334. Subcortical dopaminergic activity in schizotypal personality disorder

Abstract

Schizotypal personality disorder (SPD) patients share many genetic, phenomenological, and biologic features with schizophrenic patients, yet they do not develop the chronic psychosis associated with schizophrenia. Studies in our laboratory have shown that SPD patients demonstrate cognitive impairment in visuospatial working memory, sustained attention, and verbal learning similar, but less severe than that seen in schizophrenic patients. The administration of the dopamine-releasing agent, d-amphetamine, which can intensify psychotic symptoms in schizophrenic patients does not have this effect in SPD patients, but does produce improvement in cognitive functioning and negative symptoms. SPD patients show similar structural abnormalities to those seen in schizophrenia in reduced temporal volumes compared to controls. On the other hand, unlike schizophrenic patients, SPD patients demonstrate reduced striatal volumes on MRI and reduced striatal metabolic activity by PET compared to controls. We have thus hypothesized that the subcortical activity of SPD patients may be less “responsive” to stimulation and therefore provide a “buffer” to the development of long-term psychosis. Using a [123I] IBZM SPECT paradigm which compares dopamine displacement of IBZM from D2 receptors before and after administration of d-amphetamine, we assess the subcortical dopaminergic activity in SPD patients compared to controls. A total of 9 SPD patients have been studied to date, for comparison with data on 15 schizophrenic (SZ) patients and 15 normal controls (NC), provided by our collaborators (Abi-Dargham et al. Am J Psychiatry 155:761–767, 1998). In an interim analysis on four SPD patients, the dopamine release (expressed as % displacement) in the striatum appears to be reduced compared to the schizophrenic patients, but to be similar to normal controls (% displacement: SPD: 8.3 ± 4.5; NC: 7.3 ± 7.0; SZ: 16.7 ± 13.4). These results will be updated to include a larger cohort of SPD patients and comparison groups.