Biobehavioral markers of adverse effect in fetal alcohol spectrum disorders

Abstract

Identification of children with fetal alcohol spectrum disorders (FASD) is difficult because information regarding prenatal exposure is often lacking, a large proportion of affected children do not exhibit facial anomalies, and no distinctive behavioral phenotype has been identified. Castellanos and Tannock have advocated going beyond descriptive symptom-based approaches to diagnosis to identify biomarkers derived from cognitive neuroscience. Classical eyeblink conditioning and magnitude comparison are particularly promising biobehavioral markers of FASD-eyeblink conditioning because a deficit in this elemental form of learning characterizes a very large proportion of alcohol-exposed children; magnitude comparison because it is a domain of higher order cognitive function that is among the most sensitive to fetal alcohol exposure. Because the neural circuitry mediating both these biobehavioral markers is well understood, they have considerable potential for advancing understanding of the pathophysiology of FASD, which can contribute to development of treatments targeted to the specific deficits that characterize this disorder.

Fig. 1

Schematic diagram of trial epochs used in delay and trace conditioning

Fig. 2

Simplified diagram of the cerebellar memory circuit of the essential circuitry for classical eyeblink conditioning (adapted from Christian and Thompson 2003)

Fig. 3

Percent conditioned responses in each block by fetal alcohol spectrum disorders diagnostic group (a) at 5 years and (b) at 11 years. Error bars are standard error of the mean. Blocks 1 to 5 = Session 1; Blocks 6 to 10 = Session 2 (N=81 (40 males; 37 females) at 5 years; N=63 (23 males; 40 females) at 11 years)

Fig. 4

Path model examining the degree to which the relation of prenatal alcohol exposure to the Calculation composite score is mediated by Magnitude Comparison