T137. CLASSIFICATION OF RECENT-ONSET PSYCHOSIS BASED ON RESTING-STATE FUNCTIONAL CONNECTIVITY AND THE RELATIONSHIP TO NEUROCOGNITIVE IMPAIRMENT

Abstract Background Impairments in cognitive functioning are a core feature of psychotic disorders and they have been associated with resting-state functional connectivity (rsFC) alterations in patients suffering from psychosis (Dauverman et al., 2014). Multivariate pattern analysis (MVPA) has proven to be a useful tool in the investigation of rsFC alteration in psychosis and in detecting subtle differences in multidimensional data sets (Kambeitz et al., 2015). In this study, we differentiated recent-onset psychosis patients (ROP) from healthy controls (HC) using a Support Vector Machine (SVM) classification based on rsFC. Furthermore, we investigated the relationship of the discriminative rsFC pattern to neurocognitive measures. Methods Resting-state fMRI and neurocognitive measures were obtained from 220 HC and 115 ROP across 7 sites of the PRONIA consortium. The rsFC matrix was estimated for each subject by calculating pairwise correlations between mean time series of 90 brain regions based on AAL parcellation. A L1-regularized L2-loss SVM was trained to classify ROP vs. HC based on rsFC in a repeated nested cross-validation. Decision scores for ROP were correlated with cognitive measures derived from the following neuropsychological tests: Rey Auditory Verbal Learning Task (RAVLT), Phonetic and Semantic Verbal Fluency, Diagnostic Analysis of Nonverbal Accuracy, Forward and Backward Digit Span, Self-ordered Pointing Task, and Salience Attribution Test. Results The classification algorithm was able to differentiate ROP and HC with a balanced accuracy (BAC) of 71.3% based on rsFC. The discriminative connectivity pattern included short-range connections between left putamen and left hippocampus, right putamen and right caudate nucleus, left superior frontal and right inferior orbitofrontal regions, as well as long-range connections between left and right occipital cortex and left cingulate gyrus, left supramarginal gyrus and right temporal pole. Two negative correlations between the SVM decision scores for ROP and measures of the RAVLT were significant (delayed recall: r=-0.3, Bonferroni –adjusted p<.04; recall after interference: r=-0.3, Bonferroni-adjusted p<.02). Discussion The classification performance was driven by a rsFC pattern including areas involved in memory processing, such as hippocampus and cingulate gyrus (Allen et al., 2007) as well as regions related to language processing, such as the supra marginal gyrus (Li et al., 2009). The negative correlation of rsFC-based decision scores with RAVLT measures shows that patients whose verbal learning and memory is more severely impaired exhibit a more distinctive rsFC pattern than patients with less impaired verbal memory.


T136. DO VITAMIN D SUPPLEMENTATION DURING THE FIRST YEAR OF LIFE PREDICT COGNITION IN PSYCHOSES DURING MIDLIFE?
Jussi Seppälä* ,1 , Laura Tröger 2 , Erika Jääskeläinen 2 , Jouko Miettunen 2 , Matti Isdohanni 2 , Marianne Haapea 2 1 Carea, Psychiatric Services; 2 University of Oulu Background: Schizophrenia (SCZ) has been associated with cognitive impairment. The lack of vitamin D was associated with over 2-fold risk for mild cognitive impairment, and vitamin D could also associate with cognitive performance which may be explained by the role of vitamin D in the development of central nervous system or in neuroprotection. Vitamin D supplementation during the first year of life has been associated with a reduced risk of SCZ in males within the Northern Finland Birth Cohort 1966 (NFBC 1966), but no studies have examined it`s possible association with cognition in SCZ during midlife. The aim of this study was to examine the association of vitamin D supplementation during the first year of life with the cognition at the age of 43 years separately among those having psychosis and among non-psychotic controls in prospective NFBC 1966. Methods: The study is based on the NFBC 1966 concerning 12.058 liveborn children in 1966 in Northern Finland. The final study population of this study (N= 257) consisted of 60 persons with schizophrenia spectrum disorder (SSD) and of 26 individuals with non-schizophrenic psychoses (NSSD) while 171 non-psychotic participants formed the reference group. The daily dose of vitamin D was calculated based on the concentration of vitamin D in the product used and the reported amount of the product consumed. At the time when cohort was born, the recommended dose of vitamin D was 2000 IU/day. Based on maternal interviews in the year after birth, two measures of vitamin D supplementation were available: (a) frequency of intake (coded as regularly or irregularly/none) and (b) dose of vitamin D (<1600 IU/day, 1601-2000 IU/day, or >2000 IU/day. The following tests were performed at the age of 43 years: California Verbal Learning Test (CVLT), Abstraction Inhibition and Working Memory Task (AIM), Visual Object Learning Test (VOLT), Vocabulary (WAIS-III), Visual Series (WMS-III), Digit Span (WAIS-III), Grooved Pegboard, Matrix Reasoning and Verbal Fluency. Results: The study population (N= 2579 included 60 subjects with SSD, 26 persons had NSSD, and 171 non-psychotic controls formed the reference group. There were more men among those having psychosis (52.3% vs. 47.7%, respectively while the control group had more women (49.7 vs. 50.3, respectively). Only 13.2% of participants in the entire study population had received vitamin D supplementation irregularly or not at all. On the other hand, 5.1% had taken vitamin D supplementation more than the recommended dose. Because the number of those who got vitamin supplementation under recommended dose (<2000IU/day) was not more than 3 persons (1.2% of the whole study population), the association of the dose vitamin D supplements with later cognition was not analyzed. Therefore, the frequency of vitamin D supplementation (coded as regular or irregular/none) was utilized in final analyses. The frequency of vitamin D supplementation was not associated with cognition in midlife either among those having psychosis or in the control group (p-values for global cognitive performance in psychoses and controls were 0.89 and 0.61, respectively). Discussion: The main finding of this study was that no association was found between the frequency of vitamin D supplementation during first year of life and cognition in midlife either among those having psychosis or in the control group. The only earlier study (N=9.114) evaluating a link between the use of nutritional supplements during early life and risk of SCZ was carried out in NFBC 1966. In males, the use of either irregular or regular vitamin D supplements was associated with a reduced risk of SCZ compared with no supplementation.

University of Udine
Background: Impairments in cognitive functioning are a core feature of psychotic disorders and they have been associated with resting-state functional connectivity (rsFC) alterations in patients suffering from psychosis (Dauverman et al., 2014). Multivariate pattern analysis (MVPA) has proven to be a useful tool in the investigation of rsFC alteration in psychosis and in detecting subtle differences in multidimensional data sets (Kambeitz et al., 2015). In this study, we differentiated recent-onset psychosis patients (ROP) from healthy controls (HC) using a Support Vector Machine (SVM) classification based on rsFC. Furthermore, we investigated the relationship of the discriminative rsFC pattern to neurocognitive measures. Methods: Resting-state fMRI and neurocognitive measures were obtained from 220 HC and 115 ROP across 7 sites of the PRONIA consortium. The rsFC matrix was estimated for each subject by calculating pairwise correlations between mean time series of 90 brain regions based on AAL parcellation. A L1-regularized L2-loss SVM was trained to classify ROP vs. HC based on rsFC in a repeated nested cross-validation. Decision scores for ROP were correlated with cognitive measures derived from the following neuropsychological tests: Rey Auditory Verbal Learning Task (RAVLT), Phonetic and Semantic Verbal Fluency, Diagnostic Analysis of Nonverbal Accuracy, Forward and Backward Digit Span, Self-ordered Pointing Task, and Salience Attribution Test. Results: The classification algorithm was able to differentiate ROP and HC with a balanced accuracy (BAC) of 71.3% based on rsFC. The discriminative connectivity pattern included short-range connections between left putamen and left hippocampus, right putamen and right caudate nucleus, left superior frontal and right inferior orbitofrontal regions, as well as longrange connections between left and right occipital cortex and left cingulate gyrus, left supramarginal gyrus and right temporal pole. Two negative correlations between the SVM decision scores for ROP and measures of the RAVLT were significant (delayed recall: r=-0.3, Bonferroni -adjusted p<.04; recall after interference: r=-0.3, Bonferroni-adjusted p<.02). Discussion: The classification performance was driven by a rsFC pattern including areas involved in memory processing, such as hippocampus and cingulate gyrus (Allen et al., 2007) as well as regions related to language processing, such as the supra marginal gyrus (Li et al., 2009). The negative correlation of rsFC-based decision scores with RAVLT measures shows that patients whose verbal learning and memory is more severely impaired exhibit a more distinctive rsFC pattern than patients with less impaired verbal memory.

T138. ACOUSTIC PATTERNS IN SCHIZOPHRENIA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Alberto Parola* ,1 , Arndis Simonsen 2 , Vibeke Bliksted 2 , Riccardo Fusaroli 2 1 University of Turin; 2 Aarhus University Background: Individuals with schizophrenia are characterized as presenting atypical voice patterns: poverty of speech, increased pauses, distinctive pitch (mean and variability). Voice atypicalities may play a role in the social impairment experienced by patients, and could constitute a window into motor, cognitive, emotional and social components of the disorder. Indeed, they have already been generally associated with negative symptoms. However, the state of the evidence for atypical voice patterns and their relation to clinical features is uncertain. Studies using clinical rating scales indicate that voice alterations are severe across many voice properties. In contrast, quantitative acoustic studies seem to have found less robust and more variable results limited to specific features. We therefore systematically reviewed the literature quantifying acoustic patterns in schizophrenia, and performed a meta-analysis of the evidence. We aimed at identifying evidence for acoustic markers of schizophrenia and its clinical features, needs for further research and barriers to collective advancements on these issues. Methods: We adopted the "PRISMA Statement" guidelines for transparent reporting of a systematic review. The literature search was conducted on Pubmed and Google Scholar (details and pre-registration at https://goo.gl/ H1yDpm). Study selection was conducted according to the following inclusion criteria: (a) empirical study, (b) quantification of acoustic features in the vocal production of participants with schizophrenia, (c) sample including at least two individuals with schizophrenia, (d) inclusion of a comparison group, or an assessment of variation in acoustic features in relation to severity of clinical features. We identified 54 studies as eligible for inclusion and contacted all authors to obtain missing estimates and individual-level data, where possible. 34 studies availed enough information to be included in a meta-analysis. The meta-analysis consisted of mixed effects regression models, one per each relevant acoustic feature. Results: Of the 37 authors contacted, 59% responded and 5% provided at least some of the requested data. Chief reasons of denials were: i) data loss (n = 8), ii) effort required (n = 5), iii) ethical concerns with data sharing (n = 1). On the results available we found significant meta-analytic effects of schizophrenia in percentage of spoken time (n = 6, d = -1.16, 95% CIs: -2.06 -0.27) and proportion of pauses (n = 5, d = 0.56, 95% CIs: 0.15 0.96). After controlling for influential studies, we found significant differences also in pitch mean (n = 5, d = 0.40, 95% CIs: 0.12 0.68) and pitch variability (n = 6, d = -0.46, 95% CIs: -0.70 -0.23). No effects were found for pause duration (n = 7), speech rate (n = 9), speech duration (n = 5) and pitch intensity (n = 5). We found evidence for publication bias for studies investigating pause duration and pitch variability.
Key concerns on the meta-analysis are: i) small sample sizes, ii) heterogeneity of task and acoustic processing methods, iii) lack of demographic and clinical individual-level data necessary to control for confounds (e.g. medication and relation to clinical features). Discussion: We found clear effects of increased pause behavior in schizophrenia and less clear effects of pitch. However, the magnitude of these abnormalities is limited and contrast with the large effect sizes reported by studies using clinical rating scales. Future research should focus on larger sample sizes, systematic assessment of multiple acoustic features and multiple speech tasks, standardized acoustic processing methods, and individual level data available. More reflection is needed on how to make data sharing possible within privacy and ethical constraints.

T139. ELECTRORETINOGRAM ABNOMALIES IN SCHIZOPHRENIA PATIENTS WITH VISUAL HALLUCINATIONS
Vincent Laprevote* ,1 , Florent Bernardin 1 , Thomas Schwitzer 1 , Raymund Schwan 1 1 Centre Psychothérapique de Nancy Background: Retinal dysfunctions have been integrated in cognitive models of visual hallucinations in several pathologies such as Parkinsonian syndromes or eye diseases. Besides, structural abnormalities of the retinal ganglion cells are documented in schizophrenia and have been associated to visual hallucinations (VH) in neurological disorders. We aim to study functional abnormalities of retinal ganglion cells in schizophrenia patients with VH. Methods: We measured the activity of retinal ganglion cells using electroretinogram according to ISCEV criteria. We compared the amplitude and implicit time of the P50 and the N95 waves of the pattern electroretinogram in schizophrenia patients with VH (VH group, n = 7), Auditory Hallucinations or no hallucination (AH/NH group, n = 8) and controls (n = 30). Results: Preliminary findings show a significant increase of the N95 implicit time in the HV group compared with controls (p = .05). No difference was found between the HV and HA/NH groups but a gradient appeared to emerge between the 3 groups. Discussion: Functional impairment of the retinal ganglion cells appears to be more pronounced in schizophrenia patients with HV. The increase of N95 implicit time may be interpreted as a dysfunction of retinal ganglion celles rather than a cell loss. These preliminary results need to be confirmed with a larger sample.

T140. RESTING STATE NETWORKS ALTERATION IN SCHIZOPHRENIA
Gianluca Mingoia* ,1 , Igor Nenadic 2 1 RWTH Aachen University; 2 Jena University Hospital Background: While functional MRI and PET studies have shown altered task-related brain activity in schizophrenia, recent studies suggest that such differences might also be found in the resting state (RS). Here we used ICA based analysis to investigate RS fMRI data to compare connectivity of 11 well known networks (Auditory, Cerebellum, DMN, Exectutive Control, Fronto-parietal 1, Fronto-parietal 2, Salience, Sensorimotor, Visual1, Visual2, Visual3 network) between patients with schizophrenia and healthy controls suggesting deficits in related neuropsychological functions. Methods: We obtained RS fMRI series (3T, 3x3x3mm resolution, 45 slices, TR 2.55s, 210 volumes) in 25 schizophrenia patients (mean age 30a±7.3), on stable antipsychotic medication and 25 matched healthy controls (30.3a±8.6). Subjects were asked to lie in the scanner keeping eyes closed with no further specific instructions. Data were pre-processed; we applied