Relationships Between Serotonin Availability and Frontolimbic Response to Fearful and Threatening Faces

Overview

Journal Sci Rep

Specialty Science

Date 2023 Jan 27

PMID 36707612

Authors

R Janet

N Costes

I Merida

E Derrington

J C Dreher

Affiliations

Soon will be listed here.

Abstract

Serotonin is a critical neurotransmitter in the regulation of emotional behavior. Although emotion processing is known to engage a corticolimbic circuit, including the amygdala and prefrontal cortex, exactly how this brain system is modulated by serotonin remains unclear. Here, we hypothesized that serotonin modulates variability in excitability and functional connectivity within this circuit. We tested whether this modulation contributes to inter-individual differences in emotion processing. Using a multimodal neuroimaging approach with a simultaneous PET-3T fMRI scanner, we simultaneously acquired BOLD signal while participants viewed emotional faces depicting fear and anger, while also measuring serotonin transporter (SERT) levels, regulating serotonin functions. Individuals with higher activity of the medial amygdala BOLD in response to fearful or angry facial expressions, who were temperamentally more anxious, also exhibited lower SERT availability in the dorsal raphe nucleus (DRN). Moreover, higher connectivity of the medial amygdala with the left dorsolateral prefrontal and the anterior cingulate cortex was associated with lower levels of SERT availability in the DRN. These results demonstrate the association between the serotonin transporter level and emotion processing through changes in functional interactions between the amygdala and the prefrontal areas in healthy humans.

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References

Baas D, Aleman A, Kahn R . Lateralization of amygdala activation: a systematic review of functional neuroimaging studies. Brain Res Brain Res Rev. 2004; 45(2):96-103. DOI: 10.1016/j.brainresrev.2004.02.004. View

Neubert F, Mars R, Sallet J, Rushworth M . Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex. Proc Natl Acad Sci U S A. 2015; 112(20):E2695-704. PMC: 4443352. DOI: 10.1073/pnas.1410767112. View

LeDoux J . The emotional brain, fear, and the amygdala. Cell Mol Neurobiol. 2003; 23(4-5):727-38. PMC: 11530156. DOI: 10.1023/a:1025048802629. View

Davis M, Whalen P . The amygdala: vigilance and emotion. Mol Psychiatry. 2001; 6(1):13-34. DOI: 10.1038/sj.mp.4000812. View

Hariri A, Mattay V, Tessitore A, Kolachana B, Fera F, Goldman D . Serotonin transporter genetic variation and the response of the human amygdala. Science. 2002; 297(5580):400-3. DOI: 10.1126/science.1071829. View

Glascher J, Adolphs R . Processing of the arousal of subliminal and supraliminal emotional stimuli by the human amygdala. J Neurosci. 2003; 23(32):10274-82. PMC: 6741000. View

Demenescu L, Kortekaas R, Cremers H, Renken R, van Tol M, van der Wee N . Amygdala activation and its functional connectivity during perception of emotional faces in social phobia and panic disorder. J Psychiatr Res. 2013; 47(8):1024-31. DOI: 10.1016/j.jpsychires.2013.03.020. View

Ruhe H, Ooteman W, Booij J, Michel M, Moeton M, Baas F . Serotonin transporter gene promoter polymorphisms modify the association between paroxetine serotonin transporter occupancy and clinical response in major depressive disorder. Pharmacogenet Genomics. 2008; 19(1):67-76. DOI: 10.1097/FPC.0b013e32831a6a3a. View

Schiller D, Delgado M . Overlapping neural systems mediating extinction, reversal and regulation of fear. Trends Cogn Sci. 2010; 14(6):268-76. PMC: 3848321. DOI: 10.1016/j.tics.2010.04.002. View

10.

Stein M, Simmons A, Feinstein J, Paulus M . Increased amygdala and insula activation during emotion processing in anxiety-prone subjects. Am J Psychiatry. 2007; 164(2):318-27. DOI: 10.1176/ajp.2007.164.2.318. View

11.

Hammers A, Allom R, Koepp M, Free S, Myers R, Lemieux L . Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Hum Brain Mapp. 2003; 19(4):224-47. PMC: 6871794. DOI: 10.1002/hbm.10123. View

12.

Iscan Z, Rakesh G, Rossano S, Yang J, Zhang M, Miller J . A positron emission tomography study of the serotonergic system in relation to anxiety in depression. Eur Neuropsychopharmacol. 2017; 27(10):1011-1021. PMC: 5623123. DOI: 10.1016/j.euroneuro.2017.07.009. View

13.

Lesch K, Bengel D, Heils A, Sabol S, Greenberg B, Petri S . Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science. 1996; 274(5292):1527-31. DOI: 10.1126/science.274.5292.1527. View

14.

Frank D, Dewitt M, Hudgens-Haney M, Schaeffer D, Ball B, Schwarz N . Emotion regulation: quantitative meta-analysis of functional activation and deactivation. Neurosci Biobehav Rev. 2014; 45:202-11. DOI: 10.1016/j.neubiorev.2014.06.010. View

15.

Porcelli S, Fabbri C, Serretti A . Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy. Eur Neuropsychopharmacol. 2011; 22(4):239-58. DOI: 10.1016/j.euroneuro.2011.10.003. View

16.

Kobiella A, Reimold M, Ulshofer D, Ikonomidou V, Vollmert C, Vollstadt-Klein S . How the serotonin transporter 5-HTTLPR polymorphism influences amygdala function: the roles of in vivo serotonin transporter expression and amygdala structure. Transl Psychiatry. 2012; 1:e37. PMC: 3309509. DOI: 10.1038/tp.2011.29. View

17.

Ruhe H, Koster M, Booij J, Van Herk M, Veltman D, Schene A . Occupancy of serotonin transporters in the amygdala by paroxetine in association with attenuation of left amygdala activation by negative faces in major depressive disorder. Psychiatry Res. 2014; 221(2):155-61. DOI: 10.1016/j.pscychresns.2013.12.003. View

18.

Grady C, Siebner H, Hornboll B, Macoveanu J, Paulson O, Knudsen G . Acute pharmacologically induced shifts in serotonin availability abolish emotion-selective responses to negative face emotions in distinct brain networks. Eur Neuropsychopharmacol. 2012; 23(5):368-78. DOI: 10.1016/j.euroneuro.2012.06.003. View

19.

Hariri A, Bookheimer S, Mazziotta J . Modulating emotional responses: effects of a neocortical network on the limbic system. Neuroreport. 2000; 11(1):43-8. DOI: 10.1097/00001756-200001170-00009. View

20.

Raab K, Kirsch P, Mier D . Understanding the impact of 5-HTTLPR, antidepressants, and acute tryptophan depletion on brain activation during facial emotion processing: A review of the imaging literature. Neurosci Biobehav Rev. 2016; 71:176-197. DOI: 10.1016/j.neubiorev.2016.08.031. View