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Neuropsychopharmacology
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Paranoid Schizophrenia is Characterized by Increased CB1 Receptor Binding in the Dorsolateral Prefrontal Cortex

Neuropsychopharmacologyvolume 36pages1620–1630 (2011)Cite this article

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Abstract

A number of studies suggest a dysregulation of the endogenous cannabinoid system in schizophrenia (SCZ). In the present study, we examined cannabinoid CB1 receptor (CB1R) binding and mRNA expression in the dorsolateral prefrontal cortex (DLPFC) (Brodmann's area 46) of SCZ patients and controls, post-mortem. Receptor density was investigated using autoradiography with the CB1R ligand [3H] CP 55 940 and CB1R mRNA expression was measured using quantitative RT-PCR in a cohort of 16 patients with paranoid SCZ, 21 patients with non-paranoid SCZ and 37 controls matched for age, post-mortem interval and pH. All cases were obtained from the University of Sydney Tissue Resource Centre. Results were analyzed using one-way analysis of variance (ANOVA) andpost hoc Bonferroni tests and with analysis of covariance (ANCOVA) to control for demographic factors that would potentially influence CB1R expression. There was a main effect of diagnosis on [3H] CP 55 940 binding quantified across all layers of the DLPFC (F(2,71)=3.740,p=0.029).Post hoc tests indicated that this main effect was due to patients with paranoid SCZ having 22% higher levels of CB1R binding compared with the control group. When ANCOVA was employed, this effect was strengthened (F(2,67)=6.048,p=0.004) with paranoid SCZ patients differing significantly from the control (p=0.004) and from the non-paranoid group (p=0.016). In contrast, no significant differences were observed in mRNA expression between the different disease subtypes and the control group. Our findings confirm the existence of a CB1R dysregulation in SCZ and underline the need for further investigation of the role of this receptor particularly in those diagnosed with paranoid SCZ.

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Acknowledgements

This work was supported by the Schizophrenia Research Institute, utilizing infrastructure funding from New South Wales Health, the Macquarie Group Foundation, Neuroscience Research Australia, and the University of New South Wales. Tissues were received from the New South Wales Tissue Resource Centre at the University of Sydney, which is supported by the National Health and Medical Research Council of Australia, Schizophrenia Research Institute, National Institute of Alcohol Abuse and Alcoholism (NIH (NIAAA) R24AA012725). We thank Nina Sundqvist of the New South Wales Tissue Resource Centre for her assistance.

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Authors and Affiliations

  1. ANSTO Life Sciences, Australian Nuclear Science and Technology Organization, Sydney, New South Wales, Australia

    Victoria S Dalton & Katerina Zavitsanou

  2. Schizophrenia Research Institute, Sydney, New South Wales, Australia

    Victoria S Dalton, Leonora E Long, Cyndi Shannon Weickert & Katerina Zavitsanou

  3. Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, New South Wales, Australia

    Leonora E Long & Cyndi Shannon Weickert

  4. School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia

    Leonora E Long

  5. School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia

    Cyndi Shannon Weickert

Authors
  1. Victoria S Dalton
  2. Leonora E Long
  3. Cyndi Shannon Weickert
  4. Katerina Zavitsanou

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Correspondence toKaterina Zavitsanou.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on the Neuropsychopharmacology website

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Dalton, V., Long, L., Weickert, C.et al. Paranoid Schizophrenia is Characterized by Increased CB1 Receptor Binding in the Dorsolateral Prefrontal Cortex.Neuropsychopharmacol36, 1620–1630 (2011). https://doi.org/10.1038/npp.2011.43

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