ReviewSex Differences in Vulnerability and Resilience to Stress Across the Life Span
Section snippets
Prenatal Stress Shapes an Individual’s Response to the Environment
The prenatal experience shapes an individual’s brain, body, and behavior for their lifetime and potentially even affects the response of subsequent generations through transgenerational mechanisms. Human offspring exposed to extreme gestational stress in the form of maternal starvation during the Dutch Hunger Winter had increased risk of psychiatric disorders, including affective disorders (15), addiction (16), and schizophrenia (17). Effects of famine were also associated with increased risk
Potential Mechanisms for Intergenerational Transmission of Stress: Consideration of In Utero Adaptation by Sex
Initially, female development was characterized as a passive default. However, preclinical research suggests that female brain development is an active process regulated by DNA methylation (43), an epigenetic process through which genetic transcription is silenced (44). Female fetuses have higher placental levels of DNA methyltransferase 1 (DNMT1) involved in maintenance methylation and respond to maternal variable stress with further increases, supporting the likelihood of continued recreation
Early Life Stress
Studies of children isolated in orphanages in accordance with former policies of the Romanian government have provided insight into the lasting damage of neglect and early life stress even when basic needs such as food and shelter are met. Caregiver deprivation is associated with an accentuation of the female bias toward anxiety and depressive disorders and the male bias toward impulsivity and conduct disorders 56, 57. Neuroimaging studies show abnormalities in amygdala development and
Conclusions
Male offspring are at greater risk of adverse proximal and some distal behavioral effects of gestational and early life stress owing to a lack of compensatory mechanisms and alterations in epigenetic regulation and organizational effects of hormones. The greatest distal impact of stress in male offspring at all life span epochs seems to be on cognitive ability, particularly spatial learning, and may contribute symptoms associated with autism spectrum disorder, attention-deficit/hyperactivity
Acknowledgments and Disclosures
This work was supported by the National Cancer Institute (Grant No. R01CA201295 [to CNE]), National Institute on Drug Abuse (Grant No. R01DA037289 [to CNE]), and Brain and Behavior Research Foundation (National Alliance for Research on Schizophrenia and Depression Young Investigator Grant [to GEH]).
CNE serves as a consultant for Sage Therapeutics and on the advisory board for Asarina Pharma. CNE or her spouse has personal investments in Merck & Co., Inc., Abbott Laboratories, AbbVie Inc.,
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