Prenatal alcohol exposure: Fetal programming and later life vulnerability to stress, depression and anxiety disorders

doi:10.1016/j.neubiorev.2009.06.004

Neuroscience & Biobehavioral Reviews

Volume 34, Issue 6, May 2010, Pages 791-807

https://doi.org/10.1016/j.neubiorev.2009.06.004 Get rights and content

Abstract

Children with fetal alcohol spectrum disorder (FASD) exhibit cognitive, neuropsychological and behavioral problems, and numerous secondary disabilities including depression and anxiety disorders. Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis is common in depression/anxiety, reflected primarily in increased HPA tone or activity. Prenatal alcohol exposure (PAE) increases HPA tone and results in HPA dysregulation throughout life, paralleling many of the HPA changes in depression/anxiety. We review data demonstrating altered HPA function and increased depression/anxiety in FASD. In the context of the stress-diathesis model, we discuss the hypothesis that fetal programming of the HPA axis by PAE alters neuroadaptive mechanisms that mediate the stress response, thus sensitizing the organism to stressors encountered later in life, and mediating, at least partly, the increased vulnerability to depression/anxiety disorders. Furthermore, we present evidence demonstrating sex-specific alterations in both hormonal and behavioral responsiveness to tasks measuring depressive- and anxiety-like behaviors in PAE offspring. Overall, the research suggests that the stress-diathesis model provides a powerful approach for elucidating mechanisms underlying the increased vulnerability to mental illness among individuals with FASD, and developing appropriate treatments for these individuals. Dr. Seymour Levine's seminal work on the long-term consequences of early life experiences formed a framework for the development of the research described in this review.

Section snippets

FASD: description in humans and animal models

Fetal alcohol spectrum disorder (FASD) is an umbrella term that describes the range of adverse effects that can occur in children born to women who consume alcohol during pregnancy (Manning and Hoyme, 2007, Riley and McGee, 2005). At the most severe end of the spectrum is fetal alcohol syndrome (FAS), which can occur with chronic consumption of high doses of alcohol (Jones and Smith, 1973, Jones et al., 1973). The diagnostic criteria for FAS include pre- and post-natal growth retardation,

Overview

Depression is a highly prevalent, chronic, recurring, and potentially life-threatening illness (Berton and Nestler, 2006, Nestler et al., 2002). Severe forms of depression affect at least 2–5% of the US population, and up to 20% of the population are affected by milder forms of depression (Nestler et al., 2002). A survey by the World Health Organization indicates that depression is one of the top 10 causes of morbidity and mortality worldwide (Berton and Nestler, 2006). There is a strong

The monoamine hypothesis

The monoamine hypothesis has been the dominant one in the depression field for many years. This hypothesis states that a deficiency in serotonergic (5-HT) and noradrenergic (NA) transmission underlies the symptoms of depression (Schildkraut, 1965). It is based primarily on the serendipitous finding that drugs that facilitate monoaminergic transmission can be effective antidepressants (Hindmarch, 2002, Nestler et al., 2002). However, over the years it has become apparent that one must go beyond

Fetal programming

Although the etiology of depression/anxiety disorders is at present unknown, it is generally accepted that the incidence of these mental illnesses occurs in greater proportion among vulnerable populations. One possible explanation for this could relate to early (pre- and early postnatal) adverse experience. The concept of fetal programming developed originally from a large body of data showing that low birth weight and other indices of poor fetal growth are associated with increased biological

Modelling prenatal alcohol exposure

In our well-established model of prenatal alcohol (ethanol) exposure (Weinberg, 1985, Weinberg, 1988, Weinberg, 1989), pregnant dams are assigned to one of three treatment groups. The ethanol (PAE) treatment group is offered liquid ethanol diet (36% ethanol-derived calories) ad libitum, formulated to provide adequate nutrition to pregnant rats regardless of ethanol intake (Weinberg, 1985). The pair-fed (PF) group is offered a liquid control diet with maltose-dextrin isocalorically substituted

Prenatal alcohol exposure and depressive-/anxiety-like symptoms

Although there are clear parallels between the neurobiological alterations observed in PAE animals and what is observed in human depression and anxiety disorders, our ability to model these disorders effectively is limited if we do not take into consideration the functional consequences of changes in central circuits. To explore this issue, we have utilized an animal model of chronic mild stress (CMS) to investigate the effects of prenatal alcohol exposure on vulnerability to depression/anxiety

Prenatal alcohol exposure as early adverse experience

Taken together, our recent studies demonstrate that (1) our modified CMS procedure is successful in altering both behavioral and endocrine measures of activity in a manner parallel in many respects to that observed in depressive-/anxiety-like disorders; (2) exposure of PAE animals to stressors (CMS) in adulthood increases depressive- and anxiety-like behaviors relative to those in C animals, and does so in a sexually dimorphic manner. PAE males exposed to CMS showed greater anxiety (EPM),

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Prenatal alcohol exposure (PAE) can reprogram the development of cells and tissues, resulting in a spectrum of physical and neurobehavioral teratology. PAE immediately impacts fetal growth, but its effects carry forward post-parturition, into adolescence and adulthood, and can result in a cluster of disabilities, collectively termed Fetal Alcohol Spectrum Disorders. Emerging preclinical and clinical research investigating neurological and behavioral outcomes in exposed offspring point to genetic sex as an important modifier of the effects of PAE. In this review, we discuss the literature on sex differences following PAE, with studies spanning the fetal period through adulthood, and highlight gaps in research where sex differences are likely, but currently under-investigated. Understanding how sex and PAE interact to affect offspring health outcomes across the lifespan is critical for identifying the full complement of PAE-associated secondary conditions, and for refining targeted interventions to improve the quality of life for individuals with PAE.
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ReviewPrenatal alcohol exposure: Fetal programming and later life vulnerability to stress, depression and anxiety disorders

Abstract

Section snippets

FASD: description in humans and animal models

Overview

The monoamine hypothesis

Fetal programming

Modelling prenatal alcohol exposure

Prenatal alcohol exposure and depressive-/anxiety-like symptoms

Prenatal alcohol exposure as early adverse experience

Pharmacol. Biochem. Behav.

Physiol. Behav.

Physiol. Behav.

Eur. J. Pharmacol.

Biomed. Pharmacother.

Front. Neuroendocrinol.

Horm. Behav.

Pharmacol. Biochem. Behav.

Neurosci. Biobehav. Rev.

Anim. Behav.

Brain Res. Brain Res. Rev.

Behav. Brain Res.

Psychiatr. Clin. North Am.

Neurotoxicol. Teratol.

Biol. Psychiatry

Behav. Brain Res.

Biol. Psychiatry

Neurotoxicol. Teratol.

Pharmacol. Biochem. Behav.

Neurosci. Biobehav. Rev.

Neuroscience

Recent Prog. Horm. Res.

Biol. Psychiatry

Eur. Psychiatry

Psychoneuroendocrinology

Appetite

Physiol. Behav.

Physiol. Behav.

Dev. Brain Res.

Psychoneuroendocrinology

J. Nutr.

Trends Endocrinol. Metab.

Physiol. Behav.

Psychiatr. Res.

Eur. Psychiatry

Pharmacol. Biochem. Behav.

Neuropsychopharmacology

J. Affect. Disord.

Prog. Neuropsychopharmacol. Biol. Psychiatry

Physiol. Behav.

Lancet

Effects of prenatal alcohol exposure on growth and development in rats

J. Pharmacol. Exp. Ther.

Metabolic rate in the right amygdala predicts negative affect in depressed patients

Neuroreport

Negative regulation of corticotropin releasing factor expression and limitation of stress response

Stress

Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR

The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Commentary and review

Arch. Gen. Psychiatry

Neuropyschological and behavioral outcomes from a comprehensive magnetic resonance study of children

Can. J. Clin. Pharmacol.

Implication of the hypothalamic–pituitary–adrenal axis in the physiopathology of depression

J. Psychiatry Neurosci.

Interaction between serotonin transporter gene variation and rearing condition in alcohol preference and consumption in female primates

Arch. Gen. Psychiatry

Relationship of childhood maltreatment to the onset and course of major depression in adulthood

Depress. Anxiety

Review
Prenatal alcohol exposure: Fetal programming and later life vulnerability to stress, depression and anxiety disorders