Extrastriatal dopamine D_2/3 receptors and cortical grey matter volumes in antipsychotic-naïve schizophrenia patients before and after initial antipsychotic treatment

Abstract

Objectives: Long-term dopamine D_2/3 receptor blockade, common to all antipsychotics, may underlie progressive brain volume changes observed in patients with chronic schizophrenia. In the present study, we examined associations between cortical volume changes and extrastriatal dopamine D_2/3 receptor binding potentials (BP_ND) in first-episode schizophrenia patents at baseline and after antipsychotic treatment.

Methods: Twenty-two initially antipsychotic-naïve patients underwent magnetic resonance imaging (MRI), [¹²³I]epidepride single-photon emission computerised tomography (SPECT), and psychopathology assessments before and after 3 months of treatment with either risperidone (N = 13) or zuclopenthixol (N = 9). Twenty healthy controls matched on age, gender and parental socioeconomic status underwent baseline MRI and SPECT.

Results: Neither extrastriatal D_2/3 receptor BP_ND at baseline, nor blockade at follow-up, was related to regional cortical volume changes. In post-hoc analyses excluding three patients with cannabis use we found that higher D_2/3 receptor occupancy was significantly associated with an increase in right frontal grey matter volume.

Conclusions: The present data do not support an association between extrastriatal D_2/3 receptor blockade and extrastriatal grey matter loss in the early phases of schizophrenia. Although inconclusive, our exclusion of patients tested positive for cannabis use speaks to keeping attention to potential confounding factors in imaging studies.

Keywords:

• Schizophrenia
• antipsychotic-naïve
• frontal dopamine D2/3-receptor
• grey matter volume
• psychopathology

Acknowledgements

We thank Dr. Brian V. Broberg, Bente Dall, and Eva Broedsgaard for technical assistance.

Disclosure statement

Dr. Glenthøj is the leader of Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS). CINS is partially funded by an independent grant from the Lundbeck Foundation based in international review (R25-A2701). Additionally, the study has obtained financial support from the Danish Medical Research Council, Mental Health Services in the Capital Region of Denmark, H:S (Copenhagen Hospital Cooperation) Research Council, and a non-restricted grant from Janssen-Cilag A/S and the Novo Nordic Foundation. None of the parties sponsoring the study had any role in the design or conduct of the study, nor in collection, management, analysis, or interpretation of data, nor in preparation, review or approval of the manuscript.

Dr. Ebdrup has received lecture fees from Bristol-Myers Squibb, Otsuka Pharma Scandinavia AB, and Eli Lilly Company and is part of the Advisory Board of Eli Lilly Danmark A/S, Janssen-Cilag, and Takeda Pharmaceutical Company Ltd. All other authors declare no conflict of interest.