Elsevier

Behavioural Brain Research

Volume 329, 30 June 2017, Pages 180-185
Behavioural Brain Research

Research report
The interaction of corticotropin-releasing hormone receptor gene and early life stress on emotional empathy

https://doi.org/10.1016/j.bbr.2017.04.047Get rights and content

Abstract

Early life stress (ELS) is associated with increased vulnerability for depression, changes to the corticotropin-releasing hormone (CRH) system and structural and functional changes in hippocampus. Single nucleotide polymorphisms in the CRH receptor 1 (CRHR1) gene interact with ELS to predict depression, cognitive functions and hippocampal activity. Social cognition has been related to hippocampal function and might be crucial for maintaining mental health. However, the interaction of CRHR1 gene variation and ELS on social cognition has not been investigated yet. We assessed social cognition in 502 healthy subjects to test effects of ELS and the CRHR1 gene. Participants were genotyped for rs110402 and rs242924. ELS was assessed by Childhood Trauma Questionnaire, social cognition was measured via Multifaceted Empathy Test and Empathy Quotient. Severity of ELS was associated with decreased emotional, but not cognitive empathy. Subjects with the common homozygous GG GG genotype showed decreased implicit emotional empathy after ELS exposure regardless of its severity. The results reveal that specific CRHR1 polymorphisms moderate the effect of ELS on emotional empathy. Exposure to ELS in combination with a vulnerable genotype results in impaired emotional empathy in adulthood, which might represent an early marker of increased vulnerability after ELS.

Section snippets

Background

Early life stress (ELS) such as emotional or physical neglect and abuse considerably increase the risk of developing psychiatric disorders in later life [1]. Converging evidence from animal models and human studies indicates that ELS not only causes persisting changes to the stress system, i.e., the corticotropin-releasing hormone (CRH) system and the hypothalamic-pituitary-adrenal (HPA) axis [2], but also induces structural, functional, and epigenetic changes in brain regions involved in

Subjects

All subjects were recruited from responses to advertising in local newspapers and mailing lists. The initial sample consisted of N = 1402. In a first step, we excluded all participants that did not meet the following inclusion criteria: age between 18 and 90 years, absence of present and past diagnosis of psychiatric or neurologic disorder, absence of major or unstable general medical conditions, and ability to participate in study procedures. Absence of present and past diagnosis of psychiatric

Sample

In the final sample of N = 541, data from 5 subjects could not be evaluated because of missing CTQ, MET or EQ data. Furthermore, we had to exclude 24 subjects with missing genetic data and 9 subjects with rare genotype combinations. One subject was identified as an outlier due to a CTQ-score of 113 and also excluded, which resulted in a corrected sample size of N = 502 (see Table 1). Participants represent the middle range of socioeconomic status in the general population of Germany and more than

Conclusions

The present study investigated the effects of CRHR1 gene on the relationship between ELS experience and social cognition in healthy adults. Subjects were genotyped for rs110402 and rs242924 within the CRHR1 gene. We found that severity of ELS was associated with decreased implicit and explicit emotional, but not cognitive empathy. Exposure to ELS had a particularly strong impact on implicit emotional empathy in subjects with the common homozygous GG GG genotype. In this group, subjects showed

Conflict of interest

None.

Financial support

This research received no specific grant from any funding agency, commercial or not-for-profit sectors.

Acknowledgement

None.

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      The rs242924 polymorphism had been associated with higher cortisol levels in a social stress challenge compared to A allele carriers (Mahon et al., 2013a). Moreover, the combination of CRHR1 rs242924 GG and rs110402 GG genotypes has been linked with decreased implicit emotional empathy in individuals exposed to early life stress (Grimm et al., 2017). Considering the evidence supporting a role of the abovementioned genetic variations in the domain of cooperative and empathic behavior, we expected significant associations with trait empathy.

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      Different groups have suggested an effect of CRHR1 SNPs rs110402 and rs242924 in the association between early life stress and age on hippocampal and prefrontal cortex tasks such as working memory (Fuge et al., 2014; Grimm et al., 2015). The same variation has also been associated with impaired emotional empathy related to early life stress (Grimm et al., 2017). Some studies focusing on the TAT haplotype of CRHR1 (formed by rs7209436, rs110402, and rs242924) have shown an association with an increase in brooding rumination, a recognized cognitive endophenotype of depression, in children with depressed mothers (Van Hulle et al., 2017; Woody et al., 2016).

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