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Psychoneuroendocrinology. 2014 Nov;49:11-25. doi: 10.1016/j.psyneuen.2014.06.014. Epub 2014 Jun 26.

Sexually dimorphic responses to early adversity: implications for affective problems and autism spectrum disorder.

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Neurodevelopmental Research Program, Department of Psychology, University of Denver, Denver, CO, USA; Department of Psychiatry and Human Behavior, University of California Irvine, Orange, CA 92868, USA. Electronic address:
Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY 10021, USA.


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.


Anxiety; Autism; Depression; Early adversity; Epigenetic; Fetal programming; Placenta; Prenatal; Sex differences; Stress

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