Judy L. Cameron

Interrelationships between Hormones, Behavior, and Affect during Adolescence: Understanding Hormonal, Physical, and Brain Changes Occurring in Association with Pubertal Activation of the Reproductive Axis. Introduction to Part III

Abstract: This paper summarizes the goals of this section and considers current knowledge about the association between hormonal changes that occur over pubertal development and the changes in behavior and brain function over the adolescent period. It reviews the cascade of neural and hormonal changes that occur with puberty; discusses mechanisms by which these changes can affect higher‐order brain processes; reviews the current limited state of knowledge about links between puberty and changes in affect regulation in the adolescent period; identifies hurdles that have made progress in our understanding of these relationships difficult; and suggests areas for future investigation that will allow us to obtain a much more comprehensive understanding of these interrelationships. This overview of the physiological processes occurring at puberty indicates that puberty (1) encompasses changes in a number of neural systems; (2) results in altered secretion of a number of hormones; (3) involves hormones that are secreted in a pulsatile manner so that collection of a single blood sample does not clearly delineate hormone profiles; and (4) shows considerable individual variation in the rate of progression and in hormone secretion during progression. The important role that gonadal steroid hormones play throughout development and adulthood in regulating plastic changes in neuronal structure and function is noted, highlighting the need for further studies to determine the extent to which the dramatic increases in circulating steroid hormones at puberty modulate brain circuits that underlie changes in social behaviors, risk‐taking behaviors, and cognitive function at adolescence.

Interrelationships between Hormones, Behavior, and Affect during Adolescence: Complex Relationships Exist between Reproductive Hormones, Stress‐Related Hormones, and the Activity of Neural Systems That Regulate Behavioral Affect. Comments on Part III

Abstract: Adolescence is a period in life marked by change, encompassing physiological changes associated with pubertal development, changes in social status and the social stresses that an individual faces, and changes in behavioral affect regulation. The interactions between activity in the reproductive axis, the neural systems that regulate stress, hormones produced in response to stress, and neural systems governing behavioral affect regulation are complex and multifaceted. Although our understanding of these interactions remains rudimentary, we do know that stress can suppress activity of the reproductive axis, that reproductive hormones can modulate the activity of neural systems that govern the bodys responses to stress, that both reproductive function and stress responsiveness can be altered in depressed individuals, and that the function of some of the key neural systems regulating behavioral affect (i.e., serotonergic, noradrenergic, dopaminergic systems) are modulated by both gonadal steroid hormones and adrenal steroid hormones. This summary reviews the central interactions discussed in this session on the interrelationships between hormones, behavior, and affect during adolescence and identifies key topics that require further investigation in order to understand the role that pubertal changes in reproductive function, interacting with increased exposure to life stresses, play in modulating behavioral affect regulation during the adolescent period.

Designing new microsatellite markers for linkage and population genetic analyses in rhesus macaques and other nonhuman primates.

Identification of polymorphic microsatellite loci in nonhuman primates is useful for various biomedical and evolutionary studies of these species. Prior methods for identifying microsatellites in nonhuman primates are inefficient. We describe a new strategy for marker development that uses the available whole genome sequence for rhesus macaques. Fifty-four novel rhesus-derived microsatellites were genotyped in large pedigrees of rhesus monkeys. Linkage analysis was used to place 51 of these loci into the existing rhesus linkage map. In addition, we find that microsatellites identified this way are polymorphic in other Old World monkeys such as baboons. This approach to marker development is more efficient than previous methods and produces polymorphisms with known locations in the rhesus genome assembly. Finally, we propose a nomenclature system that can be used for rhesus-derived microsatellites genotyped in any species or for novel loci derived from the genome sequence of any nonhuman primate.

Mapping of the serotonin transporter locus (SLC6A4) to rhesus chromosome 16 using genetic linkage

man primates also contains repetitive elements in the upstream promoter region (Lesch et al., 1997). Rhesus monkeys (Macaca mulatta) exhibit a common repeat unit polymorphism that is similar in structure and located close to the human repeat polymorphism, but the allelic variation among rhesus monkeys is not identical to the human polymorphism. Nevertheless, the polymorphism in rhesus also has functional effects. Trefi lov et al. (2000) found that free-ranging rhesus monkeys carrying two copies of the short allele (s) dispersed from their natal groups at an earlier age than did either the carriers of two long alleles (l) or heterozygotes. Bennett et al. (2002) showed that the rhesus polymorphism (l vs. s) alters in vitro gene expression in this species as well, and that when animals are raised in peer groups (as opposed to motherreared), the SLC6A4 polymorphism can infl uence levels of serotonin metabolites found in the cerebrospinal fl uid. Champoux et al. (2002) found that variation in the temperament of infant rhesus macaques is associated with SLC6A4 genotype. More recently, Barr et al. (2004) found an interaction between SLC6A4 genotype and early rearing experience that regulates activation of HPA axis stress response. Bethea et al. (2004) showed that infant rhesus monkeys that carry the s/s genotype exhibit increases in certain fear responses and are behaviorally inhibited when challenged with a series of tests involving stimuli that induce mild fear or anxiety. Clearly, individual variation in the SLC6A4 gene can infl uence individual variation in several aspects of neurobiology, stress reactivity and expressed behavior. The goal of the present study is to establish the chromosomal position of the SLC6A4 gene within the rhesus genome. As part of a larger program in comparative primate genomics, Rationale and signifi cance