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Rationale Schizotypal personality disorder (SPD) is associated with working memory (WM) impairments that are similar to those observed in schizophrenia. Imaging studies have suggested that schizophrenia is associated with alterations in dopamine D1-receptor availability in the prefrontal cortex (PFC) that may be related to the WM impairments that characterize this disorder. Objectives To characterize prefrontal D1-receptor availability and its relation to WM performance in SPD. Methods We used positron emission tomography (PET) and the radiotracer [11C]NNC112 with 18 unmedicated SPD and 21 healthy-control participants; as an index of D1-receptor availability, binding-potential (BP) measures (BPF, BPND, and BPP) were calculated for prefrontal and striatal subregions. To assess WM, SPD participants completed the 2-back and Paced Auditory Serial Addition Test (PASAT). Results There were no significant group differences in PFC BP. BPF and BPP in the medial PFC were significantly negatively related to PASAT performance (rs=-0.551, p=.022 and rs=-0.488, p=.047, respectively), but BP was not related to 2-back performance. Conclusions In contrast to what has been found in schizophrenia, SPD was not associated with significant prefrontal D1-receptor alterations. Similar to previous schizophrenia findings, however, higher prefrontal D1-receptor availability was associated with poorer WM performance (as measured by the PASAT) in SPD. These findings suggest that schizophrenia and SPD may share a common pathophysiological feature related to prefrontal dopamine functioning that contributes to WM dysfunction, but that in SPD, alterations in D1 may occur only in a subset of individuals and/or to an extent that is minor relative to what occurs in schizophrenia.

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