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Striatal dopamine release in schizophrenia comorbid with substance dependence

Molecular Psychiatry volume 18, pages 909–915 (2013)Cite this article

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Abstract

Dopamine (DA) has a role in the pathophysiology of schizophrenia and addiction. Imaging studies have indicated that striatal DA release is increased in schizophrenia, predominantly in the precommissural caudate (preDCA), and blunted in addiction, mostly in the ventral striatum (VST). Therefore, we aimed to measure striatal DA release in patients with comorbid schizophrenia and substance dependence. We used [11C]raclopride positron emission tomography and an amphetamine challenge to measure baseline DA D2-receptor availability (BPND) and its percent change post-amphetamine (ΔBPND, to index amphetamine-induced DA release) in striatal subregions in 11 unmedicated, drug-free patients with both schizophrenia and substance dependence, and 15 healthy controls. There were no significant group differences in baseline BPND. Linear mixed modeling using ΔBPND as the dependent variable and striatal region of interest as a repeated measure indicated a significant main effect of diagnosis, F(1, 24)=8.38, P=0.008, with significantly smaller ΔBPND in patients in all striatal subregions (all P⩽0.04) except VST. Among patients, change in positive symptoms after amphetamine was significantly associated with ΔBPND in the preDCA (rs=0.69, P=0.03) and VST (rs=0.64, P=0.05). In conclusion, patients with comorbid schizophrenia and substance dependence showed significant blunting of striatal DA release, in contrast to what has been found in schizophrenia without substance dependence. Despite this blunting, DA release was associated with the transient amphetamine-induced positive-symptom change, as observed in schizophrenia. This is the first description of a group of patients with schizophrenia who display low presynaptic DA release, yet show a psychotic reaction to increases in D2 stimulation, suggesting abnormal postsynaptic D2 function.

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Acknowledgements

We thank the research participants of this study and express gratitude for the expert assistance of Beatriz Alvarez, Rawad Ayoub, Jennifer Bae, Felipe Castillo, John Castrillon, Ray Goetz, Elizabeth Hackett, Deborah Hasin, Olga Kambalov, Olga Medina, Elizabeth Raggi and Sharon Samet. This work was supported by a grant from the National Institute on Drug Abuse [R21 DA023039-01] to Anissa Abi-Dargham.

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  1. J L Thompson and N Urban: joint first authors.

Authors and Affiliations

  1. Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA

    J L Thompson, N Urban, M Slifstein, X Xu, L S Kegeles, R R Girgis, Y Beckerman, J M Harkavy-Friedman, R Gil & A Abi-Dargham

  2. Department of Radiology, Columbia University College of Physicians and Surgeons, New York, NY, USA

    L S Kegeles & A Abi-Dargham

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Correspondence to J L Thompson.

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Thompson, J., Urban, N., Slifstein, M. et al. Striatal dopamine release in schizophrenia comorbid with substance dependence. Mol Psychiatry 18, 909–915 (2013). https://doi.org/10.1038/mp.2012.109

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