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The Moderating Effects of Sex on Consequences of Childhood Maltreatment: From Clinical Studies to Animal Models


The Moderating Effects of Sex on Consequences of Childhood Maltreatment: From Clinical Studies to Animal Models

Jordon D White et al. Front Neurosci.


Stress has pronounced effects on the brain, and thus behavioral outputs. This is particularly true when the stress occurs during vulnerable points in development. A review of the clinical literature regarding the moderating effects of sex on psychopathology in individuals exposed to childhood maltreatment (CM) is complicated by a host of variables that are difficult to quantify and control in clinical settings. As a result, the precise role of sex in moderating the consequences of CM remains elusive. In this review, we explore the rationale for studying this important question and their implications for treatment. We examine this issue using the threat/deprivation conceptual framework and highlight a growing body of work demonstrating important sex differences in human studies and in animal models of early life stress (ELS). The challenges and obstacles for effectively studying this question are reviewed and are followed by recommendations on how to move forward at the clinical and preclinical settings. We hope that this review will help inspire additional studies on this important topic.

Keywords: animal models; childhood maltreatment; deprivation; early life stress; limited bedding nesting; maternal separation; sex; threat.


The threat/deprivation conceptualization is shown for human subtypes of CM (A) and rodent models of ELS (B).

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    1. Aarts E., Verhage M., Veenvliet J. V., Dolan C. V., Van Der Sluis S. (2014). A solution to dependency: using multilevel analysis to accommodate nested data. Nat. Neurosci. 17 491–496. 10.1038/nn.3648 - DOI - PubMed
    1. Altemus M. (2006). Sex differences in depression and anxiety disorders: potential biological determinants. Horm. Behav. 50 534–538. 10.1016/j.yhbeh.2006.06.031 - DOI - PubMed
    1. Anda R. F., Felitti V. J., Bremner J. D., Walker J. D., Whitfield C., Perry B. D., et al. (2006). The enduring effects of abuse and related adverse experiences in childhood. A convergence of evidence from neurobiology and epidemiology. Eur. Arch. Psychiatry Clin. Neurosci. 256 174–186. 10.1007/s00406-005-0624-4 - DOI - PMC - PubMed
    1. Anier K., Malinovskaja K., Pruus K., Aonurm-Helm A., Zharkovsky A., Kalda A. (2014). Maternal separation is associated with DNA methylation and behavioural changes in adult rats. Eur. Neuropsychopharmacol. 24 459–468. 10.1016/j.euroneuro.2013.07.012 - DOI - PubMed
    1. Anisman H., Zaharia M. D., Meaney M. J., Merali Z. (1998). Do early-life events permanently alter behavioral and hormonal responses to stressors? Int. J. Dev. Neurosci. 16 149–164. 10.1016/s0736-5748(98)00025-2 - DOI - PubMed

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