Early life stress causes sex-specific changes in adult fronto-limbic connectivity that differentially drive learning

Author:

White Jordon D1,Arefin Tanzil M2,Pugliese Alexa1,Lee Choong H2,Gassen Jeff3,Zhang Jiangyang2,Kaffman Arie1ORCID

Affiliation:

1. Department of Psychiatry, Yale University School of Medicine, New Haven, United States

2. Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, United States

3. Department of Psychology, Texas Christian University, Fort Worth, United States

Abstract

It is currently unclear whether early life stress (ELS) affects males and females differently. However, a growing body of work has shown that sex moderates responses to stress and injury, with important insights into sex-specific mechanisms provided by work in rodents. Unfortunately, most of the ELS studies in rodents were conducted only in males, a bias that is particularly notable in translational work that has used human imaging. Here we examine the effects of unpredictable postnatal stress (UPS), a mouse model of complex ELS, using high resolution diffusion magnetic resonance imaging. We show that UPS induces several neuroanatomical alterations that were seen in both sexes and resemble those reported in humans. In contrast, exposure to UPS induced fronto-limbic hyper-connectivity in males, but either no change or hypoconnectivity in females. Moderated-mediation analysis found that these sex-specific changes are likely to alter contextual freezing behavior in males but not in females.

Funder

National Institute of Mental Health

National Center for Advancing Translational Sciences

National Institute of Neurological Disorders and Stroke

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference113 articles.

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