Metabotropic glutamate receptor mGluR2/3 and mGluR5 binding in the anterior cingulate cortex in psychotic and nonpsychotic depression, bipolar disorder and schizophrenia: implications for novel mGluR-based therapeutics

Metabotropic glutamate receptor mGluR2/3 and mGluR5 binding in the anterior cingulate cortex in psychotic and nonpsychotic depression, bipolar disorder and schizophrenia: implications for novel mGluR-based therapeutics

PDF | Appendix

J Psychiatry Neurosci 2014;39(6):407-16

Natalie Matosin, BMSc Hons; Francesca Fernandez-Enright, PhD; Elisabeth Frank, PhD; Chao Deng, PhD; Jenny Wong, PhD; Xu-Feng Huang, MD, PhD; Kelly A. Newell, PhD

Matosin, Fernandez-Enright, Frank, Deng, Wong, Huang, Newell — Faculty of Science, Medicine and Health, University of Wollongong, New South Wales; Matosin, Fernandez-Enright, Frank, Deng, Wong, Huang, Newell — Illawarra Health and Medical Research Institute, Wollongong, New South Wales; Matosin, Fernandez-Enright, Frank, Deng, Huang, Newell — Schizophrenia Research Institute, Sydney, New South Wales; Fernandez-Enright — School of Psychology, Faculty of Social Science, University of Wollongong, New South Wales, Australia

Abstract

Background: Metabotropic glutamate receptors 2/3 (mGluR2/3) and 5 (mGluR5) are novel therapeutic targets for major depression (MD), bipolar disorder (BD) and schizophrenia. We aimed to determine whether mGluR2/3 and mGluR5 binding in the anterior cingulate cortex (ACC), a brain region essential for the regulation of mood, cognition and emotion, were differentially altered in these pathologies.

Methods: Using postmortem human brains derived from 2 cohorts, [3H]LY341495 binding to mGluR2/3 and [3H]MPEP binding to mGluR5 were measured by receptor autoradiography in the ACC. The first cohort comprised samples from individuals who had MD with psychosis (MDP), MD without psychosis (MDNP) and matched controls (n = 11–12 per group). The second cohort comprised samples from individuals who had MDNP, BD, schizophrenia and matched controls (n = 15 per group).

Results: No differences in mGluR2/3 or mGluR5 binding were observed in the MDP, MDNP, BD or schizophrenia groups compared with the control group (all p > 0.05). Importantly, there were also no differences in binding densities between the psychiatric disorders (p > 0.05). We did, however, observe age-related effects, with consistent negative associations between mGluR2/3 and age in the control group (r < –0.575, p < 0.025) and the psychotic disorder groups (MDP and schizophrenia: r = –0.765 to –0.515, p < 0.05), but not in the mood disorder groups (MDNP, BD). Limitations: Replication in larger independent cohorts and medication-naive individuals would strengthen these findings.

Conclusion: Our findings suggest that mGluRs are unaltered in the ACC; however, the presence of altered receptor function cannot be discounted and requires further investigation. Taken together with previous studies, which report differential changes in mGluR2, 3 and 5 across these disorders, we suggest mGluRs may be affected in a brain region–specific manner.


Submitted Oct. 22, 2013; Revised Feb. 22, 2014; Accepted Mar. 24, 2014; Early-released June 24, 2014.

Acknowledgements: Postmortem tissue was acquired through the Stanley Medical Research Institute, who we thank for the collecting and preparing of tissue specimens. We thank the tissue donors and their families for consenting to the use of this tissue for research. N. Matosin is supported by Australian Rotary Health in the form of an Ian Scott PhD Scholarship.

Funding: This study was funded through an Illawarra Health and Medical Research Institute grant to K.A. Newell, E. Frank, C. Deng and J. Wong. This work was also supported by the Schizophrenia Research Institute, using infrastructure funding from the New South Wales Ministry of Health.

Competing interests: None declared.

Contributors: K.A. Newell designed the study. N. Matosin and K.A. Newell acquired the data, which all authors analyzed. N. Matosin and K.A. Newell wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.130242

Correspondence to: K.A. Newell, University of Wollongong, Northfields Ave., Wollongong, NSW 2522, Australia; knewell@uow.edu.au