order to confirm the association between ToM impairments and SSD.

References
M206. EFFECTS OF RISPERIDONE ON THE MRNA EXPRESSION OF PROTEINS INVOLVED IN INTRACELLULAR TRAFFICKING IN THE MICE EXPOSED TO SOCIAL DEFEAT STRESS
Authors: Zahra Rami Fatima , Ba Nguyen Thong , Min Lee Young , Oh Young-Eun , Chung Young-Chul 
Published: May 2020

Abstract

Background
Impaired intracellular trafficking has been proposed as a new key pathophysiology for neuropsychiatric disorders. The present study investigated the effects of risperidone on the mRNA levels of various proteins involved in intracellular trafficking, and dopaminergic receptors [long and short forms of the dopamine receptor D2 (DRD2) and dopamine receptor D1 (DRD1)] in several key brain regions of wild type adult mice exposed to social defeat stress.

Methods
C57BL/6J mice were subjected to chronic social defeat procedure for 10 consecutive days. The defeated mice were categorized into unsusceptible (UNS) and susceptible (SUS) groups based on performance in the social avoidance test. Animals were randomly divided into two groups, vehicle (VEH) and drug (DRUG) groups. Risperidone (RIS) was administered to the DRUG group at the dosage of 0.2 mg/kg, i.p. for 7days. After sacrifice and brain extraction, prefrontal cortex (PFC), hippocampus (HIP) and amygdala (AMY) were obtained. The mRNA levels of our target genes were measured by real time- PCR.

Results
In the VEH group, mRNA expression levels of GASP1 and ARF6 were decreased in the PFC and HIP, and AMY of UNS mice respectively compared to control mice. The mRNA expression of Rab4 was rather increased in the PFC of UNS mice compared to control mice. In the DRUG group, only mRNA expression level of GASP1 was decreased in the PFC of UNS mice compared to control mice.

Discussion
Our results indicate that social defeat stress induces changes in expression levels of GASP1, ARF6 and Rab4 in several key brain regions and these effects are blocked by risperidone. It may suggest that risperidone can prevent or treat an impairment of intracellular trafficking caused by defeat stress. As ARF6 is known to mediate recycling of D2 receptors and GASP-1 is involved in the lysosomal sorting of D2 receptor, our findings should be discussed with regard to the changes of mRNA expression levels of DRD2 and DRD1.
M210. GRIN2B METHYLATION IS RELATED TO PANSS EXCITED COMPONENT (PANSS-EC) IN SCHIZOPHRENIA
Authors: Fachim Helene , Fedorenko Olga Yu , Kornetova Elena G , Ivanova Svetlana A , Heald Adrian , Reynolds Gavin P 
Published: May 2020

Abstract

Background
Among the adversities found in schizophrenia, the dysfunctions in the glutamatergic system, specifically the N-methyl-D-aspartate receptor (NMDAR) are apparent. GRIN2B (coding a NMDAR subunit) has a critical role in synaptic plasticity and important participation in CNS neurodevelopment, this gene is closely associated with behavioural and cognitive impairments. One of the mechanisms that may underlie the deficiencies seen in the glutamatergic system in psychosis is DNA methylation as it is known to regulate gene expression. As part of a major study investigating the relationship of DNA methylation with schizophrenia and its symptom response to antipsychotic drug treatment, we determined whether methylation of the GRIN2B promoter region was associated with specific symptoms of schizophrenia determined by the Positive and Negative Syndrome Scale (PANSS).

Methods
Blood samples were collected from schizophrenia patients (n = 79) on admission to the study. Bisulphite conversion and pyrosequencing were used to determine methylation levels in 5 CpG sites in the GRIN2B promoter. PANSS score and the five factor subscores (Wallwork et al, 2012) at baseline and at 6 weeks was collected, and the change in PANSS following treatment was determined.

Results
Mean methylation at the five CpG sites was not associated with overall PANSS score or with the change in PANSS. However, a highly significant positive correlation of mean methylation with the baseline excited factor score (r=0.342, p=0.002), but with no other PANSS subscore, was found. No significant correlation with changes in PANSS, or in changes in subscores, over the treatment period was found.

Discussion
This is the first evidence showing GRIN2B methylation correlation with the excited component (EC) of schizophrenia symptoms. PANSS-EC is used to assess agitated patients (Lindenmayer et al., 2008, Montoya et al., 2011), and is valuable in identifying risks associated with agitation and aggression related to primary psychiatric disturbances. This result suggests that this GRIN2B epigenetic signature may relate to agitation and aggressive behaviour in schizophrenia.
S125. THE ROLE OF DUP, DUI AND POLYGENIC SCORE FOR SCHIZOPHRENIA ON COGNITION IN ATHENS FEP STUDY SAMPLE
Authors: Dimitrakopoulos Stefanos , Hatzimanolis Alex , Stefanatou Pentagiotissa , Xenaki Lida-Alkisti , Stefanis Nikos 
Published: May 2020

Abstract

Background
It remains unclear which biological mechanisms affect neurocognition in first episode psychosis (FEP) patients. There is minimal evidence from current literature suggesting an association between duration of untreated psychosis (DUP) or duration of untreated illness (DUI) and cognitive decline in FEP patients. It is still controversial whether genetic factors, such as polygenic risk score for schizophrenia, determine observed cognitive deficits. The study of interplay between DUP, DUI and genetic risk factors might be important to understand underlying pathways.

Methods
Ninety FEP patients where recruited during Athens First-Episode Psychosis Research study between 2015–2018. All participants provided inform consent. DUP for each patient was defined by NOS-DUP (Nottingham onset schedule: modified DUP version) assessment tool and DUI was determined using the symptom onset in schizophrenia (SOS) inventory. DNA was collected in order to create polygenic risk score (PGC) for schizophrenia for each individual using SNPs selected according to the significance of their association with the phenotype at nominal p-value thresholds of 0,05. WAIS-IV total score and subscales, i.e. Verbal Comprehension (VC), Perceptual Reasoning (PR), Working Memory (WM), Processing Speed (PS) and moreover index differences between these 4 subscales were applied as a measure of cognitive deficit.

Results
Generalized linear model analysis, after adjustment for years of education and gender, found no significant main effect of DUP, DUI or PGC on any cognitive subscale. Furthermore, conducting an exploratory analysis for possible interactions between DUP/DUI and PGC (n=90), we found statistically significant findings of DUP x PGC (F=8,175, p=,005) and DUI x PGC (F=5,592, p=,021) for the cognitive variable of VC/WM difference. The interplay between DUP and PCG and DUI and PGC was associated with observed differences between VM and WM in our FEP sample.

Discussion
Our preliminary results are consistent with recent literature suggesting that neurocognition is not determined by DUP, DUI or PGC for schizophrenia. Novel approach based on WAIS-IV indexes of interest allows to explore subtle differences between cognitive subdomains. Elucidating underlying interplay between genetic and disease-related mechanisms could be important to understand the core feature of cognitive deficit in FEP patients.
S126. THE RELATION OF THE PSYCHOSIS CONTINUUM WITH SCHIZOPHRENIA POLYGENIC RISK SCORE AND CANNABIS USE
Authors: Quattrone Diego , Ferraro Laura , Tripoli Giada , Rodriguez Victoria , Marino Paolo , Vassos Evangelos , Morgan Craig , Reininghaus Ulrich , Lewis Cathryn , Murray Robin , Di Forti Marta 
Published: May 2020

Abstract

Background
There has been much debate about whether research into psychosis should be conducted using symptom dimensions as opposed to diagnostic categories. Indeed, dimensions, like categories, may be practical but arbitrary tools for research and clinical practice; hence, they should not be based on psychometric data only. The aim of this study was to externally validate empirically derived symptom dimensions using combined genetic and environmental data. Specifically, we examined the hypothesis that the continuous multivariate distribution of psychosis is a function of cannabis use and genetic liability to schizophrenia, as summarised by polygenic risk score (SZ-PRS).

Methods
As part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study, we analysed a large multinational sample of First Episode Psychosis patients (FEP) and population controls, with available genotype and psychopathology information. Using item response modelling in Mplus, we estimated a bifactor model of psychotic symptoms in FEP, and of psychotic experiences in controls. Using PRSice, we built SZ-PRS by weighting individuals’ risk variants by the log(odds ratio), where the odds ratio was extracted from the latest summary statistics of Psychiatric Genomic Consortium mega-analyses on schizophrenia. Finally, we used linear regression to test the combined associations of the positive symptom/experience dimensions with SZ-PRS and daily/current cannabis use, separately in FEP and controls, after covarying for 10 ancestry principal components, sex, age, and primary diagnosis.

Results
The continuous distribution of psychosis was represented by two bi-factor models composed of 1) in FEP, one general psychosis factor and five specific dimensions; 2) in controls, one general psychosis factor and three specific dimensions.
Linear regression modelling showed that in 617 FEP, both daily cannabis use (B=0.31; 95%CI 0.11 to 0.52; p=0.002) and SZ-PRS (B=0.22; 95%CI 0.04 to 0.39; p=0.014) were independently associated with the dimension of positive symptoms. Similar results were found in 979 population controls, with a positive association of both current use of cannabis (B=0.26, 95%CI 0.06 to 0.46; p=0.011) and SZ-PRS (B=0.13, 95%CI 0.02 to 0.25; p=0.022) with the dimension of psychotic experiences.

Discussion
We found two factors associated with the latent dimensional structure of psychosis. SZ risk variants and cannabis use independently map onto specific dimensions of positive symptoms, contributing to variation across the psychosis continuum. Our study supports the theory that psychotic experiences in the general population are biologically similar to clinical psychotic symptoms.