Dopamine D2 and D3 binding in people at clinical high risk for schizophrenia, antipsychotic-naive patients and healthy controls while performing a cognitive task

Dopamine D2 and D3 binding in people at clinical high risk for schizophrenia, antipsychotic-naive patients and healthy controls while performing a cognitive task

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J Psychiatry Neurosci 2013; 38(2):98-106

Ivonne Suridjan, HBSc; Pablo Rusjan, PhD; Jean Addington, PhD; Alan A. Wilson, PhD; Sylvain Houle, MD, PhD; Romina Mizrahi, MD, PhD

Suridjan, Rusjan, Wilson, Houle, Mizrahi — PET Centre, Centre for Addiction and Mental Health, Toronto, Ont.; Addington — Department of Psychiatry, University of Calgary, Calgary, Alta.; Wilson, Houle, Mizrahi — Department of Psychiatry, University
of Toronto, Toronto, Ont.

Abstract

Background: The dopamine (DA) D2 receptors exist in 2 states: a high-affinity state (D2 high ) that is linked to second messenger systems, responsible for functional effects, exhibits high affinity for agonists (e.g., DA), and a low-affinity state that is functionally inert exhibits lower affinity for agonists. The DA D3 receptor subtype exhibits high agonist affinity, whereas the existence of the multiple affinity states is controversial. Preclinical studies in animal models of psychosis have shown a selective increase of D2 high as the common factor in psychosis, and the D3 receptor has been suggested to be involved in the pathophysiology of schizophrenia.

Methods: We studied D2 high and D3 in people at clinical high risk (CHR) for schizophrenia and in antipsychotic-naive patients with schizophrenia using the novel positron emission tomography radiotracer, [11 C]-(+)-PHNO. The binding potential nondisplaceable (BPND ) was examined in the regions of interest (ROI; caudate, putamen, ventral striatum, globus pallidus, substantia nigra and thalamus) using an ROI and a voxel-wise approach while participants performed a cognitive task.

Results: We recruited 12 CHR individuals and 13 antipsychotic-naive patients with schizophreniaspectrum disorder, whom we compared with 12 age- and sex-matched healthy controls. The BPND between patients and controls did not differ in any of the ROIs, consistent with the voxel-wise analysis. Correlations between the BPND in D3 -rich regions and psychopathology warrant further investigation.

Limitations: In the absence of resting-state (baseline) BPND data, or following a depletion paradigm (i.e., α-methyl partyrosine), it is not possible to ascertain whether the lack of difference among the groups is owing to different levels of baseline DA or to release during the cognitive task.

Conclusion: To our knowledge, the present study represents the first effort to measure the D2 and D3 receptors under a cognitive challenge in individuals putative/prodromal for schizophrenia using [11 C]-(+)-PHNO.


Submitted Nov. 22, 2011; Revised Apr. 2, June 7, 2012; Accepted June 11, 2012.

Acknowledgments: We are grateful to Armando Garcia, Winston Stableford, Min Wong, Alvina Ng, Terry Bell, Ted Harris-Brandts and Peter Bloomfield. This work was supported by the Canadian Institutes for Health Research (CIHR). R. Mizrahi is supported by the New Investigator Award from CIHR, and the Ontario Mental Health Foundation New Investigator Fellowship.

Competing interests: None declared by I. Suridjan. P. Rusjan, A.A.Wilson and S. Houle declare CIHR funding to their institution (grant MOP-74702). P. Rusjan and R. Mizrahi are employed by the Centre for Addiction and Mental Health. J. Addington declares funding from the National Institute of Mental Health to her institution (grant U01MHO66134). As above for R. Mizrahi.

Contributors: J. Addington and R. Mizrahi designed the study. I. Suridjan and J. Addington acquired the data, which all other authors analyzed. I. Suridjan and R. Mizrahi wrote the article, which all authors reviewed and approved for publication.

Competing interests: None declared.

DOI: 10.1503/jpn.110181

Correspondence to: R. Mizrahi, PET Centre, Centre for Addiction and Mental Health, 250 College St., Toronto ON M5T 1R8; romina.mizrahi@camhpet.ca