Influence of maternal depression on children's brooding rumination: Moderation by CRHR1 TAT haplotype

Abstract

There is growing evidence that brooding rumination plays a key role in the intergenerational transmission of major depressive disorder (MDD) and may be an endophenotype for depression risk. However, less is known about the mechanisms underlying this role. Therefore, the goal of the current study was to examine levels of brooding in children of mothers with a history of MDD (n = 129) compared to children of never depressed mothers (n = 126) and to determine whether the variation in a gene known to influence hypothalamic-pituitary-adrenal axis functioning—corticotropin-releasing hormone receptor 1 (CRHR1) —would moderate the link between maternal MDD and children's levels of brooding. We predicted children of mothers with a history of MDD would exhibit higher levels of brooding than children of mothers with no lifetime depression history but that this link would be stronger among children carrying no copies of the protective CRHR1 TAT haplotype. Our results supported these hypotheses and suggest that the development of brooding among children of depressed mothers, particularly children without the protective CRHR1 haplotype, may serve as an important mechanism of risk for the intergenerational transmission of depression.

Keywords:

• Intergenerational transmission of depression
• Brooding rumination
• CRHR1
• Endophenotype
• Major depressive disorder
• Cognitive vulnerability

Acknowledgements

We would like to thank Ashley Johnson, Lindsey Stone, Andrea Hanley, Katie Burkhouse, Sydney Meadows, Michael Van Wie and Devra Alper for their help in conducting assessments for this project, and Kayla Beaucage for her help with genotyping.

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes

¹ We reran our analyses using listwise deletion to account for the presence of missing data, leaving us with a sample size of 244 parent–child dyads for our analyses. The mother MDD × CRHR1 interaction and the main effect of mother MDD among children with no copies of the TAT haplotype remained significant. In addition, all tests of robustness were maintained. The only difference between the original data and the estimated data was for the main effect of mother MDD across the sample, which was significant in the estimated data (p = .05) and marginally significant in the original data (p = .08).

² Analyses of individual SNPs (rs7209436, rs110402 and rs242924) were identical to those reported for the overall haplotype. Specifically, for each SNP, we found a significant mother MDD × CRHR1 SNP interaction (all ps < .04). In addition, we found significant main effects of mother MDD on children’s levels of brooding rumination among children with no copies of the rs7209436 T allele, rs110402 A allele and rs242924 T allele (all ps < .02).

Additional information

Funding

This project was supported by grants from the National Institute of Child Health and Human Development [grant number HD057066] and National Institute of Mental Health [grant number MH098060] awarded to B. E. Gibb and grant number 1S10RR023457-01A1 and Shared equipment grants (ShEEP) from the Medical Research Service of the Department of Veteran Affairs awarded to J. E. McGeary. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the NIH.