A High-Resolution<i>In Vivo</i>Atlas of the Human Brain's Serotonin System

Beliveau, Vincent; Ganz, Melanie; Feng, Li; Ozenne, Brice; Højgaard, Liselotte; Fisher, Patrick M.; Svarer, Claus; Greve, Douglas N.; Knudsen, Gitte Moos

doi:10.1523/jneurosci.2830-16.2016

Cited by 297 publications

(248 citation statements)

References 51 publications

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“…The ubiquity of 5-hydroxytryptamine, 5-HT (i.e., serotonin), receptors in the human brain has been established, and their varying distributions were quantified by high-resolution neuroimaging data consisting of positron emission tomography (PET) and magnetic resonance (MR) imaging scans (Beliveau et al, 2016). However, animal experiments in cats show that the majority of brain 5-HT receptor neurons lie in the brainstem raphe nuclei, of which the anterior two nuclei supply most of the 5-HT to the forebrain, while the posterior nuclei supply the pyramidal neurons in the spinal cord (Jacobs & Fornal, 1997).…”

Section: Introductionmentioning

confidence: 99%

The effect of a single dose of escitalopram on sensorimotor networks

et al. 2018

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IntroductionServing as a pilot study of poststroke pharmacotherapy, the present investigation was intended to establish the effect of a single dose of escitalopram on motor task performance in normal volunteers.MethodsTen healthy volunteers of median age 63 years including four females performed a well‐studied tactile manipulation task in two fMRI sessions using a double‐blind cross‐over design. The sessions began approximately three hours after ingestion of 20 mg escitalopram or placebo presented in pseudorandom order. The fMRI image sequences were submitted to principal component analysis (PCA).ResultsBased on volume correlations of task‐related principal components with the mean component images derived in our previous study, we established the reproducibility of two networks of sensorimotor activity proposed there. The network reflecting motor control (cerebral pattern I) appeared invariably in placebo and verum conditions. In contrast, the other network, attributed to diminished motor control due to distracting mental processing (cerebral pattern II), emerged less regularly and exhibited more variability. Second‐level PCAs of both conditions confirmed the findings of the initial analysis. Specifically, it validated the dominant and invariable expression of cerebral pattern I after application of a single dose of escitalopram. Dynamic causal modeling confirmed enhanced motor output as a result of a significantly increased connectivity between primary motor cortex and dorsal premotor cortex.ConclusionThis pilot study suggests the promise of stimulation by a specific serotonin reuptake inhibitor in regard to recovery and preservation of motor control after stroke.

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Section: Introductionmentioning

confidence: 99%

The effect of a single dose of escitalopram on sensorimotor networks

et al. 2018

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“…It is important to note as not all mRNA levels provide consistent protein levels. Of note, elegant investigations recently demonstrated strong correlations between mRNA and protein expression within the cerebral cortex for a number of 5-HT receptors, including 5-HT 1A receptor and 5-HT 2A receptor [40]. Secondly, we may have missed a behavioral phenotype in our model.…”

Section: Discussionmentioning

confidence: 97%

Perinatal SSRI exposure permanently alters cerebral serotonin receptor mRNA in mice but does not impact adult behaviors

Meyer

Dexter

et al. 2017

The Journal of Maternal-Fetal & Neonatal Medicine

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Purpose: Associations have been made between maternal selective serotonin reuptake inhibitor (SSRI) use during pregnancy and altered behavior in offspring, including an increased risk of autism. Given the important role serotonin plays in behavior, we hypothesized SSRI exposure in the perinatal period would alter central serotonin receptor expression and program adult behaviors in mice. Methods: Female mice were injected with sertraline or saline throughout pregnancy. Offspring continued to receive injections on postnatal days 1–14, a time period in mice similar to the third trimester in human pregnancy. Adult offspring underwent behavioral testing and serotonin receptor mRNA levels were quantified. Results: Compared to controls, SSRI exposed mice did not have a reduction in social interactions, spatial learning, or exploratory behavior. As adults, sertraline exposed mice had significantly increased mRNA levels of multiple 5-HT receptors, serotonin transporter (5-HTT), and tryptophan hydroxylase isoform 2 in the cerebral cortex. Conclusion: Although no behavioral phenotype was observed, SSRI exposure in the perinatal period permanently alters cerebral receptor mRNA levels. We speculate these shifts in mRNA expression provide important compensation during SSRI exposure. Further pre-clinical and clinical investigation into additional serotonin-regulated phenotypes is necessary to further assess the long-term implications of perinatal SSRI exposure.

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“…Of the 11 5D-ASC constructs, the four constructs with high emotionality are: Feeling of Unity, Bliss, Spiritual Experience, and Insightfulness. Psilocybin modulates activity and functional connectivity throughout the limbic system, which is considered the central emotional network [13,16,17,36,37]. Because the subjective effects of psilocybin are primarily mediated by the 5-HT2Ar [18], we chose regions of the limbic system with the highest 5-HT2Ar protein expression, and identified the cingulate cortex based on prior research ( Figure 1A) [38].…”

Section: Introductionmentioning

confidence: 99%

Rostral Anterior Cingulate Thickness Predicts the Emotional Psilocybin Experience

Lewis

Preller²,

Braden

et al. 2020

Biomedicines

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Psilocybin is the psychoactive compound of mushrooms in the psilocybe species. Psilocybin directly affects a number of serotonin receptors, with highest affinity for the serotonin 2A receptor (5HT-2Ar). Generally, the effects of psilocybin, and its active metabolite psilocin, are well established and include a range of cognitive, emotional, and perceptual perturbations. Despite the generality of these effects, there is a high degree of inter-individual variability in subjective psilocybin experiences that are not well understood. Others have shown brain morphology metrics derived from magnetic resonance imaging (MRI) can predict individual drug response. Due to high expression of serotonin 2A receptors (5HT-2Ar) in the cingulate cortex, and its prior associations with psilocybin, we investigate if cortical thickness of this structure predicts the psilocybin experience in healthy adults. We hypothesized that greater cingulate thickness would predict higher subjective ratings in sub-scales of the Five-Dimensional Altered State of Consciousness (5D-ASC) with high emotionality in healthy participants (n = 55) who received oral psilocybin (either low dose: 0.160 mg/kg or high dose: 0.215 mg/kg). After controlling for sex, age, and using false discovery rate (FDR) correction, we found the rostral anterior cingulate predicted all four emotional sub-scales, whereas the caudal and posterior cingulate did not. How classic psychedelic compounds induce such large inter-individual variability in subjective states has been a long-standing question in serotonergic research. These results extend the traditional set and setting hypothesis of the psychedelic experience to include brain structure metrics.

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A High-ResolutionIn VivoAtlas of the Human Brain's Serotonin System

Cited by 297 publications

References 51 publications

The effect of a single dose of escitalopram on sensorimotor networks

The effect of a single dose of escitalopram on sensorimotor networks

Perinatal SSRI exposure permanently alters cerebral serotonin receptor mRNA in mice but does not impact adult behaviors

Rostral Anterior Cingulate Thickness Predicts the Emotional Psilocybin Experience

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