Elevated Putamen D ₂ Receptor Binding Potential in Major Depression With Motor Retardation: An [ ¹¹ C]Raclopride Positron Emission Tomography Study

Abstract

The results argue that extracellular dopamine is lower in subjects experiencing a major depressive episode that features motor retardation. This depression subtype should preferentially benefit from dopamine-increasing medications and should be targeted in future clinical trials of dopamine reuptake inhibitors.

Postpartum and Depression Status are Associated With Lower [11C]raclopride BPND in Reproductive-Age Women

“…Our findings of lower D 2/3 receptor BP ND in depression contrast, however, with reports of higher (D'haenen and Bossuyt, 1994;Meyer et al, 2006;Shah et al, 1997) or equivalent (Ebert et al, 1996;Parsey et al, 2001) striatal D 2/3 receptor BP ND in the whole striatum of depressed subjects relative to controls. It remains unclear how these data compare with ours; however, these studies did not discriminate the AVS from the remainder of the striatum, and the differences we identified were maximal in the ventral striatum.…”

“…In addition, the results of some of these previous studies were confounded by recent exposure to psychotropic drugs. Finally, several prior studies were in hospitalized or psychomotorically retarded depressives (Ebert et al, 1996;Meyer et al, 2006;D'haenen and Bossuyt, 1994), and several reported positive correlations between D 2/3 receptor BP ND and ratings of psychomotor slowing (Meyer et al, 2006;Shah et al, 1997). Such patients may have had lower dopaminergic tone or lower intrasynaptic DA concentrations in the dorsal striatal regions that subserve motor processing, which putatively may result in compensatory increases in D 2/3 receptor expression or affinity, or in reduced competition for binding to [ 11 C]raclopride or [ 123 I]-iodobenzamide, which are sensitive to endogenous DA levels (Laruelle, 2000).…”

“…Depressed compared to healthy individuals revealed alternatively higher (D'haenen and Bossuyt, 1994;Meyer et al, 2006;Shah et al, 1997) or equivalent (Ebert et al, 1996;Parsey et al, 2001, Schneier F, 2012, personal communication, 2012) D 2/3 receptor binding. Inconsistencies may stem from lack of discrimination between ventral and dorsal striatal D 2/3 receptor binding, failure to control for concurrent medication use and comorbid psychiatric diagnoses, lack of power to detect gender-specific differences in D 2/3 receptor binding, and lack of control for menstrual cycle phase (Wong et al, 1988).…”

“…Inconsistencies may stem from lack of discrimination between ventral and dorsal striatal D 2/3 receptor binding, failure to control for concurrent medication use and comorbid psychiatric diagnoses, lack of power to detect gender-specific differences in D 2/3 receptor binding, and lack of control for menstrual cycle phase (Wong et al, 1988). In studies of homogenous subject groups, such as psychomotorically slowed or hospitalized subjects (Ebert et al, 1996;Meyer et al, 2006;D'haenen and Bossuyt, 1994), depressed individuals had higher D 2/3 receptor binding relative to controls, and psychomotor slowing was positively correlated with D 2/3 receptor binding (Meyer et al, 2006;Shah et al, 1997) (Laruelle, 2000). Conditions of high phasic DA release, such as during the rewarding stimulus of monetary receipt, will lead to competitive binding of intrasynaptic DA to D 2/3 receptors, thus leading to reduced [ 11 C]raclopride BP ND (Zald et al, 2004).…”

Challenges for PET Neuroimaging of Depressive Disorders

“…Dopamine D 1 receptors were assessed by [ 11 C]SCH 23,390 or [ 11 C]NNC-112 in two PET studies of depression (Dougherty et al 2006;Cannon et al 2008), and both reports found less binding in striatal regions of depressed subjects than of healthy controls. Dopamine D 2/3 receptors www.intechopen.com have been assessed in five PET studies using either [ 11 C]raclopride or [ 11 C]FLB 457 in depressed subjects and healthy controls; one study noted more striatal binding by dopamine D 2/3 receptors in depressed subjects (Meyer et al 2006b), another study found less dopamine D 2/3 receptor binding in depression (Montgomery et al 2007), and three studies showed no difference between depressed and healthy subjects in dopamine D 2/3 receptor binding in brain regions (Kuroda et al 2006;Montgomery et al 2007;Busto et al 2009). The transport of dopamine as well as noradrenaline from the synaptic cleft into presynaptic terminals was assessed by PET using [ 11 C]RTI-32 in 20 Parkinson patients, some of which were depressed (Remy et al 2005).…”