Autoradiographic distribution of serotonin transporters and receptor subtypes in human brain

108

The present study examined the effects of acute tryptophan (Trp) depletion (ATD), a well-recognized method to lower central serotonin (5-HT) metabolism, on brain activation during a facial emotion perception task. Brain activation was measured using fMRI, and healthy female volunteers with a positive family history of unipolar depression (FH + ) were compared to healthy female volunteers without such a history (FHÀ). Participants viewed two morphed faces and were instructed to choose between the faces based either on the intensity of the emotional expression (direct task) or the gender of the face (incidental task). In the FH + group, depletion led to the expected lowering of mood, which partly determined the effect of depletion on performance and brain activation. A stronger mood lowering effect was associated with less accurate performance on faces expressing a negative emotion in the incidental task and a stronger right amygdala response to fearful faces in comparison to happy faces. These results were explained in terms of a mood-induced bias leading to a stronger impact of the expressed negative emotion which subsequently leads to more interference in the incidental task and a stronger amygdala response. It was concluded that the effects of ATD on mood, performance, and brain activation in a facial emotion perception task depend on family history of depression. Performance and brain activation partly depend on the effect of ATD on mood.

Section: Discussionsupporting

confidence: 86%

Effects of Acute Tryptophan Depletion on Mood and Facial Emotion Perception Related Brain Activation and Performance in Healthy Women with and without a Family History of Depression

Veen

Evers

Deutz

et al. 2006

108

“…Immunohistochemical studies reveal the presence of serotonin-1A (Aznar et al, 2003) and serotonin-2A (Jakab and Goldman-Rakic, 2000;Pazos et al, 1987b) receptors on nearly all CB-IR and PV-IR neurons. Moreover, serotonin-1A receptors are preferentially found in layer II of human prefrontal cortex (Burnet et al, 1995;Pazos et al, 1987a;Varnas et al, 2004) and PET studies show a significant reduction in radioligand binding to serotonin-1A receptors in depressed subjects (Bhagwagar et al, 2004a;Sargent et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

GABAergic Neurons Immunoreactive for Calcium Binding Proteins are Reduced in the Prefrontal Cortex in Major Depression

Rajkowska

O'Dwyer

Teleki

et al. 2006

372

234

Post-mortem morphometric studies report reductions in the average density and size of cortical neurons in the dorsolateral prefrontal cortex (dlPFC) and orbitofrontal cortex (ORB) in major depressive disorder (MDD). The contribution of specific neuronal phenotypes to this general pathology in depression is still unclear. Post-mortem sections from the dlPFC and ORB regions of 14 subjects with MDD and 11 controls were immunostained to visualize calbindin-immunoreactive (CB-IR) and parvalbumin-immunoreactive (PV-IR) presumptive GABAergic neurons. A three-dimensional cell counting probe was used to assess the cell packing density and size of CB-IR neurons in layers II + IIIa and PV-IR neurons in layers III-VI. The density of CB-IR neurons was significantly reduced by 50% in depression in the dlPFC and there was a trend toward reduction in the ORB. The size of CB-IR somata was significantly decreased (18%) in depression in the dlPFC with a trend toward reduction in the ORB. In contrast, there was no difference in the density of PV-IR neurons between the depressed and control groups in the dlPFC. The size of PV-IR neuronal soma was unchanged in depressed compared to control subjects in either dlPFC or ORB. In depression, subpopulations of GABAergic neurons may be affected differently in dlPFC and ORB. A significant reduction in the density and size of GABAergic interneurons immunoreactive for calcium binding proteins was found predominantly in the dlPFC region. These cellular changes are consistent with recent neuroimaging studies revealing a reduction in the cortical levels of GABA in depression.

“…Most of the areas in which tryptophan depletion increased neural responses to emotional relative to neutral stimuli receive moderate-to-high densities of serotonergic projections from the dorsal and/or median raphe nuclei (Jacobs and Azmitia, 1992;Varnas et al, 2004). Multiple 5-HT receptor subtypes are present in each region, some of which when stimulated exert hyperpolarizing (ie inhibitory) effects on the neurons where they are expressed, and some of which exert depolarizing (ie excitatory) effects (Andrade, 1998;Peroutka et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Acute Tryptophan Depletion on the Neural Correlates of Emotional Processing in Healthy Volunteers

Roiser

Lévy

Fromm

et al. 2007

The processing of affective material is known to be modulated by serotonin (5-HT), but few studies have used neurophysiological measures to characterize the effect of changes in 5-HT on neural responses to emotional stimuli. We used functional magnetic resonance imaging to investigate the effect of acute tryptophan depletion, which reduces central 5-HT synthesis, on neural responses to emotionally valenced verbal stimuli. Though no participants experienced significant mood change, emotional information processing was substantially modified following 5-HT depletion. A behavioral bias toward positive stimuli was attenuated following depletion, which was accompanied by increased hemodynamic responses during the processing of emotional words in several subcortical structures. Inter-individual differences in tryptophan depletion-elicited anxiety correlated positively with the caudate bias toward negative stimuli. These data suggest that 5-HT may play an important role in mediating automatic negative attentional biases in major depression, as well as resilience against negative distracting stimuli in never-depressed individuals.