Socioeconomic disadvantage experienced in early development predicts ill health in adulthood. However, the neurobiological pathways linking early disadvantage to adult health remain unclear. Lower parental education-a presumptive indicator of early socioeconomic disadvantage-predicts health-impairing adult behaviors, including tobacco and alcohol dependencies. These behaviors depend, in part, on the functionality of corticostriatal brain systems that 1) show developmental plasticity and early vulnerability, 2) process reward-related information, and 3) regulate impulsive decisions and actions. Hence, corticostriatal functionality in adulthood may covary directly with indicators of early socioeconomic disadvantage, particularly lower parental education. Here, we tested the covariation between parental education and corticostriatal activation and connectivity in 76 adults without confounding clinical syndromes. Corticostriatal activation and connectivity were assessed during the processing of stimuli signaling monetary gains (positive feedback [PF]) and losses (negative feedback). After accounting for participants' own education and other explanatory factors, lower parental education predicted reduced activation in anterior cingulate and dorsomedial prefrontal cortices during PF, along with reduced connectivity between these cortices and orbitofrontal and striatal areas implicated in reward processing and impulse regulation. In speculation, adult alterations in corticostriatal functionality may represent facets of a neurobiological endophenotype linked to socioeconomic conditions of early development.

Inconsistent or null findings among studies associating behaviors on the externalizing spectrum--addictions, impulsivity, risk-taking, novelty-seeking traits--with presence of the 7-repeat allele of a common length polymorphism in the gene encoding the dopamine D4 receptor (DRD4) may stem from individuals' variable exposures to prominent environmental moderators (gene × environment interaction). Here, we report that relative preference for immediate, smaller rewards over larger rewards delayed in time (delay discounting), a behavioral endophenotype of impulsive decision-making, varied by interaction of DRD4 genotype with childhood socioeconomic status (SES) among 546 mid-life community volunteers. Independent of age, sex, adulthood SES and IQ, participants who were both raised in families of distinctly low SES (low parental education and occupational grade) and carried the DRD4 7-repeat allele discounted future rewards more steeply than like-reared counterparts of alternate DRD4 genotype. In the absence of childhood socioeconomic disadvantage, however, participants carrying the 7-repeat allele discounted future rewards less steeply. This bidirectional association of DRD4 genotype with temporal discounting, conditioned by participants' early life circumstances, accords with a recently proposed developmental model of gene × environment interaction ('differential susceptibility') that posits genetically modulated sensitivity to both adverse and salubrious environmental influences.

Age at menarche, a sentinel index of pubertal maturation, was examined in relation to early family relationships (conflict, cohesion) and polymorphic variation in the gene encoding estrogen receptor-α (ESR1) in a midlife sample of 455 European American women. Consistent with prior literature, women who reported being raised in families characterized by close interpersonal relationships and little conflict tended to reach menarche at a later age than participants reared in families lacking cohesion and prone to discord. Moreover, this association was moderated by ESR1 variation, such that quality of the family environment covaried positively with menarcheal age among participants homozygous for minor alleles of the two ESR1 polymorphisms studied here (rs9304799, rs2234693), but not among women of other ESR1 genotypes. In addition, a) family relationship variables were unrelated to ESR1 variation, and b) genotype-dependent effects of childhood environment on age at menarche could not be accounted for by personality traits elsewhere shown to explain heritable variation in reported family conflict and cohesion. These findings are consistent with theories of differential susceptibility to environmental influence, as well as the more specific hypothesis (by Belsky) that girls differ genetically in their sensitivity to rearing effects on pubertal maturation.