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

Abstract

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.

Editorial Perspective: Childhood maltreatment – the problematic unisex assumption

“…Some of the most compelling evidence comes from imaging showing that exposure to CM causes more pronounced reduction in the size of the hippocampus and the corpus callosum in males compared with females. Sex differences in prefrontal cortex activation and connectivity were also reported in the few fMRI studies that had sufficient power to examine CM‐by‐sex interaction (White & Kaffman, ). In addition, a systematic review conducted by Gershon et al () found that more than half of the 19 studies conducted in adolescents reported significant sex‐by‐CM interaction that was notable for worse clinical outcomes in males exposed to CM.…”

“…In addition, a systematic review conducted by Gershon et al () found that more than half of the 19 studies conducted in adolescents reported significant sex‐by‐CM interaction that was notable for worse clinical outcomes in males exposed to CM. Interestingly, no consistent sex‐by‐CM interaction was found in the 14 studies examining this issue in adulthood (Gershon et al, ), a finding that was replicated in three additional large meta‐analyses (White & Kaffman, ).…”

“…Although male and female brains, physiology, and immune systems share considerable similarities, there are important differences that may at least partially reflect distinct and specialized divergencies in reproductive strategies between males and females (White & Kaffman, ). In mammals, these differences are established by a surge of testosterone in males during a critical period of development (e.g.…”

“…Childhood maltreatment (CM) is a heterogeneous group of childhood adversities that can range from different forms of abuse (physical, sexual, emotional) or neglect (physical, emotional, cognitive), to severe bullying by peers. With an annual estimated cost of $500 billion in the United States alone, CM is recognized as one of the most significant risk factors for a range of psychiatric and medical conditions (White & Kaffman, ). Further, rates of numerous psychiatric, neurological, and medical conditions differ significantly between males and females (Gillies & McArthur, ), inspiring decades of research on how sex moderates consequences of CM (Gershon et al, ).…”

“…Although vulnerability to CM has been reported to vary by sex, very few findings have been consistent across studies. Moreover, most work to date has focused on how sex alters the frequencies of different psychopathologies in maltreated individuals, with little attention to whether different developmental processes may underlie these psychopathologies in males and females (White & Kaffman, ). The primary goal of this editorial was to advocate for more effective research strategies to address these questions.…”