bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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.
S131. NEIGHBOURHOOD-LEVEL SOCIAL CAPITAL, MARGINALIZATION, AND THE INCIDENCE OF PSYCHOTIC DISORDERS IN TORONTO, CANADA: A RETROSPECTIVE POPULATION-BASED COHORT STUDY
Authors: Rotenberg Martin , Tuck Andrew , Anderson Kelly , McKenzie Kwame
Published: May 2020

Background

Previous studies have shown mixed results regarding the relationship between social capital and the risk of developing a psychotic disorder, and this has yet to be studied in North America. This study aims to examine the relationship between neighbourhood-level social capital, marginalization, and the incidence of psychotic disorders in Toronto, Canada.

Methods

A retrospective cohort of people aged 14 to 40 years residing in Toronto, Canada in 1999 (followed to 2008) was constructed from population-based health administrative data. Incident cases of schizophrenia spectrum psychotic disorders were identified using a validated algorithm. Voter participation rates in a municipal election were used as a proxy neighbourhood-level indicator of social capital. Exposure to neighbourhood-level marginalization was obtained from the Ontario Marginalization Index. Poisson regression models adjusting for age and sex were used to calculate incidence rate ratios (IRR) for each social capital quintiles and marginalization quintile.

Results

In the study cohort (n = 640,000) over the 10-year follow-up period, we identified 4,841 incident cases of schizophrenia spectrum psychotic disorders. We observed elevated rates of psychotic disorders in areas with the highest levels (IRR = 1.13, 95% CI 1.00–1.27) and moderate levels (IRR = 1.23, 95% CI 1.12–1.36) of social capital, when compared to areas with the lowest levels of social capital, after adjusting for neighbourhood-level indicators of marginalization. The risk associated with social capital was not present when analyzed in only the females in the cohort. All neighbourhood marginalization indicators, other than ethnic concentration, were significantly associated with risk.

Discussion

The risk of developing a psychotic disorder in Toronto, Canada is associated with socioenvironmental exposures. Social capital is associated with risk, however, the impact of social capital on risk differs by sex and social capital quintile. Across the entire cohort, exposure to all neighbourhood-level marginalization indicators, except ethnic concentration, impacts risk. Future research should examine how known individual-level risk factors, including immigration, ethnicity, and family history of a mental disorder may interact with these findings.
S139. PROGRESSIVE DETERIORATION OF WHITE MATTER TRACTS IN SCHIZOPHRENIA: A DIFFUSION MRI STUDY ON A LARGE SINGLE COHORT USING NORMATIVE MODELS
Authors: Hwang Tzung-Jeng , Tung Yu-Hung , Chen Chang-Le , Yang Li-Ying , Hsu Yung-Chin , Hwu Hai-Gwo , Liu Chen-Chung , Chien Yi-Ling , Hsieh Ming-Hsien , Lin Yi-Tin , Liu Chih-Min , Isaac Tseng Wen-Yih
Published: May 2020

Background

Current diffusion MRI studies of schizophrenia are limited by methodology and sample size. With normative models and the largest single-site cohort, we aimed to delineate a comprehensive profile of tract alteration in unaffected siblings, first-episode schizophrenia (FES), and chronic schizophrenia.

Methods

A total of 277 patients with schizophrenia, 81 unaffected siblings, and 1023 healthy people underwent diffusion-weighted imaging on the same 3T scanner. Generalized fractional anisotropy (GFA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), were sampled along 45 major neural tracts. A normative model was built from the images of 1023 healthy people; Z scores represented the normalized deviation of the index value from that of the age- and sex-matched healthy population.

Results

Widespread involvement of neural tracts was found in patients with FES, and the tracts connecting the prefrontal lobe were the most severely affected. In patients with chronic schizophrenia, virtually all neural tracts were altered, with the tracts connecting the sensorimotor cortex the least affected. A significant negative correlation was observed between GFA alterations and the duration of illness. In unaffected siblings, scattered tracts were involved in GFA, but not in MD or RD.

Discussion

The study revealed widespread white matter involvement in the early stages of schizophrenia. The alteration continues to progress from the neural tracts connecting the prefrontal lobe to the entire brain. Compared to a large sample of normal controls, the attenuated peak and rapid decline of white matter GFA across the lifespan suggest that schizophrenia is associated with neurodevelopmental and neurodegenerative abnormalities of white matter.
S145. CORTICO-THALAMIC DYSCONNECTIVITY LINKS WITH ABERRANT STRIATAL DOPAMINE IN SCHIZOPHRENIA A SIMULTANEOUS 18F-DOPA-PET/RESTING-STATE FMRI STUDY
Authors: Avram Mihai , Brandl Felix , Knolle Franziska , Cabello Jorge , Leucht Claudia , Scherr Martin , Mustafa Mona , Koutsouleris Nikolaos , Leucht Stefan , Ziegler Sibylle , Sorg Christian
Published: May 2020

Background

In schizophrenia, among the most consistent brain changes are both aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei; however, it is unknown whether these changes are pathophysiologically related. Such a relationship is expected because cortico-thalamic-connectivity is modulated by striatal dopamine within topographically distinct, parallel but interacting cortico-basal-ganglia-thalamic circuits. We hypothesized: (1) Within-circuits, aberrant striatal dopamine contributes to aberrant cortico-thalamic-iFC, specifically, associative-striatum dopamine contributes to salience-network-thalamic-iFC, and sensorimotor-striatum dopamine to auditory-sensorimotor-network-thalamic-iFC. (2) Due to between-circuits interactions following an anterior-to-posterior gradient, salience-network-centered-system changes contribute to auditory-sensorimotor-network-centered-system changes.

Methods

To test these hypotheses, 19 patients with schizophrenia during symptomatic remission of positive symptoms and 19 age- and sex-comparable controls underwent simultaneous fluorodihydroxyphenyl-L-alanine positron emission tomography (18F-DOPA-PET) and resting-state functional magnetic resonance imaging (rs-fMRI). The influx constant kicer based on 18F-DOPA-PET was used to measure dopamine synthesis capacity (DSC), indicating striatal dopamine function; correlation coefficients between rs-fMRI time-series of cortical networks and thalamic regions-of-interest were used to measure iFC.

Results

In the salience-network(SAL)-centered-system, patients had reduced associative-striatum-DSC, which correlated positively with SAL-mediodorsal-thalamus-iFC and mediated the reduction of SAL-thalamic-iFC in patients. In the auditory-sensorimotor-network(ASM)-centered-system, patients had reduced sensorimotor-striatum-DSC, which correlated positively with ASM-ventrolateral-thalamus-iFC, but did not mediate increased ASM-thalamic-iFC in patients. Finally, aberrant DSC and iFC of the SAL-centered-system mediated corresponding changes in the ASM-centered-system.

Discussion

Results demonstrate that cortico-thalamic-dysconnectivity links with aberrant striatal dopamine in schizophrenia - in a topographically distinct way, with an anterior-to-posterior gradient, and primary changes in the SAL-centered system.
S150. EMOTIONAL BEHAVIOUR IN HIGH-RISK AND FIRST-EPISODE PSYCHOSIS
Authors: Falkenberg Irina , Tseng Huai-Hsuan , Modinos Gemma , Wild Barbara , McGuire Philip , Allen Paul
Published: May 2020

Background

Studies indicate that people with schizophrenia and first-episode psychosis experience deficits in their ability to accurately detect and display emotions through facial expressions, and that functioning and symptoms are associated with these deficits. This study aims to examine how emotion recognition and facial emotion expression are related to functioning and symptoms in a sample of individuals at ultra-high risk, first-episode psychosis and healthy controls.

Methods

During fMRI, we combined the presentation of emotional faces with the instruction to react with facial movements predetermined and assigned. 18 patients with first-episode psychosis (FEP), 18 individuals at ultra high risk of psychosis (UHR) and 22 healthy controls (HCs) were examined while viewing happy, sad, or neutral faces and were instructed to simultaneously move the corners of their mouths either (a). upwards or (b). downwards, or (c). to refrain from movement. The subjects’ facial movements were recorded with an MR-compatible video camera.

Results

Neurofunctional and behavioral response to emotional faces were measured. Analyses have only recently commenced and are ongoing. Full results of the clinical and functional impact of behavioral and neuroimaging results will be presented at the meeting.

Discussion

Increased knowledge about abnormalities in emotion recognition and behaviour as well as their neural correlates and their impact on clinical measures and functional outcome can inform the development of novel treatment approaches to improve social skills early in the course of schizophrenia and psychotic disorders.
S152. DIAGNOSTIC CLASSIFICATION OF SCHIZOPHRENIA USING 3D CONVOLUTIONAL NEURAL NETWORK WITH RESTING-STATE FUNCTIONAL MRI
Authors: Kim Harin , Woo Joo Sung , Ho Joo Yeon , Lee Jungsun
Published: May 2020

Background

Several machine-learning (ML) algorithms have been deployed in the diagnostic classification of schizophrenia. Compared to other ML methods, the 3D convolutional neural network (CNN) has an advantage of learning complex and subtle patterns in data and preserving spatial information, which is a more suitable tool for brain imaging data. Although resting-state functional MRI (rsfMRI) data has been used in previous ML studies relating to the diagnostic classification of schizophrenia, a limited number of studies have been conducted using resting-state functional connectivity resulted from group independent component analysis (ICA) and dual regression. The objective of this study was to investigate whether a successful diagnostic classification of schizophrenia vs. healthy controls could be achieved by the 3D CNN using resting-state networks in which areas with a significant group difference in activity existed.

Methods

T1 and rsfMRI data were collected in 46 patients with recent-onset schizophrenia and 22 healthy controls. In the pre-processing steps of rsfMRI, the ICA-based automatic removal of motion artifacts was applied to subject-level ICA results and the resulting rsfMRI data were temporally concatenated for group ICA and dual regression. The executive control and auditory networks had areas with significantly higher activity in the control group compared with the patient group. The independent components (ICs) respective to the executive control and auditory networks were used as input for the 3D CNN model which was developed to discriminate the schizophrenia patients from the healthy controls.

Results

The 3D CNN model using the executive control and auditory networks as inputs showed classification accuracies of 65~70%, and error rates of 30~35% approximately.

Discussion

Our findings suggest that the 3D CNN model using rsfMRI data can be useful for learning patterns implicated in schizophrenia and identifying discriminative patterns of schizophrenia in brain imaging data.
S154. TOBACCO SMOKING AND CLINICAL HIGH RISK: A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE EVIDENCE
Authors: De Micheli Andrea , van Lawick van Pabst Albertine , Yossef Enass , McGuire Philip , Fusar-Poli Paolo
Published: May 2020

Background

There is converging evidence that youths at clinical high risk (CHR) are not only likely to develop the first episode of psychosis but also to develop poor physical outcomes. Some physical health risk factors - such as smoking - have been shown to increase the probability of a frank onset of psychosis in those at risk. A meta-analysis conducted in psychotic patients confirmed that daily tobacco use is associated with an increased risk of psychosis. A significant association between any attenuated psychotic symptoms (that characterize CHR state) and cigarette smoking has been recently shown in a study conducted in South London.

Nowadays, it is not completely clear how these findings would translate to the CHR population but a better understanding of how physical health parameters could affect psychopathological outcomes could be beneficial for these vulnerable clinical populations. To shed light on the percentage of smokers in CHR populations, an updated systematic review and meta-analysis of the literature has been carried out. Our main aim was to test whether the probability of being a smoker was higher in the CHR subjects or in the control group.

Methods

The literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We systematically scrutinized from literature inception to 2019 the following on-line databases: Web of Science Core Collection, BIOSIS Citation Index, KCL-Korean Journal Database, MEDLINE, Russian Science Citation Index, SCiELO Citation Index.

We have considered all the relevant studies reporting the smoking status in CHR subjects and in control groups.

We used the odds ratio (OR) as effect size measure and data were pooled using a random effect approach.

Results

Preliminary data show that CHR individuals were more likely to use tobacco that matched healthy controls. Specifically, the overall OR of 2.016 (p<.001 95%CI=1.476–2.749) indicated a higher likelihood that CHR individuals would use tobacco compared to controls. Heterogeneity was not significant (I²=30.193 p=0.11). The visual inspection of funnel plots did not reveal a clear suggestion for publication bias and the Egger’s test was non-significant (p=0.10).

Discussion

Our systematic review and meta-analysis suggest that is crucial to investigate physical health outcomes such as tobacco use as part of clinical practice in CHR services. Unfortunately, current CHR assessment tools are entirely based on the measurement of psychopathological features and do not include an assessment of these parameters on a regular basis.
S156. PUBLIC ATTENTION TO CRIME OF SCHIZOPHRENIA AND ITS CORRELATION WITH USE OF MENTAL HEALTH SERVICES IN PATIENTS WITH SCHIZOPHRENIA
Authors: Park Hyunwoo , Lee Yu Sang , Yup Lee Sang , Lee Seungyeoun , Sue Hong Kyung , Koike Shinsuke , Soo Kwon Jun
Published: May 2020

Background

This study was performed to examine the effects of the public attention to ‘crime of schizophrenia’ on the use of mental health services in patients with schizophrenia using big data analysis in Korea.

Methods

Data on the frequency of internet searches for ‘crime of schizophrenia’ and the patterns of mental health service utilization by patients with schizophrenia spectrum disorders by month were collected from Naver big data and the Health Insurance Review and Assessment Services in Korea, respectively. Their correlations in the same and following month for lagged effect were examined.

Results

The number of outpatients correlated negatively with public attention to ‘crime of schizophrenia’ in the same month. The lagged relationship between public attention and the number of admissions in psychiatric wards was also found. In terms of sex differences, the use of outpatient services among female patients correlated negatively with public attention in the same month while the number of male patients’ admissions in both same and following month correlated positively with public attention.

Discussion

These findings suggested that public attention to ‘crime of schizophrenia’ could negatively affect illness behavior in patients with schizophrenia.
S163. GLUTAMATERGIC METABOLITES IN THE PSYCHOSIS SPECTRUM: FROM HIGH RISK SAMPLES TO FIRST EPISODE PSYCHOSIS
Authors: Fortea Adriana , Masias Mireia , Pariente Jose , Ilzarbe Daniel , Badia Francina , Valli Isabel , De la Serna Elena , Baeza Inmaculada , Castro-Fornieles Josefina , Sugranyes Gisela
Published: May 2020

Background

The N-methyl-D-aspartate receptor hypofunction model of schizophrenia suggests that dysfunction of these receptors leads to an excess release of glutamate and could explain the brain structural abnormalities characterizing these patients. However, glutamatergic pathways underlying transition to psychosis are yet unclear.

Methods

Youth with recent onset psychosis (FEP), within the first 5 years of disease, individuals with high risk for psychosis (HR) –including participants with psychosis risk syndrome meeting SIPS/SOPS criteria and offspring of parents with bipolar disorder or schizophrenia –, and healthy volunteers, were recruited and scanned with a 3T Siemens scanner. Magnetic resonance spectroscopy was performed using a 2x2x2 cm3 voxel (VOI) placed in the middle frontal region. Ratios of glutamate (Glu), and glutamate + glutamine (Glx) were quantified using LCModel.

Results

18 adolescents with FEP, 33 HR and 32 healthy controls (HC) were included in the analysis. There were no significant differences between groups in mean age (16.4±2.1 vs 15.7±2.7 vs 16.8±1.9; F=2.0, p=.139), but there were trend-level differences in gender (%females: 33.3% vs 57.6% vs 68.8%; Х2=5.9, p=.052). Multivariate models controlling for gender showed a trend-level effect of group in Glu (F=2.9, p=.062), but not in Glx. Post-hoc pairwise contrasts for Glu revealed significantly higher Glu levels in HR individuals (1.38±0.16) compared to FEP (1.27±0.20) and HC (1.31±0.15).

Discussion

Our findings support that increased Glu in the prefrontal cortex may index risk of psychosis from the early stages of the disease, during adolescence. Our observations suggest a possible hyperglutamatergia in premorbid stages that may normalize –or even decrease – after illness onset, possibly related to treatment or compensatory mechanisms. While requiring replication in a larger sample and including follow-up through transition in HR individuals, our findings raise the possibility that abnormal glutamatergic metabolism in the prefrontal cortex could be used as a potential biomarker of illness and putative treatment target.
S165. GLUTAMATERGIC ABNORMALITIES IN EARLY SCHIZOPHRENIA AND BIPOLAR DISORDER MEASURED USING WHOLE-BRAIN SPECTROSCOPY
Authors: Lenroot Rhoshel , Upston Joel , Mayer Grace , Jones Thomas , Maudsley Andrew , Gasparovic Charles , Tohen Mauricio , Bustillo Juan
Published: May 2020

Background

Glutamatergic abnormalities in schizophrenia and bipolar disorder gave been identified using proton magnetic resonance spectroscopy (1H-MRS). Although schizophrenia and bipolar disorder are both known to involve extensive brain networks, most MRS studies have been done using single-voxel techniques. In this study we used whole brain 1H-MRS to examine glutamine-plus-glutamate (Glx) in early schizophrenia and bipolar disorder to examine metabolic abnormalities associated with affective and non-affective psychosis and with exposure to antipsychotic medication.

Methods

Three dimensional 1H-MRS was acquired in young schizophrenia (SCZ, N=36, 24 M, 22.8±3.9 years, 19 antipsychotic-naïve and 17 antipsychotic-treated), bipolar (N=13, 5 antipsychotic-naïve and 8 antipsychotic-treated), schizoaffective-bipolar type (N= 3, 2 antipsychotic-naïve and 1 antipsychotic-treated) subjects, and healthy controls (HC, N=29, 17M, 23±4.4yrs). Glx, N-acetylaspartate, choline, myo-inositol and creatine group contrasts from all individual voxels that met spectral quality were analyzed in common brain space (voxel-wise p-threshold=0.001), followed by cluster-corrected alpha value (p<0.05). Bipolar subjects (N=13) and schizoaffective-bipolar type (N=3) were combined (SBP) (N=16, 11M, 21.9±2.9yrs, 7 antipsychotic naïve and 9 antipsychotic-treated).

Results

SCZ subjects compared to HC had lower Glx in the left superior (STG) and middle temporal gyri (16 voxels, p=0.04) and increased creatine in two clusters involving left temporal, parietal and occipital regions (32, and 18 voxels, p=0.02 and 0.04, respectively). Antipsychotic-treated and naïve SCZ had similar Glx reductions (8/16 vs 10/16 voxels respectively, but p’s>0.05). However, creatine was higher in antipsychotic-treated vs HC’s in a larger left hemisphere cluster (100 voxels, p=0.01). Also in treated SCZ, choline was increased in left middle frontal gyrus (18 voxels, p=0.04). Finally, in antipsychotic-naive SCZ, NAA was reduced in right frontal gyri (19 voxels, p=0.05) and myo-inositol was reduced in the left cerebellum (34 voxels, p=0.02). SBP subjects had no significant differences from HC in any area of the brain for any of the metabolites at a voxel-wise p-threshold of 0.001. A cluster of reduced Glx was found at in the right cuneus and precuneus (276 voxels, p=0.05) using a less stringent voxel-wise p-threshold of p< 0.05.

Discussion

Data-driven spectroscopic brain examination supports the presence of reductions in Glx in the left STG early in the course of schizophrenia; this was not seen in individuals with bipolar symptoms. A trend toward decreased Glx in the right cuneus and pre-cuneus in bipolar and schizoaffective patients is consistent with previous findings of abnormal function in this area. The left STG may be a critical target for postmortem and neuromodulation studies in schizophrenia studies.
S166. EFFECTIVE CONNECTIVITY OF FRONTOSTRIATAL SYSTEMS IN FIRST-EPISODE PSYCHOSIS
Authors: Sabaroedin Kristina , Razi Adeel , Aquino Kevin , Chopra Sidhant , Finlay Amy , Nelson Barnaby , Allott Kelly , Alvarez-Jimenez Mario , Graham Jessica , Baldwin Lara , Tahtalian Steven , Yuen Hok P , Harrigan Susy , Cropley Vanessa , Pantelis Christos , Wood Stephen , O’Donoghue Brian , Francey Shona , McGorry Patrick , Fornito Alex
Published: May 2020

Background

Neuroimaging studies have found dysconnectivity of frontostriatal circuits across a broad spectrum of psychotic symptoms. However, it is unknown whether dysconnectivity within frontostriatal circuits originates from disrupted bottom-up or top-down control signaling within these systems. Here, we used dynamic causal modelling (DCM) to examine the effective connectivity of frontostriatal systems in first-episode psychosis (FEP).

Methods

A total of 55 FEP patients (26 males; mean [SD] age = 19.24 [2.89]) and 24 healthy controls (15 males; mean [SD] age = 21.83 [1.93]) underwent a resting-state functional magnetic resonance imaging protocol. Biologically plausible connections between eight left hemisphere regions encompassing the dorsal and ventral frontostriatal systems were modelled using spectral DCM. The regions comprise dorsolateral prefrontal cortex, ventromedial prefrontal cortex, anterior hippocampus, amygdala, dorsal caudate, nucleus accumbens, thalamus, and the midbrain. Effective connectivity between groups were assessed using a parametric Bayesian model. Associations between effective connectivity parameters and positive symptoms, measured by the Brief Psychiatric Rating Scale positive subscale, was assessed in the patient group in a separate Bayesian general linear model.

Results

DCM shows evidence for differences in effective connectivity between patients and healthy controls, namely in the bottom-down connections distributed in the frontostriatal system encompassing the hippocampus, amygdala, striatum, and midbrain. Compared to healthy controls, patients also demonstrated increased disinhibition of the midbrain. In patients, positive symptoms are associated with increased top-down connections to the midbrain. Outgoing connection from the midbrain to the nucleus accumbens is also increased in association with positive symptoms.

Discussion

Aberrant top-down connectivity in the frontostriatal system in patients is consistent with top-down dysregulation of dopamine function in FEP, as dopaminergic activity in the midbrain is proposed to be under the control of higher brain areas. In patients, increased self-inhibition of the midbrain, as well as symptom associations in both ingoing and outgoing connections of this region, are congruous with hyperactivity of the midbrain as proposed by the dopamine dysregulation hypothesis. Here, we demonstrate that mathematical models of brain imaging signals can be used to identify the key disruptions driving brain circuit dysfunction, identifying new targets for treatment.
S167. THE EFFECT OF THE CATECHOL-O-METHYLTRANSFERASE VAL153MET POLYMORPHISM ON TEMPORAL INTERHEMISPHERIC CONNECTIVITY AND LANGUAGE COMPREHENSION IN PATIENTS WITH SCHIZOPHRENIA
Authors: Eun Kim Sung , Soo Lee Kang , Hoon Kim Jeong , Bang Minji , Lee Sang-Hyuk
Published: May 2020

Background

Difficulties in language comprehension is the major psychopathology in schizophrenia. The catechol-O-methyltransferase (COMT) Val153Met polymorphism, a candidate gene related to the pathogenesis of schizophrenia, is associated with higher cognitive abilities including language comprehension. At the brain level, this function is known to be supported by reciprocal communication via transcallosal projections between the temporal regions. This study investigated the effect of the COMT Val153Met polymorphism on white matter (WM) integrity of the tapetum, which connects the bilateral temporal lobes, and language comprehension in patients with schizophrenia.

Methods

Ninety patients with schizophrenia participated in this study. The COMT Val153Met polymorphism was analyzed, and the genotype groups were divided into Val-allele homozygotes and Met-allele carriers (45 participants in each group). Diffusion tensor imaging (DTI) data were acquired from all participants. Fractional anisotropy (FA) values were extracted from the bilateral tapetum. The levels of language comprehension were measured using verbal comprehension subtests of the Korean version of WAIS.

Results

Val-allele homozygotes showed higher FAs in left tapetum than Met-allele carriers (mean ± SD: val-allele homozygotes = 0.809 ± 0.059, Met-allele carriers = 0.777 ± 0.079; t = 2.16, p = 0.034). The right tapetum FAs were not different between two groups. (mean ± SD: val-allele homozygotes = 0.772 ± 0.065, Met-allele carriers = 0.748 ± 0.061; t = 1.83, p = 0.071). Although the sum of verbal comprehension subtest scores did not differ between two groups, only Val-allele homozygotes showed a negative correlation between the sum scores and left tapetum FAs (val-allele homozygotes: r = -0.426, p = 0.021, Met-allele carriers: r = -0.193, p = 0.275).

Discussion

This study suggests that the COMT Val153Met polymorphism may be associated with structural changes in interhemispheric WM tracts connecting the temporal regions. Furthermore, COMT-associated WM changes may contribute to individual variations in language comprehension of patients with schizophrenia, particularly Val-allele homozygotes. We expect that our findings provide some clues for understanding the interaction between the brain and genes in patients with schizophrenia.
S172. GLUTAMATE RELATED CONNECTIVITY DISTURBANCES OF THE SALIENCE AND DEFAULT MODE NETWORKS IN PSYCHOSIS
Authors: McCutcheon Rob , Pillinger Toby , Jauhar Sameer , Pepper Fiona , Rogdaki Maria , Howes Oliver
Published: May 2020

Background

Cortical dysconnectivity and dysfunctional glutamatergic signalling are both implicated in the pathophysiology of psychotic illness. The relationship between these two systems, and the relevance to psychotic disorders remains unknown.

Methods

50 individuals with a psychotic disorder and 54 healthy controls received baseline imaging using 1H-MRS to measure anterior cingulate glutamate concentrations, and resting state MRI to characterise functional brain networks. These measures were subsequently repeated following 3 days treatment with either the glutamatergic regulator riluzole (N=36), or a dopamine antagonist (N=14). The network-based statistic was used to examine relationships between glutamate concentrations and connectivity of the salience and default mode networks in patients and controls, and to investigate how this changed following pharmacological manipulation.

Results

In healthy controls higher baseline anterior cingulate glutamate concentrations were associated with reduced salience network connectivity, particularly for interhemispheric connections. This pattern was not seen in patients, and the greater the divergence from the relationship observed in controls, the greater the severity of negative symptoms. Default mode-salience internetwork connectivity was greater in patients compared to controls, and inversely correlated with baseline glutamate concentrations. Furthermore, riluzole associated changes in glutamate concentrations were associated with an inverse change in internetwork connectivity suggesting a causal relationship.

Discussion

Individuals with a psychotic disorder showed marked alterations in the relationship between anterior cingulate cortex glutamate concentration and connectivity of the salience and default mode networks. A pharmacological challenge with a glutamate regulating agent modulated this association, highlighting that the relationship is potentially malleable.
S201. HIPPOCAMPAL SUBFIELD VOLUMES AND CHANGE IN BODY MASS OVER 12 MONTHS OF TREATMENT IN FIRST-EPISODE SCHIZOPHRENIA SPECTRUM DISORDERS
Authors: Du Plessis Stéfan , Luckhoff Hilmar , Kilian Sanja , Asmal Laila , Scheffler Frederika , Phahladira Lebogang , Olivier Riaan , Emsley Robin
Published: May 2020

Background

In this study, we explored the relationship between hippocampal subfield volumes and change in body mass over 12 months of treatment in 90 first-episode schizophrenia spectrum disorder patients (66 males, 24 females; mean age= 24.7±6.8 years).

Methods

Body mass index was assessed in patients at baseline, and at months 3, 6, 9 and 12. Hippocampal subfields of interest were assessed using a segmentation algorithm included in the FreeSurfer 6.0 software program.

Results

Linear regression analysis showed a significant interactive effect between sex and anterior hippocampus size as a predictor of change in body mass over 12 months, adjusting for age, substance use, treatment duration, and posterior hippocampal volumes. In an exploratory sub-analysis, partial correlations revealed a significant association between weight gain and smaller CA1, CA3 and subiculum volumes in females, but not males, adjusting for age and substance use, with similar trends evident for the CA4 and presubiculum subfields.

Discussion

In conclusion, our findings suggest that smaller anterior hippocampal subfields are associated with the development of weight gain over the course of treatment in first-episode schizophrenia spectrum disorders in a sex-specific fashion, and may partly explain the more severe and ongoing increase in body mass evident for female patients.
Combined vascularized bone graft and scaphocapitate fusion in the treatment of stage III(b) Kienböck’s disease: a cohort study involving 11 patients
Authors: Safoury Yasser , Atteya Amr
Published: May 2020

Background:

The purpose of this study was to evaluate the results of combined scaphocapitate fusion and revascularization of the lunate for patients with stage III(b) Kienböck’s disease.

Methods:

Eleven patients with stage III(b) (Lichtman classification) Kienböck’s disease were identified. The inclusion criteria were stage III(b) Kienböck’s disease according to the Lichtman classification, with no previous surgical interventions, no radiocarpal arthritis, and intact lunate articular surfaces proven by plain radiographs, MRI, and intraoperative wrist arthroscopy. All patients were scheduled for scaphocapitate fusion and lunate revascularization. Intraoperative wrist arthroscopy was mandatory for the plan of treatment.

Results:

In all patients there was radiographic evidence of union and bone consolidation at the carpal fusion site at a mean of 8 wk. MRI was obtained 1 yr after the procedure and showed revascularization of the lunate in all patients. Postoperative serial radiographs showed improvement and maintenance of the lunate height and diameter. Postoperatively, wrist extension range of motion showed a mean improvement of 11.3%, while wrist flexion range of motion showed a mean improvement of 24.32%. Mean improvement in grip strength was 106.33%. VIsual analog scale (VAS) for pain showed a mean improvement of 71.02%. Disability of the Arm, Shoulder, and Hand (DASH) score showed a mean improvement by 77.67%.

Conclusions:

Revascularization and restoration of lunate anatomy together with an unloading procedure gives better results in the treatment of stage III(b) Kienböck’s disease. This technique prevents further collapse of the lunate with satisfactory long term results. Intraoperative wrist arthroscopy is mandatory to prove the intact lunate articular surface.

Level of Evidence:

Level IV.
Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Patients With Coronavirus Disease 2019
Authors: Shyh Grace I. , Nawarskas James J. , Cheng-Lai Angela
Published: May 2020

When the coronavirus disease 2019 (COVID-19) wreaked an unprecedented havoc of an escalating number of deaths and hospitalization in the United States, clinicians were faced with a myriad of unanswered questions, one of the them being the implication of the renin–angiotensin–aldosterone system in patients with COVID-19. Animal data and human studies have shown that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) increase the expression of ACE2. ACE2 is an enzyme found in the heart, kidney, gastrointestinal tract, and lung and is a coreceptor for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV2), the virus responsible for COVID-19. Therefore, one can speculate that discontinuing ACE inhibitor or ARB therapy may lead to decreased ACE2 expression, thereby attenuating the infectivity of SARS-CoV-2, and mitigating the disease progression of COVID-19. However, several studies have also shown that ACE2 exhibits reno- and cardioprotection and preserves lung function in acute respiratory distress syndrome, which would favor ACE inhibitor or ARB therapy. This article is to examine and summarize the 2 opposing viewpoints and provide guideline recommendations to support the use or discontinuation of ACE inhibitors and ARBs in patients with COVID-19.
Perils of Antithrombotic Transitions: Effect of Oral Factor Xa Inhibitors on the Heparin Antifactor Xa Assay
Authors: Ahuja Tania , Yang Irene , Huynh Quy , Papadopoulos John , Green David
Published: May 2020

Background:

Oral factor Xa inhibitors (OFXais) may interfere with the heparin antifactor Xa (antiXa) assay. The best method to measure heparin activity during the transition from an OFXai to intravenous (IV) unfractionated heparin (UFH) remains unknown. This study aimed to assess the safety and effectiveness of transitioning from an OFXai to UFH.

Methods:

A retrospective analysis was conducted of patients with supratherapeutic antiXa levels on UFH who received either apixaban or rivaroxaban within 72 hours before UFH initiation at NYU Langone Health. The primary objective was to identify the incidence of interference on the heparin antiXa assay due to OFXai exposure in the previous 72 hours. The secondary outcomes included the indication for transition to UFH and the rate of thromboembolic and bleeding events.

Results:

A total of 93 patients with supratherapeutic antiXa activity levels with prior OFXai use were reviewed. Moderate renal impairment, defined as creatinine clearance less than 49 mL/min, was present in 67 (72%) patients. The primary indication for transition from OFXai to UFH was in anticipation for a procedure, and it occurred in 37 (40%) patients. There were 3 major bleeding events and 3 clinically relevant nonmajor bleeding events. No thromboembolic events occurred.

Conclusions:

This study assessed the prevalence of supratherapeutic antiXa levels and clinical outcomes during the transition from OFXais to UFH. Health care systems should develop guidelines to assist clinicians in monitoring antiXa activity in patients undergoing a transition from an OFXai to UFH. It is also important to assess the patient's underlying thromboembolic and bleeding risks.
Short-term Safety of a Silicone Gel–filled Breast Implant: A Manufacturer-sponsored, Retrospective Study
Authors: Yoon Seanhyuck , Chang Jae-Hoon
Published: May 2020

Background:

Currently, 8 different brands of a silicone gel–filled breast implant are commercially available in Korea. But the superiority of short-term safety has not been established.

Methods:

A total of 709 patients (1,418 breasts) received an implant-based augmentation mammaplasty. We compared a 1-year incidence of complications and complication-free survival among the breast implants. Moreover, we performed a subgroup analysis of the patient cohorts by excluding cases associated with a periareolar incision, revision or reoperation, and anatomic implants.

Results:

In our series, 1-year incidences of complications were 0.55% (1/182), 3.14% (5/159), 5.19% (7/135), and 6.58% (10/152) in patients receiving the BellaGel/BellaGel SmoothFine, the Mentor CPG, the Matrix, and the Motiva Ergonomix, respectively. Moreover, the incidence of capsular contracture was 0.55%, 0.63%, 1.32%, and 3.70% in patients receiving the BellaGel/BellaGel SmoothFine, the Mentor CPG, the Motiva Ergonomix, and the Matrix, respectively. Furthermore, a complication-free survival was 24.82 ± 0.18, 22.23 ± 1.09, 22.15 ± 0.77, and 22.12 ± 1.07 months in patients receiving the BellaGel/BellaGel SmoothFine, the Motiva Ergonomix, the Mentor CPG, and the Matrix, respectively, except for the 2 other remaining products used for a smaller number of patients. However, a subgroup analysis showed no significant differences in a 1-year incidence of complication and complication-free survival among the BellaGel SmoothFine, the Motiva Ergonomix, and the Naturgel.

Conclusion:

It is impossible to draw a definite conclusion about the superiority of the short-term safety among the silicone gel–filled breast implants that are commercially available in Korea.