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

Department of Psychiatry, University of Turku, Turku, Finland.
Psychopharmacology (Impact Factor: 3.88). 06/2008; 197(4):581-90. DOI: 10.1007/s00213-008-1088-9
Source: PubMed


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.
To study the striatal and thalamic dopamine D2 receptor availability in drug-naive patients with major depression was the aim of this study.
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 (BP ND), and analyses were carried out based on both regional and voxel-level BP ND estimates.
No statistically significant differences in [11C]raclopride BP ND 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 BP ND in any region.
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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    • "This increase in D2/D3 receptor availability appears to contradict animal data in which antidepressant responses are associated with increased D2-like binding in the striatum [80]. Other studies using medication-naïve or medication-free patients have failed to find group differences in striatal receptor binding [81,82], while one additional small study reported variable changes in D2-like binding following treatment with selective serotonin reuptake inhibitors (SSRIs) with patients who showed increased binding exhibiting more clinical improvement than those who did not [83]. With respect to the D1 receptor, fewer studies have examined this system given the lack of available ligands that reliably distinguish between the D1 and serotonin 5-HT2A receptor, especially in extra-striatal areas where the receptor density of D1 and 5HT2A is roughly equivalent. "
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    Biology of Mood and Anxiety Disorders 03/2014; 4(1):5. DOI:10.1186/2045-5380-4-5
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    • "A trend towards a decrease in D2-like receptor binding was also observed in virgin females with decreased brain DHA, suggesting that the decrease in D2-like receptor binding in this brain region resulted from the change in brain DHA status, but may be augmented in the postpartum female. While this observation is consistent with the proposed hypoactivity of the mesolimbic dopamine system in depression, a postmortem study of drug-naïve patients with major depressive disorder found no differences in the density of D2 receptors in either the ventral striatum or the caudate nucleus [176]. Nevertheless, decreased densities of D2-like receptors or D2 receptor mRNA in the nucleus accumbens have been reported in several putative rat models of depression including chronic mild stress-induced anhedonia, the socially isolated Flinders sensitive line rat, and the learned helplessness model [177–179]. "
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    • "Depression is a state of reduced dopaminergic neurotransmission (Dunlop and Nemeroff, 2007); however, the relationship of DA D2 receptors to depression is unclear. Imaging studies are conflicting and some of the conflict may arise from the various techniques used (D'Haenen H and Bossuyt, 1994; Hirvonen et al., 2008). Further, regulation of extracellular DA levels may be altered in depression (Meyer et al., 2001) and could influence DA D2 receptor availability. "
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