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Serotonin and early life stress interact to shape brain architecture and anxious avoidant behavior – a TPH2 imaging genetics approach

Published online by Cambridge University Press:  28 September 2020

Congcong Liu ,
Lei Xu ,
Jialin Li ,
Feng Zhou ,
Xi Yang ,
Xiaoxiao Zheng ,
Meina Fu ,
Keshuang Li ,
Cornelia Sindermann  and
Christian Montag
...Show all authors
Congcong Liu
Affiliation:
The Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, 611731 Chengdu, China
Lei Xu
Affiliation:
The Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, 611731 Chengdu, China
Jialin Li
Affiliation:
The Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, 611731 Chengdu, China
Feng Zhou
Affiliation:
The Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, 611731 Chengdu, China
Xi Yang
Affiliation:
The Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, 611731 Chengdu, China
Xiaoxiao Zheng
Affiliation:
The Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, 611731 Chengdu, China
Meina Fu
Affiliation:
The Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, 611731 Chengdu, China
Keshuang Li
Affiliation:
The Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, 611731 Chengdu, China
Cornelia Sindermann
Affiliation:
Department of Molecular Psychology, Institute of Psychology and Education, Ulm University, 89081 Ulm, Germany
Christian Montag
Affiliation:
The Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, 611731 Chengdu, China Department of Molecular Psychology, Institute of Psychology and Education, Ulm University, 89081 Ulm, Germany
Yina Ma
Affiliation:
State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute of Brain Research, Beijing Normal University, 100875 Beijing, China
Dirk Scheele
Affiliation:
Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University Hospital Bonn, 53105 Bonn, Germany Department of Psychiatry, School of Medicine & Health Sciences, University of Oldenburg, 26129 Oldenburg, Germany
Richard P. Ebstein
Affiliation:
School of Management, Zhejiang University of Technology, 310023 Hangzhou, China China Center for Behavior Economics and Finance, South Western University of Finance and Economics (SWUFE), 611130, Chengdu, China
Shuxia Yao
Affiliation:
The Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, 611731 Chengdu, China
Keith M. Kendrick
Affiliation:
The Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, 611731 Chengdu, China
Benjamin Becker*
Affiliation:
The Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, 611731 Chengdu, China
*
Author for correspondence: Benjamin Becker, E-mail: ben_becker@gmx.de
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Abstract

Background

Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2) and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by anxious avoidance.

Methods

The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252).

Results

Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes.

Conclusions

The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat avoidance, thus promoting early adaptation to an adverse environment.

Keywords

Amygdalaearly life stressfrontal cortexpunishment sensitivityserotonin

Information

Type
Original Article
Information
Psychological Medicine , Volume 51 , Issue 14 , October 2021 , pp. 2476 - 2484
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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