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

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.

Prenatal Alcohol Exposure, FASD, and Child Behavior: A Meta-analysis

“…Articles were scored as 0 if blinding was not mentioned and if it was unclear whether the ASEBA was self-administered. 4 Separate analyses were conducted based on the presence or absence of (1) an FASD diagnosis (including "mixed" groups containing children with PAE in which 100% of them had an FASD diagnosis), and (2) PAE; according to how results were reported in the articles. Data were grouped according to age category (mean age: <5 years, 5-10 years, and >10 years), outcome (ASEBA score), and PAE level where applicable.…”

An examination of sex differences in the effects of early-life opiate and alcohol exposure

“…FASD is associated with deficits in general intelligence, memory, language, attention, learning, executive functioning, motor skills and adaptive functioning [74][75][76]. The effects of FASD also increase the susceptibility of the exposed offspring to develop depression, stress and anxiety disorders later on in life [77].…”

Dihydromyricetin Prevents Fetal Alcohol Exposure-Induced Behavioral and Physiological Deficits: The Roles of GABAA Receptors in Adolescence

“…Previous studies have demonstrated increased anxiety and depressive behaviors in adult FAE rats [60, [80][81][82], however see [83]. Children diagnosed with FASD exhibit high anxiety [84,85], as well as a remarkably high prevalence of epilepsy [86]. While other mechanisms may also be involved, decrements in GABAergic neurotransmission have been associated with increased anxiety [29,30,81] and reduced seizure thresholds [33,87].…”