David Terburg

Testosterone, cortisol, and serotonin as key regulators of social aggression: A review and theoretical perspective

In human and non-human animals the steroid hormones cortisol and testosterone are involved in social aggression and recent studies suggest that these steroids might jointly regulate this behavior. It has been hypothesized that the imbalance between cortisol and testosterone levels is predictive for aggressive psychopathology, with high testosterone to cortisol ratio predisposing to a socially aggressive behavioral style. In this review, we focus on the effects of cortisol and testosterone on human social aggression, as well as on how they might modulate the aggression circuitry of the human brain. Recently, serotonin is hypothesized to differentiate between impulsive and instrumental aggression, and we will briefly review evidence on this hypothesis. The aim of this article is to provide a theoretical framework for the role of steroids and serotonin in impulsive social aggression in humans.

The testosterone–cortisol ratio: A hormonal marker for proneness to social aggression

Social aggression is an escalating hazard for individuals and society. It is most frequently observed as impulsive-reactive aggression in antisocial personality disorder (APD), but in psychopathic aggressive personalities instrumental social aggression is more prominent. However, the psychobiological mechanisms underlying human social aggression are still poorly understood. Here we propose a psychobiological mechanism that may explain human social aggression wherein the steroid hormones cortisol and testosterone play a critical role. High levels of testosterone and low levels of cortisol have been associated with social aggression in several species but it seems that in those individuals wherein these hormonal markers combine social aggression is most violent. In this review we discuss fundamental and clinical research which underscores the potential of the testosterone-cortisol ratio as a possible marker for criminal aggressive tendencies.

Testosterone decreases trust in socially naïve humans

Trust plays an important role in the formation and maintenance of human social relationships. But trusting others is associated with a cost, given the prevalence of cheaters and deceivers in human society. Recent research has shown that the peptide hormone oxytocin increases trust in humans. However, oxytocin also makes individuals susceptible to betrayal, because under influence of oxytocin, subjects perseverate in giving trust to others they know are untrustworthy. Testosterone, a steroid hormone associated with competition and dominance, is often viewed as an inhibitor of sociality, and may have antagonistic properties with oxytocin. The following experiment tests this possibility in a placebo-controlled, within-subjects design involving the administration of testosterone to 24 female subjects. We show that compared with the placebo, testosterone significantly decreases interpersonal trust, and, as further analyses established, this effect is determined by those who give trust easily. We suggest that testosterone adaptively increases social vigilance in these trusting individuals to better prepare them for competition over status and valued resources. In conclusion, our data provide unique insights into the hormonal regulation of human sociality by showing that testosterone downregulates interpersonal trust in an adaptive manner.

New evidence on testosterone and cooperation

arising from C. Eisenegger, M. Naef, R. Snozzi, M. Heinrichs & E. Fehr 463, 356–359 (2010)10.1038/nature08711; Eisenegger et al. replyIn February 2010, Eisenegger et al. reported increased fair bargaining behaviour after administration of testosterone in an ultimatum game. However, unfair offers in the ultimatum game typically are rejected; thus, not only the motives for social cooperation but also the threat of financial punishment may have accounted for these effects. Here, using the public goods game (PGG), we unambiguously show increased social cooperation after testosterone administration, but only among subjects with low levels of prenatal testosterone (measured by the right hand’s second-to-fourth-digit ratio (2D:4D)). This finding establishes positive effects of testosterone on social cooperation, with prenatal hormonal priming providing for important individual variability.

Testosterone Affects Gaze Aversion From Angry Faces Outside of Conscious Awareness

Throughout vertebrate phylogeny, testosterone has motivated animals to obtain and maintain social dominance—a fact suggesting that unconscious primordial brain mechanisms are involved in social dominance. In humans, however, the prevailing view is that the neocortex is in control of primordial drives, and testosterone is thought to promote social dominance via conscious feelings of superiority, indefatigability, strength, and anger. Here we show that testosterone administration in humans prolongs dominant staring into the eyes of threatening faces that are viewed outside of awareness, without affecting consciously experienced feelings. These findings reveal that testosterone motivates social dominance in humans in much the same ways that it does in other vertebrates: involuntarily, automatically, and unconsciously.

Hypervigilance for fear after basolateral amygdala damage in humans

Recent rodent research has shown that the basolateral amygdala (BLA) inhibits unconditioned, or innate, fear. It is, however, unknown whether the BLA acts in similar ways in humans. In a group of five subjects with a rare genetic syndrome, that is, Urbach–Wiethe disease (UWD), we used a combination of structural and functional neuroimaging, and established focal, bilateral BLA damage, while other amygdala sub-regions are functionally intact. We tested the translational hypothesis that these BLA-damaged UWD-subjects are hypervigilant to facial expressions of fear, which are prototypical innate threat cues in humans. Our data indeed repeatedly confirm fear hypervigilance in these UWD subjects. They show hypervigilant responses to unconsciously presented fearful faces in a modified Stroop task. They attend longer to the eyes of dynamically displayed fearful faces in an eye-tracked emotion recognition task, and in that task recognize facial fear significantly better than control subjects. These findings provide the first direct evidence in humans in support of an inhibitory function of the BLA on the brains threat vigilance system, which has important implications for the understanding of the amygdalas role in the disorders of fear and anxiety.

Approach–Avoidance versus Dominance–Submissiveness: A Multilevel Neural Framework on How Testosterone Promotes Social Status

Approach–avoidance generally describes appetitive motivation and fear of punishment. In a social context approach motivation is, however, also expressed as social aggression and dominance. We therefore link approach–avoidance to dominance–submissiveness, and provide a neural framework that describes how the steroid hormone testosterone shifts reflexive as well as deliberate behaviors towards dominance and promotion of social status. Testosterone inhibits acute fear at the level of the basolateral amygdala and hypothalamus and promotes reactive dominance through upregulation of vasopressin gene expression in the central-medial amygdala. Finally, the hormone can, depending on social context and prenatal hormone exposure, promote both pro- and antisocial behaviors and decisions through its effects on prefrontal–amygdala interactions. All these effects of testosterone, however, serve to increase and maintain social status.

Testosterone administration modulates moral judgments depending on second-to-fourth digit ratio

Moral judgment involves the interplay of emotions and social cognitions. The male sex-hormone testosterone might play a role in moral reasoning as males are more utilitarian than females in their moral decisions, and high salivary testosterone levels also are associated with utilitarian moral decisions. However, there is no direct evidence for a role of testosterone in moral reasoning. Recent testosterone administration studies show effects on cognitive empathy and social cooperation, which depend on right-hands second-to-fourth (2D:4D) digit ratio, a proxy for prenatal sex-hormone (testosterone-versus-estradiol) priming. Here, in a placebo-controlled within-subjects design using 20 young females we show that 2D:4D predicts 44% of the variance in the effects of testosterone administration on moral judgment. Subjects who show an increase in utilitarian judgments following testosterone administration have significantly higher than average 2D:4D (relatively high prenatal estradiol priming), while subjects showing more deontological judgments following testosterone administration have near-significantly lower 2D:4D (relatively high prenatal testosterone priming). We argue that prenatally-organized differences in aromatase, i.e. conversion from testosterone to estradiol in the brain, might underlie these effects. Our findings suggest that early neurodevelopmental effects of sex steroids play a crucial role in the activational effects of hormones on moral reasoning later in life.

Eye Tracking Unconscious Face-to-Face Confrontations Dominance Motives Prolong Gaze to Masked Angry Faces

In primates, dominance/submission relationships are generally automatically and nonaggressively established in face-to-face confrontations. Researchers have argued that this process involves an explicit psychological stress-manipulation mechanism: Striding with a threatening expression, while keeping direct eye contact, outstresses rivals so that they submissively avert their gaze. In contrast, researchers have proposed a reflexive and implicit modulation of face-to-face confrontation in humans, on the basis of evidence that dominant and submissive individuals exhibit vigilant and avoidant responses, respectively, to facial anger in masked emotional Stroop tasks. However, these tasks do not provide an ecologically valid index of gaze behavior. Therefore, we directly measured gaze responses to masked angry, happy, and neutral facial expressions with a saccade-latency paradigm and found that increased dominance traits predict a more prolonged gaze to (or reluctance to avert gaze from) masked anger. Furthermore, greater non-dominance-related reward sensitivity predicts more persistent gaze to masked happiness. These results strongly suggest that implicit and reflexive mechanisms underlie dominant and submissive gaze behavior in face-to-face confrontations.

Cortisol administration induces global down-regulation of the brain's reward circuitry

Research in rodents and humans has shown divergent effects of the glucocorticoids corticosterone and cortisol (CRT) on reward processing. In rodents, administration of CRT increases reward drive by facilitating dopamine release in the ventral striatum. In humans, correspondingly, risky decision-making increases when CRT levels are elevated. Human stress studies contrariwise show that elevated CRT is accompanied by a decrease in reward-related brain activity. There are however no direct insights into how CRT acts on the reward system in the human brain. Accordingly, we used pharmacological functional magnetic resonance imaging (pharmaco-fMRI) to investigate the effects of CRT on the brains reward system. In a randomized within-subject design we administered a high dose of CRT (40 mg) and placebo to twenty healthy male volunteers on separate days, and used a monetary incentive delay task to assess the effects of the hormone on the striatum and the amygdala in anticipation of potential reward. In contrast to animal studies, we show that this high dose of CRT strongly decreases activity of the striatum in both reward and non-reward conditions. Furthermore, we observed reductions in activity in the basolateral amygdala, a key regulator of the brains reward system. Crucially, the overall down-regulation of the brains reward circuit was verified on the subjective level as subjects reported significantly reduced reward preference after CRT. In sum, we provide here direct evidence in humans that CRT acts on brain regions involved in reward-related behavior, that is, the basolateral amygdala and the striatum. Our findings suggest that CRT in the quantity and time course presently used globally down-regulates the reward system, and thereby decreases motivational processing in general.