Acute effects of steroid hormones and neuropeptides on human social–emotional behavior: A review of single administration studies

Abstract

Steroids and peptides mediate a diverse array of animal social behaviors. Human research is restricted by technical–ethical limitations, and models of the neuroendocrine regulation of social–emotional behavior are therefore mainly limited to non-human species, often under the assumption that human social–emotional behavior is emancipated from hormonal control. Development of acute hormone administration procedures in human research, together with the advent of novel non-invasive neuroimaging techniques, have opened up opportunities to systematically study the neuroendocrinology of human social–emotional behavior. Here, we review all placebo-controlled single hormone administration studies addressing human social–emotional behavior, involving the steroids testosterone and estradiol, and the peptides oxytocin and vasopressin. These studies demonstrate substantial hormonal control over human social–emotional behavior and give insights into the underlying neural mechanisms. Finally, we propose a theoretical model that synthesizes detailed knowledge of the neuroendocrinology of social–emotional behavior in animals with the recently gained data from humans described in our review.

Introduction

Ever since Hippocrates introduced the theory on humors in ancient Greece, excesses and shortages of key bodily fluids were traditionally claimed to be responsible for personality characteristics and health problems. Although our current knowledge of human biology holds few similarities to such pre-scientific concepts, were we to exchange ‘neurotransmitters’ and ‘neurohormones’ for the term ‘bodily fluids’, there would be outward resemblances between our modern understanding of factors that control emotions and temperaments, and the classical Hippocratic theories that seem so naive to us today. For instance, it is not uncommon for traditional neurotransmitters such as serotonin and dopamine to be envisioned as key regulators of diverse socio-emotional behaviors and related pathologies (e.g. depression and schizophrenia). A role for peripheral hormones in human social–emotional behavior is however much less acknowledged.

It is generally accepted that diverse social–emotional behaviors in mammals are under control of steroid hormones and neuropeptides. Abundant evidence exists for hormonal control of aggression [71], [125], partner preference [111], maternal bonding [116], social status [168], [213], and sexual behavior [35], but these models are often restricted to non-human species. One reason humans are not included in these models is the suspicion that evolutionarily recent neo-cortical expansions in higher primates, along with cultural evolution in humans during the last several million years [60], [122], have liberated us from such biological constraints. This bias tends to reduce the use of evidence from animal models, much of it based on rodent research, to illuminate what controls behavior in higher mammals, and most especially the human condition. Another key reason for minimizing the importance of such biological factors for illuminating human behavior is the paucity of relevant endocrinological manipulations in well-controlled human research that would permit evaluation of more general cross-species evolutionary principles. Of course, both technical and ethical difficulties often limit causal investigations of relevant endocrine mechanisms in humans, leading to excessive reliance on correlational studies.

Such impediments for the validation of cross-species generalizations are gradually diminishing. Despite difficulties in translational research, the past decade has seen the emergence of potentially powerful new research techniques such as functional brain imaging and grand scale genetic analyses, especially when combined with direct hormone manipulations and conducted along with rigorous psychological analyses, and are leading to the recognition that humans are not immune to the mental influences of many ancestral hormones. These widely available methods, carefully applied, are illuminating the power and fruitfulness of cross-species translational research [109], [135]. Already, the use of new neuroscience techniques and new ways of administering hormones and peptides to humans has led to increased attention and focus on the neuro-endocrine underpinnings of human sociality.

Our aim here is to provide a selective overview of the current status of research involving steroid and peptide regulation of human social–emotional behavior. Furthermore, based on animal research, complemented by recent human studies, we will present a model for the neuroendocrinology of human social–emotional behavior, which describes the behavioral functions of the steroid hormones testosterone (T) and estradiol (E), as well as the neuropeptides oxytocin (OT) and vasopressin (AVP). The model positions the steroids and neuropeptides in a broader functional framework that importantly takes into account environmental influences on hormonal and neuropeptide actions, as well as the role they played through evolution. We hope this model can serve as a heuristic framework for future translational research. But first, we will give a brief overview of the evolutionary trajectory of steroids and peptides, and provide a summary of the social–emotional behaviors these hormones are involved in based on animal studies.