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Gene–environment interactions between HPA-axis genes and childhood maltreatment in depression: a systematic review

Published online by Cambridge University Press:  06 January 2020

Caroline Normann Open the ORCID record for Caroline Normann [Opens in a new window]  and
Henriette N. Buttenschøn
Caroline Normann*
Affiliation:
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Henriette N. Buttenschøn
Affiliation:
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark NIDO Denmark, Research and Education in Health, Regional Hospital West Jutland, Herning, Denmark
*
Author for correspondence: Caroline Normann, Email: carolinensoe@gmail.com
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Abstract

Objective:

Gene–environment (GxE) interactions may comprise an important part of the aetiology of depression, and childhood maltreatment (CM), a significant stressor, has consistently been linked to depression. Hence, in this systematic review, we aimed to investigate the interaction between hypothalamus–pituitary–adrenal axis (HPA-axis) genes and CM in depression.

Methods:

We conducted a literature search using the Pubmed, Embase, and PsychINFO databases in adherence with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We included studies investigating GxE interactions between HPA-axis genes [Angiotensin Converting Enzyme (ACE), Arginine Vasopressin (AVP), Corticotrophin Releasing Hormone (CRH), Corticotrophin Releasing Hormone Receptor 1 (CRHR1), Corticotrophin Releasing Hormone Receptor 2 (CRHR2), FK506 binding protein (FKBP5), Nuclear Receptor subfamily 3 group C member 1 (NR3C1), Nuclear Receptor subfamily 3 group C member 2 (NR3C2)] and CM in depression.

Results:

The literature search identified 159 potentially relevant studies. Following screening, 138 of these were excluded. Thus, 21 studies, investigating a total of 51 single nucleotide polymorphisms, were included in the final study. The most prevalent genes in the current study were CRHR1 and FKBP5. Significant GxE interactions were reported in seven of eight studies for CRHR1:rs110402 and CM, and in five of eight studies for FKBP5:rs1360780 and CM. In summary, our results suggest possible GxE interactions between CRHR1, FKBP5, NR3C1, and NR3C2 and CM, respectively. For the remaining genes, no relevant literature emerged.

Conclusions:

We find that genetic variation in four HPA-axis genes may influence the effects of CM in depression.

Keywords

depressiongene–environment interactionsadult survivors of child adverse eventssingle nucleotide polymorphismlife change events
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 32 , Issue 3 , June 2020 , pp. 111 - 121
Copyright
© Scandinavian College of Neuropsychopharmacology 2020

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