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
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.
Available from: Diego Pizzagalli
- "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 . 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 . 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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ABSTRACT: The neuroimaging literature of Major Depressive Disorder (MDD) has grown substantially over the last several decades, facilitating great advances in the identification of specific brain regions, neurotransmitter systems and networks associated with depressive illness. Despite this progress, fundamental questions remain about the pathophysiology and etiology of MDD. More importantly, this body of work has yet to directly influence clinical practice. It has long been a goal for the fields of clinical psychology and psychiatry to have a means of making objective diagnoses of mental disorders. Frustratingly little movement has been achieved on this front, however, and the 'gold-standard' of diagnostic validity and reliability remains expert consensus. In light of this challenge, the focus of the current review is to provide a critical summary of key findings from different neuroimaging approaches in MDD research, including structural, functional and neurochemical imaging studies. Following this summary, we discuss some of the current conceptual obstacles to better understanding the pathophysiology of depression, and conclude with recommendations for future neuroimaging research.
Biology of Mood and Anxiety Disorders 03/2014; 4(1):5. DOI:10.1186/2045-5380-4-5
Available from: PubMed Central
- "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 . 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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ABSTRACT: A growing body of clinical and epidemiological evidence suggests that low dietary intake and/or tissue levels of n-3 (
-3) polyunsaturated fatty acids (PUFAs) are associated with postpartum depression. Low tissue levels of n-3 PUFAs, particularly docosahexaenoic acid (DHA), are reported in patients with either postpartum or nonpuerperal depression. Moreover, the physiological demands of pregnancy and lactation put childbearing women at particular risk of experiencing a loss of DHA from tissues including the brain, especially in individuals with inadequate dietary n-3 PUFA intake or suboptimal metabolic capabilities. Animal studies indicate that decreased brain DHA in postpartum females leads to several depression-associated neurobiological changes including decreased hippocampal brain-derived neurotrophic factor and augmented hypothalamic-pituitary-adrenal responses to stress. Taken together, these findings support a role for decreased brain n-3 PUFAs in the multifactorial etiology of depression, particularly postpartum depression. These findings, and their implications for research and clinical practice, are discussed.
Depression research and treatment 01/2011; 2011(2090-1321):467349. DOI:10.1155/2011/467349
Available from: Ronald L Cowan
- "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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ABSTRACT: Diminished dopaminergic neurotransmission contributes to decreased reward and negative eating behaviors in obesity. Bariatric surgery is the most effective therapy for obesity and rapidly reduces hunger and improves satiety through unknown mechanisms. We hypothesized that dopaminergic neurotransmission would be enhanced after Roux-en-Y-Gastric Bypass (RYGB) and Vertical Sleeve Gastrectomy (VSG) surgery and that these changes would influence eating behaviors and contribute to the positive outcomes from bariatric surgery.
Five females with obesity were studied preoperatively and at approximately 7 weeks after RYGB or VSG surgery. Subjects underwent positron emission tomography (PET) imaging with a dopamine type 2 (DA D2) receptor radioligand whose binding is sensitive to competition with endogenous dopamine. Regions of interest (ROI) relevant to eating behaviors were delineated. Fasting enteroendocrine hormones were quantified at each time point.
Body weight decreased as expected after surgery. DA D2 receptor availability decreased after surgery. Regional decreases (mean+/-SEM) were caudate 10+/-3%, putamen 9+/-4%, ventral striatum 8+/-4%, hypothalamus 9+/-3%, substantia nigra 10+/-2%, medial thalamus 8+/-2%, and amygdala 9+/-3%. These were accompanied by significant decreases in plasma insulin (62%) and leptin (41%).
The decreases in DA D2 receptor availability after RYGB and VSG most likely reflect increases in extracellular dopamine levels. Enhanced dopaminergic neurotransmission may contribute to improved eating behavior (e.g. reduced hunger and improved satiety) following these bariatric procedures.
Brain research 03/2010; 1350:123-30. DOI:10.1016/j.brainres.2010.03.064 · 2.84 Impact Factor
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