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Striatal dopamine D2 receptors in medication-naive patients with major depressive disorder as assessed with [11C]raclopride PET

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Abstract

Rationale

Among other monoamine neurotransmitters, dopamine is implicated in the pathophysiology of major depression. Experimental studies suggest the involvement of the mesolimbic dopamine system in the mechanism of action of antidepressant drugs. Previous in vivo imaging studies have studied striatal dopamine D2 receptor availability in depression but the results are equivocal thus far.

Objective

To study the striatal and thalamic dopamine D2 receptor availability in drug-naive patients with major depression was the aim of this study.

Materials and methods

Caudate, putamen, and thalamic dopamine D2 receptor availability was estimated using positron emission tomography and [11C]raclopride in 25 treatment-seeking drug-free patients (of whom 24 were drug-naive) with major depression (primary care patients) as well as in 19 demographically similar healthy control subjects. Receptor availability was expressed as the binding potential (BPND), and analyses were carried out based on both regional and voxel-level BPND estimates.

Results

No statistically significant differences in [11C]raclopride BPND were observed between the groups either in the caudate nucleus (+1.7%, CI −4.8% to +8.3%), putamen (−1.0%, CI −7.2% to 5.1%), thalamus (−2.4%, CI −8.7% to 4.0%), or ventral striatum (−3.8%, CI −9.3% to +1.6%). In the patients, depressive symptoms were not associated with [11C]raclopride BPND in any region.

Conclusions

The findings in this sample of treatment-seeking, drug-naive and predominantly first-episode patients with major depression do not support the involvement of striatal dopamine D2 receptors in the pathophysiology of the illness, but do not exclude the potential importance of dopaminergic mechanisms in antidepressant drug action.

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Acknowledgments

This study was financially supported by Signe and Ane Gyllenberg Foundation, The Social Insurance Institution of Finland, and the Turku University Central Hospital (grant P3848). The staffs of Turku PET Centre and the MRI Unit of Turku University Central Hospital are acknowledged for skillful assistance in performing PET and MRI scanning.

Financial disclosures

Dr. Hirvonen has received lecture fees from AstraZeneca, Bristol-Myers Squibb, Janssen-Cilag, Lundbeck, and Novartis, congress travel grants from AstraZeneca and Lundbeck, and research funding from Orion Pharma and Lundbeck. Dr. Karlsson has received lecture fees from AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, and Wyeth. Dr. Markkula has received lecture fees from Eli Lilly, GlaxoSmithKline, and Janssen-Cilag. Dr. Hietala has received lecture fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, and Lundbeck, congress travel grants from AstraZeneca, Bristol-Myers Squibb, and Eli Lilly, and has acted as a consultant for Orion Pharma. Drs. Kajander, Rasi-Hakala, Någren, and Salminen report no biomedical financial interests or potential conflicts of interest.

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Authors and Affiliations

  1. Department of Psychiatry, University of Turku, Turku, Finland

    Jussi Hirvonen, Hasse Karlsson, Jaana Kajander, Juha Markkula, Helena Rasi-Hakala & Jarmo Hietala

  2. Turku PET Centre, University of Turku and Turku University Central Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland

    Jussi Hirvonen, Kjell Någren & Jarmo Hietala

  3. Department of Psychiatry, University of Helsinki, Turku, Finland

    Hasse Karlsson

  4. The Social Insurance Institution of Finland, Turku, Finland

    Jouko K. Salminen

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  1. Jussi Hirvonen
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Correspondence to Jussi Hirvonen.

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Hirvonen, J., Karlsson, H., Kajander, J. et al. Striatal dopamine D2 receptors in medication-naive patients with major depressive disorder as assessed with [11C]raclopride PET. Psychopharmacology 197, 581–590 (2008). https://doi.org/10.1007/s00213-008-1088-9

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  • DOI: https://doi.org/10.1007/s00213-008-1088-9

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