112 At a behavioral level, interactions between SERT genotypes and early-life stress have been shown to occur during early development. For example, high levels of maternal anxiety during pregnancy interact with the s allele genotype to increase levels of negative emotionality in infants.113 During the perinatal period, the quality of attachment between

the mother and her baby plays a critical role in controlling the development of emotional regulation in the baby; in conditions of insecure attachment, toddlers carrying the s allele were found to develop poor Inhibitors,research,lifescience,medical self-regulation capacities, a measure indicative of the child’s ability to deliberately control his or her affect and behavior.114 In conditions of low maternal responsiveness infants carrying the s allele displayed decreased levels of attachment to their mothers.115 Maternal care is also modulated by SERT genotypes. Mothers carrying the Inhibitors,research,lifescience,medical s allele display increased maternal sensitivity associated with higher scores on their perceived attachment to their baby,116 supporting the view that the s allele genotype may be linked to increased sensitivity and vigilance to external Inhibitors,research,lifescience,medical stimuli and that during development s allele carriers could be more sensitive to the deleterious effects of early-life adversity. Indeed, a meta-analysis reported

a significant interaction between childhood

maltreatment and the s allele genotype, which can increase the risk for depression later in life,117 although negative results have been reported.118 Discrepancies in the field could be linked to the timing of the gene-environment interaction and the Inhibitors,research,lifescience,medical outcome measure. A recent study indicates Inhibitors,research,lifescience,medical that the s allele PF-4708671 cell line moderates the risk for persistent depressive episodes, but not for single episodes.119 Finally, supportive evidence for interactions between the s allele genotype and early-life stress comes from studies on macaques using a maternal separation design, fn these experimental models, monkeys were separated from their mothers at birth and peer-reared for 6 months. Peer-reared macaques carrying the s allele exhibited more ADAMTS5 aggressive and fearful phenotypes as well as higher levels of HPA stress reactivity and alcohol consumption compared with 1 allele carriers.104,120,121 In addition to SERT, increasing numbers of genetic variants have been shown to interact with early-life stressors and modulate the risk for stress-related psychopathology, including the corticotrophin receptor 1, GR, and FKBP5, a co-chaperone of the GR.122 Among serotonin-related genes, studies have shown that the low activity allele of the MAOA gene interacts with early-life stress to increase risk for aggressive and impulsive phenotypes.