Prefrontal dopamine D1 receptors and working memory in schizotypal personality disorder: a PET study with [¹¹C]NNC112.
BACKGROUND
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.


OBJECTIVE
The aim of this study was to characterize prefrontal D1 receptor availability and its relation to WM performance in SPD.


METHODS
We used positron emission tomography (PET) and the radiotracer [(11)C]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 (r s  = -0.551, p = .022 and r s  = -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 alterations in prefrontal D1 receptor availability. 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.
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA, judy.thompson@rutgers.edu.
Judy L
JL
Thompson
Daniel R
DR
Rosell
Mark
M
Slifstein
Ragy R
RR
Girgis
Xiaoyan
X
Xu
Yosefa
Y
Ehrlich
Lawrence S
LS
Kegeles
Erin A
EA
Hazlett
Anissa
A
Abi-Dargham
Larry J
LJ
Siever
D000328:Adult; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism; D011877:Radionuclide Imaging; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D012569:Schizotypal Personality Disorder / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000523:psychology
D017447:Receptors, Dopamine D1; D004298:Dopamine