T179. DO INDIVIDUALS IN A CLINICAL HIGH-RISK STATE FOR PSYCHOSIS DIFFER FROM HEALTHY CONTROLS IN THEIR CORTICAL FOLDING PATTERNS?

Background Volumetric brain differences between persons meeting criteria for a clinical high-risk state for psychosis (CHR) and healthy controls (HC) have been previously reported, yet little is known about potential abnormalities in surface-based morphological measures. Gyrification (i.e., the amount of cortical convolution) remains relatively stable across the lifespan and is minimally influenced by ubiquitous confounding factors (e.g., drug use, medication, or stress). Recently, a multi-site analysis conducted in 104 CHR persons found global increases in cortical gyrification compared to HC (Sasabayashi et al. 2017). If replicated, gyrification abnormalities in CHR could potentially serve as early neuromarkers of elevated risk, and thus could eventually be used to identify objectively and efficiently the CHR state. Methods A total of 124 CHR and 264 HC subjects were recruited as part of the PRONIA consortium (www.pronia.eu), a large-scale international longitudinal study currently consisting of 10 European sites. Cortical surfaces were reconstructed from structural MRI images using a volume-based, newly introduced technique called the Projection-Based-Thickness (PBT) as available in the SPM-based-toolbox CAT12. Local gyrification was quantified automatically across the whole brain as absolute mean curvature for each vertex of the brain surface mesh consisting of thousands of individual measurement points. Vertex-wise differences of curvature values were calculated applying a General Linear Model, corrected for age, gender and site effects. Results were investigated at corrected and uncorrected levels. Results We found no significant differences in vertex-wise gyrification between CHR and HC at either corrected or uncorrected levels (p>0.05). Further investigations of potential confounding site effects also did not reveal differences. Discussion Our preliminary findings suggest that CHR subjects do not show whole-brain gyrification abnormalities when compared with healthy subjects. These negative results agree with literature suggesting that cortical convolution might be more affected by neurodevelopmental or genetic factors, and thus deviations from normal patterns might not be detectable in heterogeneous samples of at-risk subjects wherein the etiology and ultimate prognosis is unknown. In order to better investigate differences in cortical folding and address the role of gyrification as neuroanatomical biomarker for psychosis, future investigations should focus on subgroups within CHR populations (e.g. patients groups defined by basic symptoms, ultra-high risk, or familial risk) in addition to specific analyses of individuals with higher neurodevelopmental (e.g., obstetric complications) or genetic (e.g., polygenic risk) loadings

Clearance of an epidemic clone of methicillin-resistant Staphylococcus aureus in a drug-use network: A follow-up study in Switzerland

Background: A single clone of methicillin-resistant Staphylococcus aureus (MRSA) was observed in a drug-use network starting in 1994, and was found to persist throughout 2001, with up to 19% MRSA colonization of intravenous drug users (IDUs). Recent clinical observations have shown low prevalences of this endemic drug clone among MRSA isolates. The goal of this study was to assess the evolution of MRSA carriage among IDUs. Methods: The survey took place from November 2008 to September 2009. Ten drug dispensary facilities took part. Demographic and clinical data including sex, history of MRSA, past hospitalization, use of antibiotics, and presence of wounds were collected. Screening of the nares, throat, and wounds was done. Results: Five hundred and fourteen swab specimens were obtained; 497 of them were nose/throat samples and 17 were wound swabs. MRSA was identified in 5 samples (1%). Four MRSA were found in nose/throat samples and 1 in a wound swab. Pulsed-field gel electrophoresis typing of the MRSA isolates revealed 2 different common endemic types: 4 were identified as the Zurich IDU clone and 1 as the Grison clone. Conclusions: The study shows a significant decline of MRSA colonization among IDUs. The underlying causes for this decline could not be determined fully, but we hypothesize a bundle of interventions as contributing: enhanced medical care, better wound management, isolation management, teaching IDUs basic hygiene techniques, and the national 'Four Pillars' policy. Hospital epidemiological policies such as pre-emptive isolation, length of isolation time, and screening procedures were adapted accordingly

Modeling Social Sensory Processing During Social Computerized Cognitive Training for Psychosis Spectrum: The Resting-State Approach

Background: Greater impairments in early sensory processing predict response to auditory computerized cognitive training (CCT) in patients with recent-onset psychosis (ROP). Little is known about neuroimaging predictors of response to social CCT, an experimental treatment that was recently shown to induce cognitive improvements in patients with psychosis. Here, we investigated whether ROP patients show interindividual differences in sensory processing change and whether different patterns of SPC are (1) related to the differential response to treatment, as indexed by gains in social cognitive neuropsychological tests and (2) associated with unique resting-state functional connectivity (rsFC). Methods: Twenty-six ROP patients completed 10 h of CCT over the period of 4–6 weeks. Subject-specific improvement in one CCT exercise targeting early sensory processing—a speeded facial Emotion Matching Task (EMT)—was studied as potential proxy for target engagement. Based on the median split of SPC from the EMT, two patient groups were created. Resting-state activity was collected at baseline, and bold time series were extracted from two major default mode network (DMN) hubs: left medial prefrontal cortex (mPFC) and left posterior cingulate cortex (PCC). Seed rsFC analysis was performed using standardized Pearson correlation matrices, generated between the average time course for each seed and each voxel in the brain. Results: Based on SPC, we distinguished improvers—i.e., participants who showed impaired performance at baseline and reached the EMT psychophysical threshold during CCT—from maintainers—i.e., those who showed intact EMT performance at baseline and sustained the EMT psychophysical threshold throughout CCT. Compared to maintainers, improvers showed an increase of rsFC at rest between PCC and left superior and medial frontal regions and the cerebellum. Compared to improvers, maintainers showed increased rsFC at baseline between PCC and superior temporal and insular regions bilaterally. Conclusions: In ROP patients with an increase of connectivity at rest in the default mode network, social CCT is still able to induce sensory processing changes that however do not translate into social cognitive gains. Future studies should investigate if impairments in short-term synaptic plasticity are responsible for this lack of response and can be remediated by pharmacological augmentation during CCT

The progression of disorder-specific brain pattern expression in schizophrenia over 9 years.

Age plays a crucial role in the performance of schizophrenia vs. controls (SZ-HC) neuroimaging-based machine learning (ML) models as the accuracy of identifying first-episode psychosis from controls is poor compared to chronic patients. Resolving whether this finding reflects longitudinal progression in a disorder-specific brain pattern or a systematic but non-disorder-specific deviation from a normal brain aging (BA) trajectory in schizophrenia would help the clinical translation of diagnostic ML models. We trained two ML models on structural MRI data: an SZ-HC model based on 70 schizophrenia patients and 74 controls and a BA model (based on 561 healthy individuals, age range = 66 years). We then investigated the two models' predictions in the naturalistic longitudinal Northern Finland Birth Cohort 1966 (NFBC1966) following 29 schizophrenia and 61 controls for nine years. The SZ-HC model's schizophrenia-specificity was further assessed by utilizing independent validation (62 schizophrenia, 95 controls) and depression samples (203 depression, 203 controls). We found better performance at the NFBC1966 follow-up (sensitivity = 75.9%, specificity = 83.6%) compared to the baseline (sensitivity = 58.6%, specificity = 86.9%). This finding resulted from progression in disorder-specific pattern expression in schizophrenia and was not explained by concomitant acceleration of brain aging. The disorder-specific pattern's progression reflected longitudinal changes in cognition, outcomes, and local brain changes, while BA captured treatment-related and global brain alterations. The SZ-HC model was also generalizable to independent schizophrenia validation samples but classified depression as control subjects. Our research underlines the importance of taking account of longitudinal progression in a disorder-specific pattern in schizophrenia when developing ML classifiers for different age groups

O8.5. SIGNS OF ADVERSITY - A NOVEL MACHINE LEARNING APPROACH TO CHILDHOOD TRAUMA, BRAIN STRUCTURE AND CLINICAL PROFILES

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Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness

Cognitively impaired and spared patient subgroups were identified in psychosis and depression, and in clinical high-risk for psychosis (CHR). Studies suggest differences in underlying brain structural and functional characteristics. It is unclear whether cognitive subgroups are transdiagnostic phenomena in early stages of psychotic and affective disorder which can be validated on the neural level. Patients with recent-onset psychosis (ROP; N = 140; female = 54), recent-onset depression (ROD; N = 130; female = 73), CHR (N = 128; female = 61) and healthy controls (HC; N = 270; female = 165) were recruited through the multi-site study PRONIA. The transdiagnostic sample and individual study groups were clustered into subgroups based on their performance in eight cognitive domains and characterized by gray matter volume (sMRI) and resting-state functional connectivity (rsFC) using support vector machine (SVM) classification. We identified an impaired subgroup (NROP = 79, NROD = 30, NCHR = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (all p < 0.001). A spared subgroup (NROP = 61, NROD = 100, NCHR = 91) performed comparable to HC. Single-disease subgroups indicated that cognitive impairment is stronger pronounced in impaired ROP compared to impaired ROD and CHR. Subgroups in ROP and ROD showed specific symptom- and functioning-patterns. rsFC showed superior accuracy compared to sMRI in differentiating transdiagnostic subgroups from HC (BACimpaired = 58.5%; BACspared = 61.7%, both: p < 0.01). Cognitive findings were validated in the PRONIA replication sample (N = 409). Individual cognitive subgroups in ROP, ROD and CHR are more informative than transdiagnostic subgroups as they map onto individual cognitive impairment and specific functioning- and symptom-patterns which show limited overlap in sMRI and rsFC. Clinical trial registry name: German Clinical Trials Register (DRKS). Clinical trial registry URL: https://www.drks.de/drks_web/. Clinical trial registry number: DRKS00005042

The impact of visual dysfunctions in recent-onset psychosis and clinical high-risk state for psychosis.

Subtle subjective visual dysfunctions (VisDys) are reported by about 50% of patients with schizophrenia and are suggested to predict psychosis states. Deeper insight into VisDys, particularly in early psychosis states, could foster the understanding of basic disease mechanisms mediating susceptibility to psychosis, and thereby inform preventive interventions. We systematically investigated the relationship between VisDys and core clinical measures across three early phase psychiatric conditions. Second, we used a novel multivariate pattern analysis approach to predict VisDys by resting-state functional connectivity within relevant brain systems. VisDys assessed with the Schizophrenia Proneness Instrument (SPI-A), clinical measures, and resting-state fMRI data were examined in recent-onset psychosis (ROP, n = 147), clinical high-risk states of psychosis (CHR, n = 143), recent-onset depression (ROD, n = 151), and healthy controls (HC, n = 280). Our multivariate pattern analysis approach used pairwise functional connectivity within occipital (ON) and frontoparietal (FPN) networks implicated in visual information processing to predict VisDys. VisDys were reported more often in ROP (50.34%), and CHR (55.94%) than in ROD (16.56%), and HC (4.28%). Higher severity of VisDys was associated with less functional remission in both CHR and ROP, and, in CHR specifically, lower quality of life (Qol), higher depressiveness, and more severe impairment of visuospatial constructability. ON functional connectivity predicted presence of VisDys in ROP (balanced accuracy 60.17%, p = 0.0001) and CHR (67.38%, p = 0.029), while in the combined ROP + CHR sample VisDys were predicted by FPN (61.11%, p = 0.006). These large-sample study findings suggest that VisDys are clinically highly relevant not only in ROP but especially in CHR, being closely related to aspects of functional outcome, depressiveness, and Qol. Findings from multivariate pattern analysis support a model of functional integrity within ON and FPN driving the VisDys phenomenon and being implicated in core disease mechanisms of early psychosis states

Pattern of predictive features of continued cannabis use in patients with recent-onset psychosis and clinical high-risk for psychosis.

Continued cannabis use (CCu) is an important predictor for poor long-term outcomes in psychosis and clinically high-risk patients, but no generalizable model has hitherto been tested for its ability to predict CCu in these vulnerable patient groups. In the current study, we investigated how structured clinical and cognitive assessments and structural magnetic resonance imaging (sMRI) contributed to the prediction of CCu in a group of 109 patients with recent-onset psychosis (ROP). We tested the generalizability of our predictors in 73 patients at clinical high-risk for psychosis (CHR). Here, CCu was defined as any cannabis consumption between baseline and 9-month follow-up, as assessed in structured interviews. All patients reported lifetime cannabis use at baseline. Data from clinical assessment alone correctly classified 73% (p  0.093), and their addition to the interview-based predictor via stacking did not improve prediction significantly, either in the ROP or CHR groups (ps > 0.065). Lower functioning, specific substance use patterns, urbanicity and a lack of other coping strategies contributed reliably to the prediction of CCu and might thus represent important factors for guiding preventative efforts. Our results suggest that it may be possible to identify by clinical measures those psychosis-spectrum patients at high risk for CCu, potentially allowing to improve clinical care through targeted interventions. However, our model needs further testing in larger samples including more diverse clinical populations before being transferred into clinical practice

A multivariate neuromonitoring approach to neuroplasticity-based computerized cognitive training in recent onset psychosis

Two decades of studies suggest that computerized cognitive training (CCT) has an effect on cognitive improvement and the restoration of brain activity. Nevertheless, individual response to CCT remains heterogenous, and the predictive potential of neuroimaging in gauging response to CCT remains unknown. We employed multivariate pattern analysis (MVPA) on whole-brain resting-state functional connectivity (rsFC) to (neuro)monitor clinical outcome defined as psychosis-likeness change after 10-hours of CCT in recent onset psychosis (ROP) patients. Additionally, we investigated if sensory processing (SP) change during CCT is associated with individual psychosis-likeness change and cognitive gains after CCT. 26 ROP patients were divided into maintainers and improvers based on their SP change during CCT. A support vector machine (SVM) classifier separating 56 healthy controls (HC) from 35 ROP patients using rsFC (balanced accuracy of 65.5%,P < 0.01) was built in an independent sample to create a naturalistic model representing the HC-ROP hyperplane. This model was out-of-sample cross-validated in the ROP patients from the CCT trial to assess associations between rsFC pattern change, cognitive gains and SP during CCT. Patients with intact SP threshold at baseline showed improved attention despite psychosis status on the SVM hyperplane at follow-up (p < 0.05). Contrarily, the attentional gains occurred in the ROP patients who showed impaired SP at baseline only if rsfMRI diagnosis status shifted to the healthy-like side of the SVM continuum. Our results reveal the utility of MVPA for elucidating treatment response neuromarkers based on rsFC-SP change and pave the road to more personalized interventions

Training infection control and hospital hygiene professionals in Europe, 2010 : agreed core competencies among 33 European countries

The harmonisation of training programmes for infection control and hospital hygiene (IC/HH) professionals in Europe is a requirement of the Council recommendation on patient safety. The European Centre for Disease Prevention and Control commissioned the ‘Training Infection Control in Europe’ project to develop a consensus on core competencies for IC/HH professionals in the European Union (EU). Core competencies were drafted on the basis of the Improving Patient Safety in Europe (IPSE) project’s core curriculum (CC), evaluated by questionnaire and approved by National Representatives (NRs) for IC/HH training. NRs also re-assessed the status of IC/HH training in European countries in 2010 in comparison with the situation before the IPSE CC in 2006. The IPSE CC had been used to develop or update 28 of 51 IC/HH courses. Only 10 of 33 countries offered training and qualification for IC/ HH doctors and nurses. The proposed core competencies are structured in four areas and 16 professional tasks at junior and senior level. They form a reference for standardisation of IC/HH professional competencies and support recognition of training initiatives.peer-reviewe