The 5 year project will facilitate Dr. Cadenhead's further training in clinical research with a focus on developing and utilizing novel information processing measures in order to identify deficits in subjects with schizotypal personality disorder (SPD). She will receive intensive training in the use and development of two specific information processing paradigms: 1) startle plasticity measures, including the prepulse inhibition (PPI) and habituation of the startle response, and 2) measures of visual information processing, including visual backward masking (VBM) and critical stimulus duration (CSD). These information processing measures are abnormal in schizophrenia patients and are also probable biological markers for schizophrenia spectrum disorders. New paradigms will be developed and tested and the resulting startle plasticity and VBM measures will be used in SPD and schizophrenia (SZ) patients, and normal controls (NC). The new paradigms will assess 1) PPI in an attentional allocation paradigm where PPI is enhanced when attention is directed to the prepulse stimulus and 2) visual masking functions where the use of high and low spatial frequency (HSF/LSF masks tap differentially into sustained and transient neural substrates. The hypotheses are that SPD and SZ patients when compared to NC will have 1) deficits in measures of startle plasticity including the PPI and habituation of startle and 2) specific, differential deficits in LSF VBM as well as inflated CSDs, and that these new, modified paradigms will be sensitive to the hypothesized SPD deficits in startle plasticity and visual information processing. 3) It is also hypothesized that psychotic-like SPD symptoms will be associated with impairment in PPI while the social deficit SPD symptoms will be associated with greater VBM and CSD deficits in these new tasks. By using the proposed phenotypic markers for schizophrenia in a large population of non- psychotic, unmedicated SPD patients, subgroups of SPD patients with specific patterns of information processing deficits will be identified. The observed pattern of information processing deficits and specific symptom correlates in an SPD population would be an important contribution for future psychopathological and genetic-linkage studies. Mastery of these techniques and their theoretical importance will contribute to an increased understanding of the information processing deficits found in subjects at the boundaries of the schizophrenia spectrum.
| Cadenhead, K S; Serper, Y; Braff, D L (1998) Transient versus sustained visual channels in the visual backward masking deficits of schizophrenia patients. Biol Psychiatry 43:132-8 |
