Sex differences in the programming effects of prenatal stress on psychopathology and stress responses: An evolutionary perspective

doi:10.1016/j.physbeh.2012.02.011

Physiology & Behavior

Volume 106, Issue 5, 16 July 2012, Pages 736-740

https://doi.org/10.1016/j.physbeh.2012.02.011 Get rights and content

Abstract

There is strong evidence from animal studies that prenatal stress has different effects on male and female offspring. In general, although not always, prenatal stress increases anxiety, depression and stress responses, both hypothalamic–pituitary–adrenal and cardiovascular, in female offspring rather than in male. Males are more likely to show learning and memory deficits.

There have been few studies so far in humans which differentiate effects of prenatal stress on male and female psychopathology. Some studies support the animal models, but the evidence is inconsistent. The mediating mechanisms for any sex specific effects are little understood, but there is evidence that placental function can differ depending on the sex of the fetus.

We suggest that there may be an evolutionary reason for any sex differences in the long term effects of prenatal stress. In a stressful environment it may be adaptive for females, who are more likely to stay in one place and look after children, to be more vigilant, alert to danger and thus show more stress responsiveness. This can give rise to a more anxious or depressed phenotype. With males it may be more adaptive to go out and explore new environments, compete with other males, and be more aggressive. For this it may help to be less responsive to external stressors. More research is needed into sex differences in the effects of prenatal stress in humans, to test these ideas.

Highlights

► Prenatal stress tends to increase both anxiety and stress responses in females. ► It tends to reduce stress responses and may increase ADHD in males. ► We suggest there may be evolutionary reasons for these differences. ► Females, with children, may benefit from vigilance in a more stressful environment. ► Males may benefit from less stress responsiveness and more ability to confront danger.

Introduction

It is well known that males and females tend to differ in their pattern of psychopathology [1]. Males are more likely to be aggressive and break rules, and to suffer from attention deficit hyperactivity disorder (ADHD) [2] or autism [3]. Females are more likely to experience anxiety and depression [4]. Many of the psychiatric disorders that are more prevalent in females have an etiological association with stress and hyperarousal, and there is evidence for sex differences in the molecular responses and brain circuitry that underlie this [5]. There is also evidence that males and females differ in their cortisol response to social stress [6].

Prenatal stress has been shown to increase the likelihood of the child and later adult suffering from a range of psychopathologies, and also to alter their stress responses. It can alter the sex ratio, with more females being born than males, as has been shown for example with prenatal exposure to infectious disease [7]. In this article we will briefly review findings on the effects of prenatal stress on behaviour, learning, and on stress responses, the sex differences in these effects, and then explore possible evolutionary reasons for these differences.

Section snippets

Animal evidence for the differential effects of prenatal stress on males and females

The association between prenatal stress and offspring outcome is best shown to be causal in animal models. With rat experiments, offspring from both prenatally stressed mothers and unstressed mothers can be cross fostered to new mothers on day one after birth and postnatal effects controlled for [8]. In monkeys both prenatally stressed and control offspring can be nursery reared together [9]. Animal experiments from many different laboratories, have shown that prenatal stress can increase

The effects of prenatal stress on child outcome

Prospective studies from several different laboratories around the world have shown that if the mother is stressed, anxious or depressed while pregnant her child is more likely to have symptoms of anxiety or depression, ADHD, conduct disorder, or reduced cognitive abilities [30], [31] and increased stress reactivity [32].The evidence for these associations is very strong. In some studies the associations have been found to be particularly with prenatal anxiety rather than depression e.g. [33],

Stress reactivity

Physiological stress responses can be determined by prenatal stress and other early life predictors such as low birth weight [50]. Smaller size at birth can be an index of an adverse fetal environment, and has many causes including prenatal stress e.g. [51]. It is of interest that low birth weight has been to be shown to be associated with later altered cardiovascular responses to stress, and in most studies these changes are sex specific [52]. In general low birth weight has been found to be

Sex specific differences in placental function

The mechanisms underlying the effects of prenatal stress are not yet understood, but alterations in the function of the placenta probably contribute [55]. The placental changes may allow greater passage of cortisol [56] or other factors such as 5-HT [57], to the fetus, and these may change neurodevelopment. In animal studies, prenatal stress has been shown to cause a down regulation of the cortisol metabolising enzyme 11β-hydroxysteroid dehydrogenase type II (11β-HSD2} [58] and we have evidence

Evolutionary perspectives on fetal adaptation, stress reactivity and psychopathology

According to the fetal origins hypothesis of adaptation and disease, programming of physiological systems by the intrauterine environment equips the fetus for anticipated conditions following birth, but increases risk of disorder if the extra-uterine environment is markedly different. This mismatch hypothesis has proved powerful in the investigation of medical disorders where long term effects of low birth weight on obesity, diabetes, and cardiovascular disease are thought to arise from

Evolutionary perspectives on sex differences and implications for development

Ever since Darwin wrote ‘On The Origin of Species’ sexual selection has been central to the theory of evolution depending “not on a struggle for existence, but on a struggle between the males for possession of the females; the result is not death to the unsuccessful competitor, but few or no offspring” [66]. While there are numerous differences across species, Darwin's generalization has been supported that males, in contrast to females, at certain times give priority to competition and

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Sex differences in the programming effects of prenatal stress on psychopathology and stress responses: An evolutionary perspective

Abstract

Highlights

Introduction

Section snippets

Animal evidence for the differential effects of prenatal stress on males and females

The effects of prenatal stress on child outcome

Stress reactivity

Sex specific differences in placental function

Evolutionary perspectives on fetal adaptation, stress reactivity and psychopathology

Evolutionary perspectives on sex differences and implications for development

J Affect Disord

Neuropharmacology

Psychoneuroendocrinology

Neurosci Biobehav Rev

Psychoneuroendocrinology

Brain Behav Immun

Neuroscience

Neurosci Biobehav Rev

Brain Res Rev

Horm Behav

Exp Neurol

Physiol Behav

European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology

Psychoneuroendocrinology

Physiol Behav

Neurosci Biobehav Rev

J Am Acad Child Adolesc Psychiatry

Biol Psychiatry

Early Hum Dev

Neurosci Biobehav Rev

Psychoneuroendocrinology

Psychoneuroendocrinology

Biol Psychiatry

Neurosci Biobehav Rev

Adolescent self-report of emotional and behavioral problems: interactions of genetic factors with sex and age

J Can Acad Child Adolesc Psychiatry

Sex and age differences in attention-deficit/hyperactivity disorder symptoms and diagnoses: implications for DSM-V and ICD-11

J Am Acad Child Adolesc Psychiatry

Evidence from a large sample of children and adolescents. Journal of Autism and Developmental Disorders

Sex Differences in Autism Spectrum Disorder

Sex differences in the consequences of early-life exposure to epidemiological stress—a life-history approach

Am J Hum Biol

Sex differences in prenatal epigenetic programing of stress pathways

Stress

Minireview: transgenerational inheritance of the stress response: a new frontier in stress research

Endocrinology

Effects of prenatal stress on hypothalamic–pituitary–adrenal (HPA) axis function over two generations of guinea pigs (Cavia aperea f. porcellus)

Gen Comp Endocrinol

Glucocorticoids and sex-dependent development of brain glucocorticoid and mineralocorticoid receptors

Endocrinology

Gender differences in the effects of prenatal stress on brain development and behaviour

Neurochem Res

Sex-dependent changes induced by prenatal stress in cortical and hippocampal morphology and behaviour in rats: an update

Stress

Gestational dexamethasone treatment elicits sex-dependent alterations in locomotor activity, reward-based memory and hippocampal cholinergic function in adolescent and adult rats

Neuropsychopharmacology

Effects of prenatal stress on lever-press acquisition with delayed reinforcement in male and female rats

Behav Processes