Do neurological soft signs in at-risk mental state individuals predict transition to first episode psychosis? Corinne Tamagni1, PhD; Erich Studerus1, PhD; Ute Gschwandtner2, MD; Anna Walter1, MD; Charlotte Rapp1, MSc; Hilal Bugra1, MSc; Anita Riecher-Rössler1, MD 1University of Basel Psychiatric Clinics, Switzerland 2University Hospital Basel, Switzerland Background Neurological soft signs (NSS) are minor abnormalities in sensory integration, motor coordination and sequencing of complex motor acts (Heinrichs and Buchanan, 1988). They are more common in first episode psychosis (FEP) patients and in nonpsychotic genetically high-risk individuals than in healthy controls (King, et al., 1991; Rossi, et al., 1990; Lawrie, et al., 2001). Some authors have proposed them as a measurable manifestation of neurodevelopmental dysfunction and a trait-marker for psychosis proneness (Peralta et al., 2011). Aims and Hypotheses The main goal of our study was to assess NSS frequency in at-risk mental state individuals who made the transition to psychosis (ARMS-T) as compared to a group of neuroleptic-naïve FE. Supporting a neurodevelopmental model of NSS, we expected to observe no difference between these two groups. Our secondary goal was to test the sensitivity of NSS as a predictor for transition to psychosis by comparing individuals at-risk who made the transition to psychosis and those who did not (ARMS-T vs. ARMS-NT). Method 53 ARMS individuals (16 ARMS-T, 37 ARMS-NT) and 25 FE patients were examined in the framework of the Fepsy-study, which is a prospective clinical study for the early detection of psychosis (Riecher-Rössler, et al., 2009). All individuals potentially at risk (At-Risk Mental State) for developing a psychotic disorder were identified by using the Basel Screening Instrument for Psychosis (BSIP) (Riecher-Rössler, et al., 2008) and followed-up at regular intervals for up to 7 or until transition to psychosis with the aim of detecting actual transition to psychosis. Neurological soft signs were assessed using the modified and shortened version of the Neurological Evaluation Scale (NES) (Sanders et al., 1998) originally developed by Heinrichs & Buchanan (1988). This scale measures four domains: sensory integration, motor coordination, sequencing of complex motor acts and other soft signs. Each item is rated 0 (no NSS), 1 (mild) or 2 (severe). Results An univariate analysis of covariance with group (ARMS-NT, ARMS-T und FE) as between-subjects factor, total NSS score (log transformed) as dependent variable and sex and age as covariates revealed no significant differences in the NSS total score neither between ARMS-NT, ARMS-T and FE (F(2,78)=1.90, p=0.16) nor between ARMS-NT and ARMS-T analysed alone (F(1, 53)=3.87, p=0.06). Sex and age did not differ between groups. Also when examining the four sub-scores separately using Kruskal-Wallis tests we found no significant differences between our three groups (Table 1). ARMS-NT ARMS-T FE ARMS-T vs. ARMS-NT vs. FE ARMS-T vs. ARMS-FE ARMS-T vs. ARMS-NT Sensory integration   27% 12% 24% p=0.48 p= 0.31 p=0.23 Motor coordination 3% 0% 4% p=0.74 p=0.42 p=0.51 Sequencing of complex motor acts 28% 6% p= 0.20 p=0.12 p=0.07 Other 16% 8% p= 0.62 p=0.67 NSS pathology (total) 49% 31% 36% p= 0.19 Table 1 ARMS-NT, ARMS-T and FE displaying at least one neurological soft sign (mild or severe) for each domain and overall. Summary and Conclusions Taken together our analyses revealed (1) no significant difference between individuals at-risk and first episode psychosis patients (2) similar frequency of NSS in ARMS who later made the transition to psychosis and in those who did not, and (3) relative low rates of NSS. Our findings thus provide further support to the proposed neurodevelopmental model of NSS and confirm the hypothesis that NSS may be a sign of deviant brain development. However, they also suggest that the predictive value of NSS for a transition to psychosis is poor. NSS may be a nonspecific indicator of neurodevelopmental dysfunction. They may be present only in a subgroup of patients with a strong neurodevelopmental basis of their disorder. The fact they are present also in a high percentage of patients with an at-risk mental state for psychosis without transition to frank psychosis, might indicate that also these patients have a neurodevelopmental predisposition for their symptoms. References Heinrichs, D., & Buchanan, R. (1988). Significance and meaning of neurological signs in schizophrenia. Am J Psychiatry, 145(1), 11-18. King, D. J., Wilson, A., Cooper, S. J., & Waddington, J. L. (1991). The clinical correlates of neurological soft signs in chronic schizophrenia. The British Journal of Psychiatry, 158(6), 770-775. Lawrie, S. M., Byrne, M., Miller, P., Hodges, A., Clafferty, R. A., Owens, D. G. C., & Johnstone, E. C. (2001). 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Rossi, A., De Cataldo, S., Di Michele, V., Manna, V., Ceccoli, S., Stratta, P., & Casacchia, M. (1990). Neurological soft signs in schizophrenia. The British Journal of Psychiatry, 157(5), 735-739. Sanders, R. D., Forman, S. D., Pierri, J. N., Baker, R. W., Kelley, M. E., Van Kammen, D. P., & Keshavan, M. S. (1998). Inter-rater reliability of the neurological examination in schizophrenia. Schizophrenia Research, 29(3), 287-292. Disclosure A.R.-R., A.W. and C. T. were supported by a grant by the Swiss National Science Foundation (SNF). A.R.-R. and C.R. were supported by a grant by the EU for the “European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) . A.R.-R. and H.B. were supported by the Stanley Foundation for the Neurapro-E (North America Europe Australia Prodrome) Study. Contact PhD Corinne Tamagni / corinne.tamagni@upkbs.ch