Jack van Honk

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

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.

Exogenous testosterone enhances responsiveness to social threat in the neural circuitry of social aggression in humans

BACKGROUND In a range of species, the androgen steroid testosterone is known to potentiate neural circuits involved in intraspecific aggression. Disorders of impulsive aggression in humans have likewise been associated with high testosterone levels, but human evidence for the link between testosterone and aggression remains correlational and inconclusive. METHODS Twelve female participants underwent functional magnetic resonance imaging during three sessions while viewing stimuli differing in social threat value: angry and happy facial expressions. The first session served to establish associations between baseline hormone levels and neural activation. Participants were retested in a second and third session after placebo-controlled sublingual administration of .5 mg testosterone. RESULTS Findings demonstrate consistent activation to angry versus happy faces in areas known to be involved in vertebrate reactive aggression, such as the amygdala and hypothalamus. Suprathreshold clusters were also found in the orbitofrontal cortex (Brodmann area 47), a region implicated in impulse control in humans. Baseline endocrine profiles of high testosterone and low cortisol were associated with stronger activation in subcortical structures. Neural responses in most activated regions were more persistent after testosterone administration than after placebo. CONCLUSIONS These data demonstrate that testosterone enhances responsiveness in neural circuits of social aggression. Based on animal literature, it is argued that actions of testosterone on subcortical reactive aggression circuits give rise to this effect. Implications for our understanding of the pathophysiology of disorders of impulsive aggression are discussed.

Testosterone shifts the balance between sensitivity for punishment and reward in healthy young women

Animal research has demonstrated reductions in punishment sensitivity and enhanced reward dependency after testosterone administration. In humans, elevated levels of testosterone have been associated with violent and antisocial behavior. Interestingly, extreme forms of violent and antisocial behavior can be observed in the psychopath. Moreover, it has been argued that reduced punishment sensitivity and heightened reward dependency are crucially involved in the etiology and maintenance of psychopathy. A task that has been proven to be capable of simulating punishment-reward contingencies is the IOWA gambling task. Decisions to choose from decks of cards become motivated by punishment and reward schedules inherent in the task. Importantly, clinical and subclinical psychopaths demonstrate a risky, disadvantageous pattern of decision-making in the task, indicating motivational imbalance (insensitivity for punishment and enhanced reward dependency). Here, in a double-blind placebo-controlled crossover design (n = 12), whether a single administration of testosterone would shift the motivational balance between the sensitivity for punishment and reward towards this tendency to choose disadvantageously was investigated. As hypothesized, subjects showed a more disadvantageous pattern of decision-making after testosterone compared to placebo administration. These findings not only provide the first direct evidence for the effects of testosterone on punishment-reward contingencies in humans, but they also give further insights into the hypothetical link between testosterone and psychopathy.

Correlations among Salivary Testosterone, Mood, and Selective Attention to Threat in Humans

An experiment was designed to investigate the relation among salivary testosterone, mood, and selective attention to threat. The participant group consisted of 32 nonclinical subjects (16 men and 16 women). Individuals completed the Profile Of Mood States (POMS) and performed a pictorial emotional Stroop task measuring selective attention to angry faces. Anticipating a time lag between testosterone (as measured in saliva) and cognitive emotional behavior, multiple time-coursed saliva samples were taken preceding the assessment of questionnaire and task for every subject. In both sexes, salivary testosterone was significantly related to mood (i.e., anger and tension) and selective attention to angry faces when saliva samples were taken 6 h before questionnaire and task assessment. Research on the relation between testosterone and human behavior might benefit by taking into account time lags between the behavioral manifestations and the continuously changing levels of testosterone.

Testosterone administration impairs cognitive empathy in women depending on second-to-fourth digit ratio

During social interactions we automatically infer motives, intentions, and feelings from bodily cues of others, especially from the eye region of their faces. This cognitive empathic ability is one of the most important components of social intelligence, and is essential for effective social interaction. Females on average outperform males in this cognitive empathy, and the male sex hormone testosterone is thought to be involved. Testosterone may not only down-regulate social intelligence organizationally, by affecting fetal brain development, but also activationally, by its current effects on the brain. Here, we show that administration of testosterone in 16 young women led to a significant impairment in their cognitive empathy, and that this effect is powerfully predicted by a proxy of fetal testosterone: the right-hand second digit-to-fourth digit ratio. Our data thus not only demonstrate down-regulatory effects of current testosterone on cognitive empathy, but also suggest these are preprogrammed by the very same hormone prenatally. These findings have importance for our understanding of the psychobiology of human social intelligence.

Testosterone Reduces Unconscious Fear but Not Consciously Experienced Anxiety: Implications for the Disorders of Fear and Anxiety

BACKGROUND The fear-reducing properties of testosterone have been firmly established in animals but not in humans. However, human data on the relation between testosterone, fear, and anxiety have predominantly involved questionnaires that index cortically executed conscious appraisal of anxious mood. Animal studies, on the other hand, indicate that the effects of testosterone on motivation and emotion are of subcortical origin and of unconscious nature. Presently, it was hypothesized that a single testosterone administration to humans would reduce unconscious fear but not consciously experienced anxiety. METHODS In a placebo-controlled, double-blind crossover design, a single dose of testosterone (.5 mg) or placebo was administered to 16 healthy female volunteers. Afterward, a masked emotional Stroop task measured unconscious emotional responses to fearful faces, while multiple self-reports of mood indexed consciously experienced anxiety. RESULTS As hypothesized, the habitual vigilant emotional response to the masked fearful face observed in the placebo condition was significantly reduced after testosterone was administered, while the self-reported measures of anxiety remained unaffected. CONCLUSIONS These data provide the first direct evidence for fear-reducing properties of testosterone in humans. Furthermore, by dissociating specific aspects of fear and anxiety in humans, this outcome highlights that testosterones effects on motivation and emotion concern the subcortical affective pathways of the brain.

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.

Attentional biases for angry faces: Relationships to trait anger and anxiety

In two experiments selective attention to angry faces was investigated in relation to trait anger and anxiety. A pictorial emotional Stroop task comparing colour-naming latencies for neutral and angry faces was employed. In Experiment 1 using an unmasked task, individuals scoring high on trait anger showed an attentional bias for angry faces. In Experiment 2, unmasked and masked versions of the task were used. Individuals were selected on low and high trait anxiety, but there was no indication of a relation between attentional bias scores and anxiety. When individuals were subsequently reallocated to groups on the basis of trait anger scores, the high anger group showed an attentional bias for angry faces in the unmasked and the masked task. Results are discussed in relation to recent neurobiological findings from our laboratory, as reflecting an evolutionary-evolved, content-specific response to the facial expression of anger.

A single administration of testosterone reduces fear-potentiated startle in humans

BACKGROUND Ample evidence from animal research indicates that the gonadal steroid hormone testosterone has fear-reducing properties. Human data on this topic, however, are scarce and far less unequivocal. The present study therefore aimed to scrutinize anxiolytic effects of a single dose of testosterone, using a direct physiological index of fear in humans. METHODS Twenty healthy female participants were tested in a double-blind, placebo-controlled crossover design involving sublingual administration of a single dose of testosterone. Four hours after intake, we assessed effects on baseline startle and fear-potentiated startle in a verbal threat-of-shock paradigm. RESULTS In accordance with predictions, testosterone administration resulted in reduced fear-potentiated startle, without affecting baseline startle. CONCLUSIONS This study provides direct evidence that a single dose of testosterone reduces fear in humans. The relationship of this effect to previous research on anxiolytic effects of benzodiazepines, as well as possible mechanisms of action, is discussed.

A single administration of testosterone improves visuospatial ability in young women

Previous research has documented correlations between endogenous testosterone levels and visuospatial cognitive function. Some causal relations have also been established in treatment designs in which testosterone was administered to elderly subjects for a number of weeks. Particularly, one study reported a selective effect of a single administration of testosterone on some aspects of spatial memory in 15 women. The present study tested the hypothesis whether a single administration of 0.5 mg of sublingual testosterone would improve visuospatial ability in healthy young women on a test that has consistently been associated with male superiority. Twenty-six women participated in a double-blind placebo-controlled cross-over trial of single administration of testosterone and placebo. Subjects were tested in the same phase of the menstrual-cycle. Four to five hours after both administrations, subjects completed a standardized measure of visuospatial ability (3-D Mental Rotations Test). Visuospatial ability improved significantly after testosterone administration compared to placebo, after controlling for learning effects due to repeated testing. Testosterone is suggested to be causally related to visuospatial ability in young women.