Skip to main content
Log in

Harsh Parenting Predicts Novel HPA Receptor Gene Methylation and NR3C1 Methylation Predicts Cortisol Daily Slope in Middle Childhood

  • Original Research
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript


Adverse experiences in childhood are associated with altered hypothalamic–pituitary–adrenal (HPA) axis function and negative health outcomes throughout life. It is now commonly accepted that abuse and neglect can alter epigenetic regulation of HPA genes. Accumulated evidence suggests harsh parenting practices such as spanking are also strong predictors of negative health outcomes. We predicted harsh parenting at 2.5 years old would predict HPA gene DNA methylation similarly to abuse and neglect, and cortisol output at 8.5 years old. Saliva samples were collected three times a day across 3 days to estimate cortisol diurnal slopes. Methylation was quantified using the Illumina Infinium MethylationEPIC array BeadChip (850 K) with DNA collected from buccal cells. We used principal components analysis to compute a summary statistic for CpG sites across candidate genes. The first and second components were used as outcome variables in mixed linear regression analyses with harsh parenting as a predictor variable. We found harsh parenting significantly predicted methylation of several HPA axis genes, including novel gene associations with AVPRB1, CRHR1, CRHR2, and MC2R (FDR corrected p < 0.05). Further, we found NR3C1 methylation predicted a steeper diurnal cortisol slope. Our results extend the current literature by demonstrating harsh parenting may influence DNA methylation similarly to more extreme early life experiences such as abuse and neglect. Further, we show NR3C1 methylation is associated with diurnal HPA function. Elucidating the molecular consequences of harsh parenting on health can inform best parenting practices and provide potential treatment targets for common complex disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others


Download references


The authors have no acknowledgements.


This work was financially supported by Grants from R01 HD079520, R01 HD086085, and Science Foundation Arizona. The funding sources played no role in the design of the study or the collection, analysis, and interpretation of data, or the writing of the manuscript.

Author information

Authors and Affiliations



CL designed the study, performed the microarrays, analyses, and was the primary writer of the manuscript. RB collected participant data and samples. AH assisted in microarrays and data preparation. HS ran analyses and assisted in manuscript preparation. IP assisted in data analysis and manuscript preparation. MH provided genomic and methodological expertise. LD was in charge of cortisol collection, measurement, and analysis. KL was in charge of collection and maintenance of longitudinal behavioral data, and provided assistance in writing the manuscript.

Corresponding author

Correspondence to Candace R. Lewis.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare.

Ethical Approval

The Arizona State University IRB and the Western Institutional Review Board (WIRB) approved this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lewis, C.R., Breitenstein, R.S., Henderson, A. et al. Harsh Parenting Predicts Novel HPA Receptor Gene Methylation and NR3C1 Methylation Predicts Cortisol Daily Slope in Middle Childhood. Cell Mol Neurobiol 41, 783–793 (2021).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: