Sexually dimorphic responses to early adversity: implications for affective problems and autism spectrum disorder
Open accessAbstract
During gestation, development proceeds at a pace that is unmatched by any other stage of the life cycle. For these reasons the human fetus is particularly susceptible not only to organizing influences, but also to pathogenic disorganizing influences. Growing evidence suggests that exposure to prenatal adversity leads to neurological changes that underlie lifetime risks for mental illness. Beginning early in gestation, males and females show differential developmental trajectories and responses to stress. It is likely that sex-dependent organization of neural circuits during the fetal period influences differential vulnerability to mental health problems. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two developmental disorders: affective problems (greater female prevalence) and autism spectrum disorder (greater male prevalence). Recent prospective studies illustrating the neurodevelopmental consequences of fetal exposure to stress and stress hormones for males and females are considered here. Plausible biological mechanisms including the role of the sexually differentiated placenta are discussed.
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Men, for reasons not yet understood, are particularly vulnerable to in utero and early life adversity affecting brain maturation.
“In contrast, men, for reasons not yet understood, are particularly vulnerable to in utero and early life adversity affecting brain maturation (156).”
From Where Sex Meets Gender: How Sex and Gender Come Together to Cause Sex Differences in Mental Illness (2022) · cites this paper as [156]
Section III says males are more susceptible to fetal adversity and more vulnerable to extreme developmental impairments; the Background says the developing fetal brain is susceptible to environmental stress. But the Outlook cautions against a general assumption of greater male susceptibility: early adversity affects both sexes in different ways. The claim therefore overgeneralizes the paper’s account of vulnerability affecting brain development. (LLM, conf=0.84)
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References 123 · Cited by 159
Research works printed but not linked: 2
- Levine J Sex differences in neuroendocrine systems Frontiers in Neuroendocrinology 2014 in press
- Nemeroff CB Early-life adversity, CRF dysregulation, and vulnerability to mood and anxiety disorders Psychopharmacol Bull 2004 38 14 20 15278013
- Authors
- Davis, E. P., & Pfaff, D.
- Affiliations
- University of Denver (US)
- Rockefeller University (US)
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 49
- Pages
- 11-25
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC4165713
- OpenAlex
- W2120518123
- Cited by
- 159
- References
- 123
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 16 · 2023: 11 · 2022: 13 · 2021: 22 · 2020: 19 · 2019: 13 · 2018: 15 · 2017: 11 · 2016: 13 · 2015: 14 · 2013: 1
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons - DU (University of Denver) (submittedVersion)
- Funders
- NIH (R01 HD065823, R01 HD005751)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- prenatal adversity, early life stress, autism spectrum disorder, mood disorders, sex differences, fetal brain development, stress hormones, placenta
- MeSH terms
- Animals, Brain, Child Development Disorders, Pervasive, Female, Humans, Hypothalamo-Hypophyseal System, Models, Biological, Pituitary-Adrenal System, Placentation, Pregnancy, Risk Factors, Sex Characteristics, Stress, Psychological, Mood Disorders, Fetal Development
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