Prenatal iron deficiency and monoamine oxidase A (MAOA) polymorphisms: combined risk for later cognitive performance in rhesus monkeys

Abstract

Monoamine oxidase A (MAOA) gene polymorphisms resulting in high and low transcription rates are associated with individual differences in reward efficacy and response inhibition. Iron deficiency (ID) is the most frequent single-nutrient deficiency worldwide, and prenatal ID has recently been shown to carry a risk for lower mental development scores in infants. In this study, a potential interaction of MAOA genotype and prenatal ID was studied in young male rhesus monkeys. Cognitive tasks, including problem solving, responsiveness to reward and attention, were used to characterize the potential interaction of these two fetal risks. ID was induced by feeding rhesus monkey dams an iron-deficient (10 ppm, ID) or an iron-sufficient (100 ppm, IS) diet during gestation (n = 10/group). Subgroups of the ID and IS diet offspring had low-MAOA or high-MAOA transcription rate polymorphisms. ID combined with low-MAOA genotype showed distinctive effects on reward preference and problem solving while ID in hi-MAOA juveniles modified response inhibition. Given the incidence of ID and MAOA polymorphisms in humans, this interaction could be a significant determinant of cognitive performance.

Fig. 1

Performance of cognitive tests reflecting interactions of MAOA genotype (low or high transcription rates) and dietary iron (iron sufficient (IS) or iron deficient (ID). a, b Performance is similar in the two genotype groups with an iron-sufficient diet, but diverges with iron deficiency. c, d Performance differs in the two genotype groups with an iron-sufficient diet but converges with iron deficiency. In all 4 tasks, the direction of the effect of ID is consistent within genotype group, increasing performance measures in the hi-MAOA group and decreasing them in the low-MAOA group. * indicates statistically significant genotype by ID interaction