Introduction to the Special Issue on Gene-Hormone Interplay

Hormones are messengers — signaling molecules that transmit information from cell to cell and from tissue to tissue (Cooper, 2000). Unlike neurotransmitters, which travel only across the infinitesimal synaptic cleft, hormones can travel to distant tissues in the body, e.g., from the brain to the genitals and back again. The word “hormone” is derived from the Greek word for “impetus.” Fitting that description, hormones are driving forces for growth and behavior; they impel and inhibit eating, drinking, mood changes, mating, fleeing, and fighting. We chose the title “Gene-Hormone Interplay” for this Special Issue because it is a general term that encompasses the variety of roles that hormones may play in the complex link between genotype and behavioral phenotypes. The most straightforward relationship between genes and hormones is simply that genes code for hormones, for hormone receptors, for hormone precursors, and for molecules necessary for hormonal synthesis, transport, and elimination. In fact, many of the specific genes involved in hormonal signaling have already been identified. For example, the CRH gene codes for corticotrophin-releasing hormone, which is synthesized in and released from the hypothalamus as part of the hypothalamus-pituitary-adrenal-gland cascade that ultimately results in the release of cortisol as part of the human stress response. The behavioral genetic study of hormones is, in some ways, in the opposite position as the behavior genetic study of complex behavior. For cognitive ability or depression, we know generally how much population variation is due to genetic differences between people, but we are largely ignorant about which specific genes make up that effect. For hormones, we know which specific genes code for the key components of hormonal systems, but we are largely ignorant of whether variation in those genes accounts for much of the observed phenotypic variation in hormone levels. Two papers in this Special Issue (Van Hulle, Moore, Shirtcliff, Lemery-Chalfant, and Goldsmith, 2015; Estourgie-van Burk, Bartels, Boomsma, 2015) present data on the heritabilities of hormone levels during adolescence and are thus filling critical gaps in the literature. One obvious but understudied question is how and if hormone-relevant genes are related to behavioral phenotypes. Illustrating this approach, two companion papers in this Special Issue examine the effects of a specific gene, Srd5a1, which is involved in the synthesis of allopregnanolone (a neuroactive steroid that is synthesized from progesterone), on alcohol use behavior in an animal model (Ford, Nickel, Kaufman, and Finn, 2015; Tanchuck-Nipper et al., 2015). Two other papers use family designs to examine the links between hormonal processes and (latent) genetic risks for psychopathology. Marceau and colleagues (2015) use an adoption design to examine if genetic risk for psychopathology, as indexed by biological mothers’ substance use, externalizing, and internalizing problems, was linked with children’s morning cortisol levels. Additionally, Corley, Beltz, Wadsworth, and Berenbaum (2015) use a longitudinal twin design to examine if genetic risk for adolescent substance use is linked with genetic influences on pubertal development. Not only do genes code for hormones, but hormones regulate genes. In particular, steroid hormones (such as cortisol, estradiol, progesterone, and testosterone) bind to intracellular receptors that act as genetic transcription factors that directly regulate gene expression. For this reason, one emerging area of research is gene-by-hormone interactions: Do hormonal changes (such as experienced in puberty) activate or suppress the genetic influences on a behavioral phenotype via changes in gene expression? In this Special Issue, this question is explored in a paper by Corley et al. who test whether genetic influences on internalizing and externalizing symptoms increase after mid-puberty. In sum, hormones are potential mediators and moderators of genetic influences on behavior, yet behavioral genetic research on gene-hormone interplay is a field of study that is still in its infancy. This Special Issue presents a series of papers that present intriguing — and sometimes surprising — findings that offer an early glimpse into a burgeoning and important field of study. Spanning the lifespan from the prenatal period through middle adulthood, these papers point the way toward new avenues of discovery in behavioral genetic research.