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Sci Rep. 2018 Dec 17;8(1):17889. doi: 10.1038/s41598-018-36350-y.

Neuroticism predicts the impact of serotonin challenges on fear processing in subgenual anterior cingulate cortex.

Hornboll B1,2,3, Macoveanu J1,2, Nejad A1,4, Rowe J2,5,3, Elliott R6, Knudsen GM2,7,3, Siebner HR1,8,3, Paulson OB9,10,11,12.

Author information

1
Danish Research Centre for Magnetic Resonance (DRCMR), Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
2
Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen, Denmark.
3
University of Copenhagen, Faculty of Health Science and Medicine, Copenhagen, Denmark.
4
Child and Adolescent Mental Health Centre, Capital Region Psychiatry, Copenhagen, Denmark.
5
Department of Clinical Neurosciences, Cambridge University, Cambridge, United Kingdom.
6
Division of Neuroscience and Experimental Psychology, University of Manchester, Manchester, United Kingdom.
7
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
8
Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
9
Danish Research Centre for Magnetic Resonance (DRCMR), Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. olaf.paulson@nru.dk.
10
Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen, Denmark. olaf.paulson@nru.dk.
11
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. olaf.paulson@nru.dk.
12
University of Copenhagen, Faculty of Health Science and Medicine, Copenhagen, Denmark. olaf.paulson@nru.dk.

Abstract

The personality trait neuroticism is associated with increased vulnerability to anxiety and mood disorders, conditions linked with abnormal serotonin neurotransmission and emotional processing. The interaction between neuroticism and serotonin during emotional processing is however not understood. Here we investigate how individual neuroticism scores influence the neural response to negative emotional faces and their sensitivity to serotonergic tone. Twenty healthy participants performed an emotional face task under functional MRI on three occasions: increased serotonin tone following infusion of a selective serotonin reuptake inhibitor (SSRI), decreased serotonin tone following acute tryptophan depletion (ATD) protocol, and no serotonin challenge (control). During the task, participants performed a gender-discrimination task of neutral, fearful or angry facial expressions. Individual variations in neuroticism scores were associated with neural response of subgenual anterior cingulate cortex to fearful facial expressions. The association was however opposite under the two serotoninergic challenges. The fear-related response in this region and individual neuroticism scores correlated negatively during citalopram challenge and positively during ATD. Thus, neuroticism scores were associated with the relative impact of serotonin challenges on fear processing in subgenual anterior cingulate cortex. This finding may link to a neural mechanism for the variable therapeutic effect of SSRI treatment observed in clinical populations.

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