Peter Putman

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.

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.

Testosterone administration reduces empathetic behavior: A facial mimicry study

Although high baseline testosterone levels correlate with low empathy, there is no causal evidence for this association in humans. The present study tested the causality of this relationship by manipulating testosterone levels in a double-blind placebo controlled crossover design. 20 healthy female participants received either a sublingual administration of a single dose of testosterone or placebo on 2 days and were tested 4 h after administration. Because research has shown that facial expression mimicry is a non-obtrusive index of empathy, facial electromyography was measured in response to dynamic facial expressions of happy and angry faces. Results showed that testosterone generally decreased facial mimicry. These findings are consistent with models that assign a critical role to mimicry in the ability to develop and communicate empathy towards conspecifics, and provide a potential causal mechanism of effects of testosterone on empathy.

Defective somatic markers in sub-clinical psychopathy

Damasios somatic marker hypothesis is argued to be specifically applicable to psychopathy, though evidence has been meager until now. The principal evidence for the somatic marker hypothesis is based on findings in patients with orbitofrontal lesions, showing absent punishment learning on the Iowa gambling task. Interestingly, neuroimaging studies indicate orbitofrontal dysfunction in psychopathy also. Here we investigated the somatic marker hypothesis in subjects selected on low and high psychopathic behavioral characteristics from the outer extreme ranges of a large subject pool (n  = 525). The low psychopathic subject group (n  = 16) showed intact punishment learning, suggesting somatic markers came to guide their decisions in the course of the game. In contrast, such punishment learning was not observed in the high psychopathic subject group (n  = 16), who mimicked the gambling behavior of orbitofrontal patients. These findings provide further evidence for the hypothesized link between psychopathy and orbitofrontal dysfunction.

Emotional Stroop Performance for Masked Angry Faces: It's BAS, Not BIS.

Theoretical models concerning selective attention to emotional stimuli predict heightened vigilance to angry faces in people with heightened trait anxiety or greater activity of the Behavioral Inhibition System (BIS). Recent evidence from electroencephalographic lateralization and affect studies and from studies assessing attentional biases to angry faces suggest, however, that heightened anger and activity of the Behavioral Activation System (BAS) should predict vigilant responding to angry faces. Social anxiety should predict avoidance of angry faces. Results from a masked emotional Stroop task verified these hypotheses, but an unmasked emotional Stroop provided no reliable relations. This dissociation confirms earlier claims that masked emotional Stroop performance is impervious to conscious control over the cognitive-emotional processes, as measured by the Stroop task.

Exogenous testosterone attenuates the integrated central stress response in healthy young women.

Animal research has shown that the androgen steroid testosterone, the end product of the hypothalamic-pituitary-gonadal (HPG) axis, down regulates the integrated stress response at multiple levels. These effects have been demonstrated at the level of the amygdala and the bed nucleus of the stria terminalis, and along the different nodes of the hypothalamic-pituitary-adrenal (HPA) axis. The present study was designed to assess effects of exogenous testosterone upon reactivity of the autonomic nervous system and modulation of the acoustic startle reflex in humans. Twenty healthy female participants received double-blind, placebo-controlled sublingual administrations of .5mg testosterone. Measurements were made of phasic electrodermal activity, cardiac responses, and startle reflexes to acoustic probes while participants were exposed to pictures with strongly aversive, neutral, or positive content. Subjective reports of mood and picture evaluations were also obtained. Results support the hypothesis of a generally decreased responsiveness of the stress system by showing reduced skin conductance responses as well as reduced affective startle modulation in anxiety-prone participants after administration of testosterone. Candidate neurobiological mechanisms of action are outlined and discussed, and it is argued that androgens promote dynamic regulation of the stress system through actions upon central neuropeptidergic pathways that control corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) expression. The present findings highlight the importance of further investigation of the possible role of the HPG axis in disorders that are associated with HPA axis dysfunctions.

Gaze direction differentially affects avoidance tendencies to happy and angry faces in socially anxious individuals

Increasing evidence indicates that eye gaze direction affects the processing of emotional faces in anxious individuals. However, the effects of eye gaze direction on the behavioral responses elicited by emotional faces, such as avoidance behavior, remain largely unexplored. We administered an Approach-Avoidance Task (AAT) in high (HSA) and low socially anxious (LSA) individuals. All participants responded to photographs of angry, happy and neutral faces (presented with direct and averted gaze), by either pushing a joystick away from them (avoidance) or pulling it towards them (approach). Compared to LSA, HSA were faster in avoiding than approaching angry faces. Most crucially, this avoidance tendency was only present when the perceived anger was directed towards the subject (direct gaze) and not when the gaze of the face-stimulus was averted. In contrast, HSA individuals tended to avoid happy faces irrespectively of gaze direction. Neutral faces elicited no approach-avoidance tendencies. Thus avoidance of angry faces in social anxiety as measured by AA-tasks reflects avoidance of subject-directed anger and not of negative stimuli in general. In addition, although both anger and joy are considered to reflect approach-related emotions, gaze direction did not affect HSAs avoidance of happy faces, suggesting differential mechanisms affecting responses to happy and angry faces in social anxiety.

A single administration of cortisol acutely reduces preconscious attention for fear in anxious young men.

Chronically elevated HPA activity has often been associated with fear and anxiety, but there is evidence that single administrations of glucocorticoids may acutely reduce fear. Moreover, peri-traumatic cortisol elevation may protect against development of post-traumatic stress disorder. Hypervigilant processing of threat information plays a role in anxiety disorders and although relations with HPA functioning have been established, causality of these relations remains unclear. Presently, self-reported anxiety and response time patterns on a masked emotional Stroop task with fearful faces were measured in 20 healthy young men after double-blind, placebo-controlled oral administration of 40 mg cortisol. The masked fearful Stroop task measures vocal colornaming response latencies for pictures of neutral and fearful faces presented below the threshold for conscious perception. Results showed increased response times on trials for fearful compared to neutral faces after placebo, but this emotional Stroop effect was acutely abolished by cortisol administration. This effect was most pronounced in subjects with heightened anxiety levels. This is the first evidence showing that exogenous cortisol acutely reduces anxiety-driven selective attention to threat. These results extend earlier findings of acute fear reduction after glucocorticoid administration. This suggests interactions of HPA functioning and vigilant attention in the pathogenesis of anxiety disorders. Possible neuroendocrine mechanisms of action are discussed.

Effects of single cortisol administrations on human affect reviewed: Coping with stress through adaptive regulation of automatic cognitive processing

The human stress hormone cortisol may facilitate effective coping after psychological stress. In apparent agreement, administration of cortisol has been demonstrated to reduce fear in response to stressors. For anxious patients with phobias or posttraumatic stress disorder this has been ascribed to hypothetical inhibition of retrieval of traumatic memories. However, such stress-protective effects may also work via adaptive regulation of early cognitive processing of threatening information from the environment. This paper selectively reviews the available literature on effects of single cortisol administrations on affect and early cognitive processing of affectively significant information. The concluded working hypothesis is that immediate effects of high concentration of cortisol may facilitate stress-coping via inhibition of automatic processing of goal-irrelevant threatening information and through increased automatic approach-avoidance responses in early emotional processing. Limitations in the existing literature and suggestions for future directions are briefly discussed.

EEG theta/beta ratio in relation to fear-modulated response-inhibition, attentional control, and affective traits

Power density-ratios of fast and slow frequency spectrum-bands can be calculated from resting-state electroencephalography (EEG) recordings. A well-established phenomenon is that slow wave/fast wave ratios (SW/FW) are increased in attention-deficit/hyperactivity disorder. Several researchers have also begun to study relationships between SW/FW and affect. This work suggests that increased SW/FW may reflect reduced frontal cortical control over subcortical affective approach drive. The present study (n=28) aimed to further examine this notion by testing several predictions derived from it. In line with these predictions, SW/FW was found to correlate negatively with fearful modulation of response inhibition in an emotional go/no-go task and with self-reported attentional control. Results also suggested a positive relation between SW/FW and trait approach motivation and a negative relation to anxiety, as predicted. These results are consistent with previous studies and support the notion that SW/FW may provide a useful tool in the study of affect and emotion regulation.