Rearing condition and rh5-HTTLPR interact to influence limbic-hypothalamic-pituitary-adrenal axis response to stress in infant macaques.

Laboratory of Clinical Studies, National Institute of Alcoholism and Alcohol Abuse, National Institutes of Health, Poolesville, Maryland 20837, USA.
Biological Psychiatry (Impact Factor: 9.47). 05/2004; 55(7):733-8. DOI: 10.1016/j.biopsych.2003.12.008
Source: PubMed

ABSTRACT In humans and macaques, a promoter polymorphism that decreases transcription of the serotonin transporter gene is associated with anxiety. Serotonin transporter gene disruption in rodents produces anxious animals with exaggerated limbic-hypothalamic-pituitary-adrenal (LHPA) responses to stress. We wanted to determine whether serotonin transporter gene promoter variation (rh-5HTTLPR) and rearing condition would interact to influence endocrine responses to stress in infant rhesus macaques.
Animals were reared with their mothers (MR, n = 141) or in peer-only groups (PR, n = 67). At 6 months of age, adrenocorticotropic hormone (ACTH) and cortisol levels were determined at baseline and during separation stress. Serotonin transporter genotype (l/l and l/s) was determined with polymerase chain reaction followed by gel electrophoresis.
Cortisol levels increased during separation, and there was a main effect of rearing condition, with decreased cortisol levels among PR macaques. Animals with l/s rh5-HTTLPR genotypes had higher ACTH levels than did l/l animals. Adrenocorticotropic hormone levels increased during separation, and there was a separation x rearing x rh5-HTTLPR interaction, such that PR-l/s animals had higher ACTH levels during separation than did other animals studied.
These data demonstrate that serotonin transporter gene variation affects LHPA axis activity and that the influence of rh5-HTTLPR on hormonal responses during stress is modulated by early experience.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human behavioral sex differences are ubiquitous, but the degree to which these sex differences are evolved or culturally invented is hotly contested across disciplines. A review of the human research yields strong evidence that somatic and social causes are both important in human behavioral sex differentiation, but researchers in this area struggle to agree on the relative importance of each. Understanding the social and somatic determinants of nonhuman primate sex-typed development may shed light on the relative responsibility of social and somatic causes of human behavioral sex differentiation. A review of this research (and related research on the proximate drivers of nonhuman primate behavioral development more generally) indicates that primate behavioral sex differentiation is rooted in somatic causes, but that these are situated in and cannot be extricated from social influences. Overt gender socialization and phenomena such as gender performance seem to be uniquely human. Primate research using a dynamic systems theoretical approach to behavioral development has the greatest potential to further clarify the workings of human behavioral sex differentiation, and further primate research is indispensable for understanding the evolution of human sex-typed behavior. Yrbk Phys Anthropol, 2014. © 2014 Wiley Periodicals, Inc.
    American Journal of Physical Anthropology 02/2015; 156. DOI:10.1002/ajpa.22660 · 2.51 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Complex human traits are likely to be affected by many environmental and genetic factors, and the interactions among them. However, previous gene-environment interaction (G×E) studies have typically focused on one or only a few genetic variants at a time. To provide a broader view of G×E, this study examines the relationship between 403 genetic variants from 39 genes and youth delinquency and violence. We find evidence that low social control is associated with greater genetic risk for delinquency and violence and high/moderate social control with smaller genetic risk for delinquency and violence. Our findings are consistent with prior G×E studies based on a small number of genetic variants, and, more importantly, we show that these findings still hold when a large number of genetic variants are considered simultaneously. A key implication of these findings is that the expression of multiple genes related to delinquency depends on the social environment: gene expression is likely to be amplified in low-social-control environments but, tends to be suppressed in high/moderate-social-control environments. This study not only deepens our understanding of how the social environment shapes individual behavior, but also provides important conceptual and methodological insights for future G×E research on complex human traits.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Research efforts during the past decades have provided intriguing evidence suggesting that stressful experiences during pregnancy exert long-term consequences on the future mental wellbeing of both the mother and her baby. Recent human epidemiological and animal studies indicate that stressful experiences in utero or during early life may increase the risk of neurological and psychiatric disorders, arguably via altered epigenetic regulation. Epigenetic mechanisms, such as miRNA expression, DNA methylation, and histone modifications are prone to changes in response to stressful experiences and hostile environmental factors. Altered epigenetic regulation may potentially influence fetal endocrine programming and brain development across several generations. Only recently, however, more attention has been paid to possible transgenerational effects of stress. In this review we discuss the evidence of transgenerational epigenetic inheritance of stress exposure in human studies and animal models. We highlight the complex interplay between prenatal stress exposure, associated changes in miRNA expression and DNA methylation in placenta and brain and possible links to greater risks of schizophrenia, attention deficit hyperactivity disorder, autism, anxiety - or depression-related disorders later in life. Based on existing evidence, we propose that prenatal stress, through the generation of epigenetic alterations, becomes one of the most powerful influences on mental health in later life. The consideration of ancestral and prenatal stress effects on lifetime health trajectories is critical for improving strategies that support healthy development and successful aging.
    Neuroscience & Biobehavioral Reviews 11/2014; 48. DOI:10.1016/j.neubiorev.2014.11.013 · 10.28 Impact Factor