Socioeconomic status and the brain: mechanistic insights from human and animal research

Abstract

Human brain development occurs within a socioeconomic context and childhood socioeconomic status (SES) influences neural development--particularly of the systems that subserve language and executive function. Research in humans and in animal models has implicated prenatal factors, parent-child interactions and cognitive stimulation in the home environment in the effects of SES on neural development. These findings provide a unique opportunity for understanding how environmental factors can lead to individual differences in brain development, and for improving the programmes and policies that are designed to alleviate SES-related disparities in mental health and academic achievement.

Figure 1. Parental regulation of the hypothalamic–pituitary–adrenal axis

a | The current working model for the effect of maternal care (specifically, of licking and grooming pups) on the epigenetic regulation of the expression of Nr3c1, the gene that encodes the glucocorticoid receptor (GR). Licking and grooming of pups activates thyroid hormone-dependent increases in hippocampal serotonin (5-hydroxytryptamine or 5-HT) levels and 5-HT binding to the 5-HT₇ receptor. Activation of the 5-HT₇ receptor leads to the activation of a cyclic AMP–protein kinase A (PKA) cascade that induces the expression of the transcription factor nerve growth factor-inducible A (NGFIA) and cyclic AMP response element-binding (CREB) protein (CBP) expression and their association with the neuron-specific exon 1₇ GR gene promoter. b | in neonates, high levels of licking increases NGFIA and CBP association with the exon 1₇ promoter by triggering demethylation of a dinucleotide sequence (CpG) that is located within the NGFIA binding region of the exon. This subsequently increases the ability of NGFIA to activate GR gene expression. M, methylation. c | A schematic of the hypothalamic–pituitary–adrenal axis, the pivot of which are the corticotropin-releasing factor (CRF) neurons of the paraventricular nucleus of the hypothalamus. CRF is released into the portal system of the anterior pituitary, stimulating the synthesis and release of adrenocorticotropin (ACTH), which then stimulates adrenal glucocorticoid release. Glucocorticoids act on GRs in multiple brain regions, including the hippocampus, to inhibit the synthesis and release of cRF (that is, glucocorticoid negative feedback takes place). The adult offspring of mothers that exhibit high licking and grooming, by comparison to those of low licking and grooming dams, show increased GR expression, enhanced negative-feedback sensitivity to glucocorticoids, reduced CRF expression in the hypothalamus and more modest pituitary–adrenal responses to stress.