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WC5D PREPULSE INHIBITION AND P50 GATING IN THE PRODROME AND FIRST EPISODE OF SCHIZOPHRENIA
Symposium 5: Neurobiological markers of risk for psychosis Duesseldorf, Germany, 4 Department of Psychiatry, University of Munich, Munich, Germany Presenting author contact: [email protected] Introduction: Event-related potential (ERP) alterations, most notably the P300 component, are among the most robust trait markers for schizophrenia and should therefore be useful for improving prediction in clinical high risk groups. Methods: ERPs elicited during an auditory oddball task were investigated in young adult subjects with a high risk to develop schizophrenia (n = 100) and a group of matched healthy controls (n = 40). High-risk participants were either in a putative early prodromal stage, defined by the presence of predictive basic symptoms, or in a late prodromal state, mainly defined by attenuated positive symptoms or by brief limited intermittent psychotic symptoms. Results: Subjects clinically at risk for schizophrenia had auditory P300 amplitude abnormalities over the left posterior temporal and parietal sites compared to controls, resembling reported abnormalities in schizotypal personality disorder, first-episode and chronic schizophrenia. Deficits were more pronounced in individuals with an affected first-degree relative and were correlated with verbal memory performance. Patients in a presumed late prodromal stage also showed frontal P300 amplitude reductions. Frontal P300 was lower in subjects going on to develop a psychotic disorder within 12 month. Discussion: Our results support the hypothesis of a left posterior temporal P300 abnormality as an indicator of (genetic) susceptibility to schizophrenia. Frontal P300 amplitude reductions may reflect the impending onset of disorder. While the incremental predictive power of these ERP measures over clinical measures will have to be further established, the results do already validate the current clinical high risk definitions. WC5C AUDITORY EVOKED POTENTIALS IN INDIVIDUALS AT RISK DEVELOPING A PSYCHOSIS, IN FIRST EPISODE PATIENTS AND THOSE WITH CHRONIC SCHIZOPHRENIA A. Brockhaus-Dumke1 *, S. Ruhrmann1 , C. Hoppmann1 , W. W¨olver3 , J. Brinkmeyer3 , M. Wagner2 , I. Frommann2 , J. Klosterk¨otter1 . 1 University of Cologne, Cologne, Germany, 2 University of Bonn, Bonn, Germany, 3 University of Duesseldorf, Duesseldorf, Germany Presenting author contact: [email protected] The Early Recognition and Intervention Center (FETZ) at the Department of Psychiatry and Psychotherapy of the University of Cologne/Germany aims to evaluate individuals in the prodromal phase (at-risk group) to improve strategies of early recognition and intervention. Abnormalities in auditory information processing are frequently reported in schizophrenia patients. As part of a multidimensional approach to the early recognition of psychosis, P50 and N100 derived sensory gating indices, mismatch negativity (MMN) and P300 reflecting different aspects of auditory information processing were investigated for their qualification as a neurobiological at-risk indicator of psychosis. We will present auditory evoked ERP/EEG data obtained from subjects with prodromal symptoms already having developed a psychosis (PP), subjects with a first episode of schizophrenia (FE) and subjects with multiple episodes (ME).
S13 Our data suggest that deficits in sensory gating (double click paradigm) and echoic memory (mismatch negativity) are most prominent in ME patients. Only a gradual, but non-significant decline was present in PP and FE patients. In contrast to these paradigms reflecting predominantly preattentive processes, the P300 data reflecting higher cognitive functions show significant reduction not only in ME patients, but also in FE patients and PP patients. These findings suggest that auditory evoked potentials, especially the P300, may provide a risk marker. Preliminary follow-up data of individuals at risk being assessed before and after transition to psychosis will be presented. The significance of these results for subsequent conversion to psychosis, and the potential role for ERP measures in enhancing risk prediction in clinical high risk subjects will be discussed. WC5D PREPULSE INHIBITION AND P50 GATING IN THE PRODROME AND FIRST EPISODE OF SCHIZOPHRENIA K.S. Cadenhead *. University of California San Diego, La Jolla, CA, United States Presenting author contact: [email protected] Introduction: The Cognitive Assessment and Risk Evaluation (CARE) Program at UCSD aims to identify and assess individuals in the prodromal phase (at risk group) and in the first episode of schizophrenia using potential vulnerability markers for schizophrenia. Early identification can lead to early intervention and potentially prevention of the illness. An additional aim is to increase understanding of the neurodevelopmental changes in the early phase of the illness. Method: At risk (N = 55), first episode (N = 22) and normal subjects (N = 36) were assessed using prepulse inhibition (PPI) of the startle response and P50 event related potential gating in a longitudinal design. Results: While there were no deficits in baseline PPI in the at-risk and first episode samples compared to normals, deficits were apparent at 1 year follow-up. Intraclass correlation coefficients demonstrated stability of PPI. The normals had the most stability, followed by the at-risk and finally the first episode subjects. The first episode group and at-risk subjects with a first degree relative with schizophrenia, had deficits in P50 gating consistent with previous observations in schizotypal personality disorder (SPD). The two measures (P50 and PPI) were negatively correlated (r = −0.32) in a sample of 30 at-risk subjects, suggesting a divergence of measures, similar to findings of a lack of association between the two measures of inhibitory processing in SPD. Discussion: Although PPI has been found to be stable in both normal populations and chronic schizophrenia, it is possible that this measure is less stable in the early stages of the illness due to the rapidly evolving brain changes that can possibly be indexed by PPI. Replication of the interesting divergent pattern of PPI and P50 in at-risk subjects suggests that the two measures identify separable neurobiological functions with potentially different pathophysiologies and associated genetic architecture, symptoms and outcome profiles.
S13 Our data suggest that deficits in sensory gating (double click paradigm) and echoic memory (mismatch negativity) are most prominent in ME patients. Only a gradual, but non-significant decline was present in PP and FE patients. In contrast to these paradigms reflecting predominantly preattentive processes, the P300 data reflecting higher cognitive functions show significant reduction not only in ME patients, but also in FE patients and PP patients. These findings suggest that auditory evoked potentials, especially the P300, may provide a risk marker. Preliminary follow-up data of individuals at risk being assessed before and after transition to psychosis will be presented. The significance of these results for subsequent conversion to psychosis, and the potential role for ERP measures in enhancing risk prediction in clinical high risk subjects will be discussed. WC5D PREPULSE INHIBITION AND P50 GATING IN THE PRODROME AND FIRST EPISODE OF SCHIZOPHRENIA K.S. Cadenhead *. University of California San Diego, La Jolla, CA, United States Presenting author contact: [email protected] Introduction: The Cognitive Assessment and Risk Evaluation (CARE) Program at UCSD aims to identify and assess individuals in the prodromal phase (at risk group) and in the first episode of schizophrenia using potential vulnerability markers for schizophrenia. Early identification can lead to early intervention and potentially prevention of the illness. An additional aim is to increase understanding of the neurodevelopmental changes in the early phase of the illness. Method: At risk (N = 55), first episode (N = 22) and normal subjects (N = 36) were assessed using prepulse inhibition (PPI) of the startle response and P50 event related potential gating in a longitudinal design. Results: While there were no deficits in baseline PPI in the at-risk and first episode samples compared to normals, deficits were apparent at 1 year follow-up. Intraclass correlation coefficients demonstrated stability of PPI. The normals had the most stability, followed by the at-risk and finally the first episode subjects. The first episode group and at-risk subjects with a first degree relative with schizophrenia, had deficits in P50 gating consistent with previous observations in schizotypal personality disorder (SPD). The two measures (P50 and PPI) were negatively correlated (r = −0.32) in a sample of 30 at-risk subjects, suggesting a divergence of measures, similar to findings of a lack of association between the two measures of inhibitory processing in SPD. Discussion: Although PPI has been found to be stable in both normal populations and chronic schizophrenia, it is possible that this measure is less stable in the early stages of the illness due to the rapidly evolving brain changes that can possibly be indexed by PPI. Replication of the interesting divergent pattern of PPI and P50 in at-risk subjects suggests that the two measures identify separable neurobiological functions with potentially different pathophysiologies and associated genetic architecture, symptoms and outcome profiles.