Amygdala Gene Expression Correlates of Social Behavior in Monkeys Experiencing Maternal Separation

Abstract

Children exposed to early parental loss from death or separation carry a greater risk for developing future psychiatric illnesses, such as major depression and anxiety. Monkeys experiencing maternal separation at 1 week of age show fewer social behaviors and an increase in self-comforting behaviors (e.g., thumb sucking) over development, whereas in contrast, monkeys experiencing maternal separation at 1 month of age show increased seeking of social comfort later in life. We sought to identify neural systems that may underlie these stress-induced behavioral changes by examining changes in mRNA content in amygdala tissue collected from 1 week separated, 1 month separated, and maternally reared infants at 3 months of age. mRNA from the right medial temporal lobe, primarily the amygdala, was analyzed using Affymetrix U133A 2.0 arrays. One gene, guanylate cyclase 1 ␣ 3 (GUCY1A3), showed differential expression between the 1 week and maternally reared groups and the 1 week and 1 month groups; these changes were confirmed by in situ hybridization. The expression of this gene was positively correlated with acute social-comforting behavior (r ϭ 0.923; p ϭ 0.001) and longer-term close social behavior (r ϭ 0.708; p ϭ 0.015) and negatively correlated with self-comforting behaviors (r ϭ Ϫ0.88; p Ͻ 0.001). Additional in situ hybridization studies of GUCY1A3 in normal monkeys showed that this gene is expressed at adult levels by 1 week of age and that its expression is greater in the amygdala than all other brain areas examined. We conclude that GUCY1A3 may contribute to the altered behavioral phenotypes that are differentially displayed depending on the age at which macaque infants experience an early-life stress.

Central amygdala nucleus (Ce) gene expression linked to increased trait-like Ce metabolism and anxious temperament in young primates

“…Importantly, early-life FGF2 treatment also enhanced adult neurogenesis, which was accompanied by increased hippocampal expression of NTRK3 (55). Moreover, primate research has demonstrated that neurodevelopmentally relevant gene expression in the amygdala is altered by prolonged maternal separation (57). Taken together, these data are consistent with our demonstration that monkeys with lower levels of AT show greater Ce expression of NTRK3 and further motivate mechanistic research into the role for neurodevelopmentally important transcripts in the development of AT.…”

The Neural Basis of Self-Touch in a Pain-Free Situation

“…In monkeys, infants deprived of their mothers exhibit a striking decrease in social interactions with others and an increase in self-comforting behaviors [1][2][3]. In adults, nonverbal "selfadaptors" are unintentional movements that involve self-touching behaviors such as stroking or rubbing one's own hand, and are associated with a lack of conscious awareness, occurring in response to situational anxiety and stress [4][5][6][7][8].…”

Larger amygdala but no change in hippocampal volume in 10-year-old children exposed to maternal depressive symptomatology since birth

“…For example, poor caregiving in rodents results in acceleration of amygdala development (9,10), increases in corticotrophin-releasing hormone-containing neurons (11), and sensitization of the amygdala in adolescence (12). In addition, nonhuman primate studies show that maternal separation alters amygdala development, and that this effect is more devastating when maternal separation occurs earlier in life (13).…”