ABSTRACT
Rewards are a broad category of stimuli inducing approach behavior to aid survival. Extensive evidence from animal research has shown that wanting (the motivation to pursue a reward) and liking (the pleasure associated with its consumption) are mostly regulated by dopaminergic and opioidergic activity in dedicated brain areas. However, less is known about the neuroanatomy of dopaminergic and opioidergic regulation of reward processing in humans, especially when considering different types of rewards (i.e., social and nonsocial). To fill this gap of knowledge, we combined dopaminergic and opioidergic antagonism (via amisulpride and naltrexone administration) with functional neuroimaging to investigate the neurochemical and neuroanatomical bases of wanting and liking of matched nonsocial (food) and social (interpersonal touch) rewards, using a randomized, between-subject, placebo-controlled, double-blind design. While no drug effect was observed at the behavioral level, brain activity was modulated by the administered compounds. In particular, opioid antagonism, compared to placebo, reduced activity in the medial orbitofrontal cortex during consumption of the most valued social and nonsocial rewards. Dopamine antagonism, however, had no clear effects on brain activity in response to reward anticipation. These findings provide insights into the neurobiology of human reward processing and suggest a similar opioidergic regulation of the neural responses to social and nonsocial reward consumption.
Subject(s)
Dopamine , Narcotic Antagonists , Animals , Humans , Narcotic Antagonists/pharmacology , Emotions , Touch , Receptors, OpioidABSTRACT
The ability to learn about other people is crucial for human social functioning. Dopamine has been proposed to regulate the precision of beliefs, but direct behavioural evidence of this is lacking. In this study, we investigate how a high dose of the D2/D3 dopamine receptor antagonist sulpiride impacts learning about other people's prosocial attitudes in a repeated Trust game. Using a Bayesian model of belief updating, we show that in a sample of 76 male participants sulpiride increases the volatility of beliefs, which leads to higher precision weights on prediction errors. This effect is driven by participants with genetically conferred higher dopamine availability (Taq1a polymorphism) and remains even after controlling for working memory performance. Higher precision weights are reflected in higher reciprocal behaviour in the repeated Trust game but not in single-round Trust games. Our data provide evidence that the D2 receptors are pivotal in regulating prediction error-driven belief updating in a social context.
Subject(s)
Dopamine Antagonists , Sulpiride , Humans , Male , Dopamine , Trust , Bayes Theorem , Receptors, Dopamine D3/genetics , Receptors, Dopamine D2ABSTRACT
Humans are strategically more prosocial when their actions are being watched by others than when they act alone. Using a psychopharmacogenetic approach, we investigated the endocrinological and computational mechanisms of such audience-driven prosociality. One hundred and ninety-two male participants received either a single dose of testosterone (150 mg) or a placebo and performed a prosocial and self-benefitting reinforcement learning task. Crucially, the task was performed either in private or when being watched. Rival theories suggest that the hormone might either diminish or strengthen audience-dependent prosociality. We show that exogenous testosterone fully eliminated strategic, i.e., feigned, prosociality and thus decreased submission to audience expectations. We next performed reinforcement-learning drift-diffusion computational modeling to elucidate which latent aspects of decision-making testosterone acted on. The modeling revealed that testosterone compared to placebo did not deteriorate reinforcement learning per se. Rather, when being watched, the hormone altered the degree to which the learned information on choice value translated to action selection. Taken together, our study provides novel evidence of testosterone's effects on implicit reward processing, through which it counteracts conformity and deceptive reputation strategies.
Subject(s)
Altruism , Testosterone , Humans , Male , Choice Behavior , Reinforcement, Psychology , Reward , Social Behavior , Testosterone/pharmacologyABSTRACT
Human behaviour requires flexible arbitration between actions we do out of habit and actions that are directed towards a specific goal. Drugs that target opioid and dopamine receptors are notorious for inducing maladaptive habitual drug consumption; yet, how the opioidergic and dopaminergic neurotransmitter systems contribute to the arbitration between habitual and goal-directed behaviour is poorly understood. By combining pharmacological challenges with a well-established decision-making task and a novel computational model, we show that the administration of the dopamine D2/3 receptor antagonist amisulpride led to an increase in goal-directed or 'model-based' relative to habitual or 'model-free' behaviour, whereas the non-selective opioid receptor antagonist naltrexone had no appreciable effect. The effect of amisulpride on model-based/model-free behaviour did not scale with drug serum levels in the blood. Furthermore, participants with higher amisulpride serum levels showed higher explorative behaviour. These findings highlight the distinct functional contributions of dopamine and opioid receptors to goal-directed and habitual behaviour and support the notion that even small doses of amisulpride promote flexible application of cognitive control.
Subject(s)
Dopamine , Narcotic Antagonists , Humans , Amisulpride , Healthy Volunteers , Dopamine D2 Receptor Antagonists/pharmacology , Receptors, OpioidABSTRACT
Art, as a prestigious cultural commodity, concerns aesthetic and monetary values, personal tastes, and social reputation in various social contexts-all of which are reflected in choices concerning our liking, or in other contexts, our actual willingness-to-pay for artworks. But, how do these different aspects interact in regard to the concept of social reputation and our private versus social selves, which appear to be essentially intervening, and potentially conflicting, factors driving choice? In our study, we investigated liking and willingness-to-pay choices using-in art research-a novel, forced-choice paradigm. Participants (N = 123) made choices from artwork-triplets presented with opposing artistic quality and monetary value-labeling, thereby creating ambiguous choice situations. Choices were made in either private or in social/public contexts, in which participants were made to believe that either art-pricing or art-making experts were watching their selections. A multi-method design with eye-tracking, neuroendocrinology (testosterone, cortisol), and motivational factors complemented the behavioral choice analysis. Results showed that artworks, of which participants were told were of high artistic value were more often liked and those of high monetary-value received more willingness-to-pay choices. However, while willingness-to-pay was significantly affected by the presumed observation of art-pricing experts, liking selections did not differ between private/public contexts. Liking choices, compared to willingness-to-pay, were also better predicted by eye movement patterns. Whereas, hormone levels had a stronger relation with monetary aspects (willingness-to-pay/ art-pricing expert). This was further confirmed by motivational factors representative for reputation seeking behavior. Our study points to an unexplored terrain highlighting the linkage of social reputation mechanisms and its impact on choice behavior with a ubiquitous commodity, art.
Subject(s)
Art , Motivation , Choice Behavior , Emotions , Humans , TasteABSTRACT
The sex hormone estradiol is hypothesized to play a key role in human cognition, and reward processing specifically, via increased dopamine D1-receptor signalling. However, the effect of estradiol on reward processing in men has never been established. To fill this gap, we performed a double-blind placebo-controlled study in which men (N = 100) received either a single dose of estradiol (2 mg) or a placebo. Subjects performed a probabilistic reinforcement learning task where they had to choose between two options with varying reward probabilities to maximize monetary reward. Results showed that estradiol administration increased reward sensitivity compared to placebo. This effect was observed in subjects' choices, how much weight they assigned to their previous choices, and subjective reports about the reward probabilities. Furthermore, effects of estradiol were moderated by reward sensitivity, as measured through the BIS/BAS questionnaire. Using reinforcement learning models, we found that behavioral effects of estradiol were reflected in increased learning rates. These results demonstrate a causal role of estradiol within the framework of reinforcement learning, by enhancing reward sensitivity and learning. Furthermore, they provide preliminary evidence for dopamine-related genetic variants moderating the effect of estradiol on reward processing.
Subject(s)
Estradiol , Reinforcement, Psychology , Dopamine , Double-Blind Method , Estradiol/pharmacology , Humans , Learning , Male , RewardABSTRACT
Recent research suggests that when we lack a sense of control, we are prone to motivational failures and early quitting in competitions. Testosterone, on the other hand, is thought to boost competitiveness. Here we investigate the interaction between these factors, testing the testosterone's potential to enhance persistence in a competition against a stronger opponent, depending on experimentally manipulated perceived control. Healthy participants were administered a single dose of testosterone or placebo. They first underwent a task designed to either induce low or high perceived control and then entered a costly competition against a progressively stronger opponent that they could quit at any time. In the placebo group, men with low perceived control quitted twice as early as those with high perceived control. Testosterone countered this effect, making individuals with low control persist in the competition for as long as those with high perceived control, and did so also despite raising participants' explicit awareness of the opponents' advantage. This psychoendocrinological effect was not modulated by basal cortisol levels, CAG repeat polymorphism of the androgen receptor gene, or trait dominance. Our results provide the first causal evidence that testosterone promotes competitive persistence in humans and demonstrate that this effect depends on the psychological state elicited prior to the competition, broadening our understanding of the complex relationships between testosterone and social behaviors.
Subject(s)
Competitive Behavior , Testosterone , Competitive Behavior/physiology , Humans , MaleABSTRACT
The observation of animal orofacial and behavioral reactions has played a fundamental role in research on reward but is seldom assessed in humans. Healthy volunteers (N = 131) received 400 mg of the dopaminergic antagonist amisulpride, 50 mg of the opioidergic antagonist naltrexone, or placebo. Subjective ratings, physical effort, and facial reactions to matched primary social (affective touch) and nonsocial (food) rewards were assessed. Both drugs resulted in lower physical effort and greater negative facial reactions during reward anticipation, especially of food rewards. Only opioidergic manipulation through naltrexone led to a reduction in positive facial reactions to liked rewards during reward consumption. Subjective ratings of wanting and liking were not modulated by either drug. Results suggest that facial reactions during anticipated and experienced pleasure rely on partly different neurochemical systems, and also that the neurochemical bases for food and touch rewards are not identical.
Studies in rats and other species have shown that two chemical messengers in the brain regulate how much an animal desires a reward, and how pleasant receiving the reward is. In this context, chemicals called opioids control both wanting and enjoying a reward, whereas a chemical called dopamine only regulates how much an animal desires it. However, since these results were obtained from research performed on animals, further studies are needed to determine if these chemicals play the same roles in the human brain. Korb et al. show that the same brain chemicals that control reward anticipation and pleasure in rats are also at work in humans. In the experiment, 131 healthy volunteers received either a drug that blocks opioid signaling in the brain, a drug that blocks dopamine signaling, or a placebo, a pill with no effect. Then, participants were given, on several occasions, either sweet milk with chocolate or a gentle caress on the forearm. Participants rated how much they wanted each of the rewards before receiving it, and how much they liked it after experiencing it. To measure their implicit wanting of the reward, participants also pressed a force-measuring device to increase their chances of receiving the reward. Additionally, small electrodes measured the movement of the volunteer's smiling or frowning muscles to detect changes in facial expressions of pleasure. Volunteers taking either drug pressed on the device less hard than the participants taking the placebo, suggesting they did not want the rewards as much, and they frowned more as they anticipated the reward, indicating less anticipatory pleasure. However, only the volunteers taking the opioid-blocking drug smiled less when they received a reward, indicating that these participants did not get as much pleasure as others out of receiving it. These differences were most pronounced when volunteers looked at or received the sweet milk with chocolate. This experiment helps to shed light on the chemicals in the human brain that are involved in reward-seeking behaviors. In the future, the results may be useful for developing better treatments for addictions.
Subject(s)
Amisulpride/administration & dosage , Dopamine Antagonists/administration & dosage , Naltrexone/administration & dosage , Narcotic Antagonists/administration & dosage , Pleasure/drug effects , Reward , Adult , Emotions/drug effects , Female , Food , Humans , Male , Young AdultABSTRACT
Higher testosterone levels in males have previously been linked to decreased stress reactivity, but in other cases, testosterone has been reported to increase the stress response. We addressed these inconsistencies in a placebo-controlled single-dose testosterone administration study, in which 120 male participants were randomly assigned to undergo a cold-pressor test (CPT, a non-social somatic stressor), a socially evaluated cold-pressor test (SECPT, a social-somatic stressor), or a lukewarm water test (LWT, a non-stressful control condition). Throughout the experiment, blood pressure and interbeat intervals were measured continuously, and saliva samples for hormonal analyses were taken repeatedly at predefined time points. When comparing the groups treated with placebo, the SECPT elicited a larger increase in the systolic blood pressure than CPT, in agreement with previous studies. However, testosterone administration altered this pattern. Compared to placebo, testosterone increased systolic blood pressure during the CPT, whereas the opposite effect was found during the SECPT. Cortisol reactivity was not affected by testosterone administration. The CAG repeat polymorphism of the androgen receptor gene was unrelated to the effects of testosterone on the stress response, but it was correlated with blood pressure across the whole sample. Our findings demonstrate that testosterone's effects on the stress response are dependent on the social context. Testosterone's ability to flexibly influence the response to stressors may be an important mechanism through which the hormone promotes adaptive behavior. Our results are also in line with research showing that testosterone decreases social anxiety and suggest it may help to modulate the effects of stress in socially challenging situations.
Subject(s)
Blood Pressure/drug effects , Heart Rate/drug effects , Hydrocortisone/metabolism , Social Behavior , Stress, Psychological/metabolism , Stress, Psychological/physiopathology , Testosterone/pharmacology , Adult , Humans , Male , Testosterone/administration & dosage , Young AdultABSTRACT
Persisting even when the rewards of continued effort are fading is essential for achieving long-term goals, skills, and good health, alike. Yet, we often quit when things get hard. Here, we tested whether augmenting the feeling of control through external measures increases persistence under such discouraging circumstances. In two laboratory experiments, we first induced illusory control by manipulating the base-rate of positive outcomes and then tested the effect of this elevation of participants' perceived control upon their persistence under diminishing returns and in a competition against a stronger opponent. Induced illusory control significantly enhanced people's persistence in both of these motivationally challenging situations. Our findings demonstrate that motivation is dependent upon perceived, rather than objective, control, and reveal that this can be leveraged to counteract quitting behavior when things get hard, for instance in rehabilitation, physical activity interventions, or other training settings.
Subject(s)
Achievement , Competitive Behavior , Illusions , Internal-External Control , Motivation , Reward , Self Efficacy , Adult , Aged , Female , Goals , Humans , Male , Middle AgedABSTRACT
Whether cognitive, motivational and hedonic aspects of reward anticipation and consumption can be reliably assessed with explicit and implicit measures, and if different motivational (decision utility) and hedonic (experienced utility) processes get recruited by distinct reward types, remain partly unsolved questions that are relevant for theories of social and non-social decision-making. We investigated these topics using a novel experimental paradigm, including carefully matched social and nonsocial rewards, and by focusing on facial responses. Facial expressions are indeed an often-cited implicit measure of rewards' hedonic impact. For example, food rewards elicit powerful facial responses - characterized by lip smacking, tongue protrusion, and relaxation of the middle face - in human newborns, juvenile monkeys, and adult rats. The same stimuli elicit more nuanced facial reactions in adult humans, which can be best captured with facial electromyography (fEMG). However, little is known about facial expressions preceding reward consumption, reflecting the motivation to obtain and possibly the expected pleasantness of a reward, and whether similar facial expressions are elicited by different types of rewards. To investigate these questions, a novel within-subject experimental paradigm was developed. During the anticipation and consumption of social (affective touch) and nonsocial (food) rewards, explicit (ratings of wanting and liking, physical effort) and implicit (fEMG) measures of wanting and liking were taken in 43 healthy adult participants. Reduced activation of the Corrugator Supercilii (CS) muscle (reflecting less frowning and indicating greater positive response) was found in trials with higher wanting and effort during the anticipation of food rewards, as well as in trials with higher liking and effort during the consumption of food rewards. The CS muscle is thus a sensitive measure of wanting and liking of food rewards both during their anticipation and consumption. Crucially, thanks to careful reward matching, these results cannot be explained by differences in subjective wanting, liking, or effort produced to obtain the two types of rewards. No significant modulation of the Zygomaticus Major (ZM) muscle was found for social or food rewards. Explorative analyses however indicated that the ZM may activate during the delivery of the most wanted touch, but not for the most wanted food. The absence of significant effects of social rewards on the activation of CS and ZM muscles are discussed in relation to the specifics of this innovative task comparing two types of matched rewards in the same participants. The present findings contribute to the understanding of the processes underlying motivational and hedonic aspects of rewards, and may therefore inform models of social and non-social decision-making.
Subject(s)
Anticipation, Psychological/physiology , Facial Expression , Facial Muscles/physiology , Food , Motivation/physiology , Pleasure/physiology , Reward , Social Interaction , Touch Perception/physiology , Adult , Electromyography , Female , Humans , Male , Young AdultABSTRACT
Trust and betrayal are central to our social world, and adaptive responses to generous and selfish behavior are crucial to our economic and social well-being [1]. We learn about others' trustworthiness through trial and error during repeated interactions [2]. By reinforcing and suppressing behavior during positive and negative interactions with conspecifics, rodent research has established a crucial role for the basolateral amygdala (BLA) in social experiential learning [3, 4]. The human BLA has undergone a reorganization with massive expansion relative to other amygdala nuclei [5], and there is no translational research on its role in experiential learning. The human amygdala is traditionally researched as a single structure [6], neglecting the sub-nuclei's structural und functional differences [7], which might explain inconsistent findings in research on social interactions [8, 9]. Here, we study whether the human BLA is necessary for social and non-social experiential learning by testing a group of five humans with selective bilateral damage to the BLA. We compared their learning behavior in a repeated trust game, and a non-social control task, to healthy, matched controls. Crucially, BLA-damaged subjects, unlike control subjects, completely failed to adapt their investments when interacting with a trustworthy and an untrustworthy partner. In the non-social task, BLA-damaged subjects learned from positive outcomes but differed from the controls by not learning from negative outcomes. Our data extend findings in rodent research by showing that the human BLA is essential for social experiential learning and provide confirmatory evidence of divergent mechanisms for differentially valenced outcomes in non-social learning.
Subject(s)
Basolateral Nuclear Complex/physiology , Social Learning/physiology , Trust , Adult , Female , Humans , Middle Aged , Problem-Based LearningABSTRACT
Psychopathic offenders have a high propensity to violate social norms, as indicated for instance by their widespread lying and cheating behaviour. The reasons for their norm violations are not well understood, though, as they are able to recognise norms in a given situation and also punish norm violators. In this study, we investigated whether psychopathic offenders would violate fairness norms during a repeated trust game because of increased profit-maximising concerns. We measured back-transfer decisions in the repeated trust game, and affective arousal by means of skin conductance responses (SCR) in violent offenders with varying degrees of psychopathy, and non-offenders with low-trait psychopathy. Psychopathy in offenders was measured with the Psychopathy Checklist-Revised (PCL-R). In the task, a participant and an interaction partner entrusted each other money for multiple rounds with the goal to earn as much money as possible. Fairness norm violations were positively associated with Factor 2 scores (the lifestyle/anti-social psychopathy subscale) of the PCL-R, but this was not accompanied by clear profit-maximising behaviour. In addition, anticipatory arousal to self-advantageous decisions was higher in all offenders, independent of their degree of psychopathy, compared with non-offenders. The results of our study widen our understanding of social decision-making in psychopathy. They also suggest treatment possibilities in offenders scoring high on Factor 2, targeting empathic concern and related prosocial intentions to overcome norm-violating behaviour.
Subject(s)
Antisocial Personality Disorder/physiopathology , Antisocial Personality Disorder/psychology , Social Behavior , Social Norms , Trust/psychology , Action Potentials , Adult , Criminals , Galvanic Skin Response , Games, Experimental , Humans , Interpersonal Relations , Male , RewardABSTRACT
Aims: Chronic cocaine users display impaired social cognitive abilities, reduced prosocial behavior, and pronounced cluster B personality disorder (PD) symptoms all contributing to their social dysfunctions in daily life. These social dysfunctions have been proposed as a major factor for maintenance and relapse of stimulant use disorders in general. However, little is known about the reversibility of social cognitive deficits and socially problematic personality facets when stimulant use is reduced or ceased. Therefore, we examined the relation between changing intensity of cocaine use and the development of sociocognitive functioning and cluster B PD symptomatology over the course of 1 year. Methods: Social cognition, social decision-making, and cluster B PD symptoms were assessed in 38 cocaine users (19 with increased and 19 with decreased use) and 48 stimulant-naive healthy controls at baseline and at 1-year follow-up. Cocaine use severity was objectively determined by quantitative 6-month hair analyses. The categorization of the two cocaine user groups was based on a combination of absolute (± 0.5 ng/mg) and relative (± 10%) changes in the cocaine hair concentration between baseline and the 1-year follow-up. Social cognition was assessed using the Multifaceted Empathy Test (MET) and the Movie for the Assessment of Social Cognition (MASC). A combined Distribution/Dictator Game was applied for assessing social decision-making. Cluster B PD symptoms were measured by a Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II) PD questionnaire according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). Results: Increased cocaine use was linked to worsened empathy, while decreased cocaine use went along with improved emotional empathy. Moreover, whereas decreased cocaine use was associated with reduced severity of self-reported cluster B PD symptoms, these symptoms remained largely stable in increasers. In contrast to a significant reduction of prosocial behavior at baseline in the combined cocaine user group, specifically decreasers were not statistically distinguishable from controls at the follow-up. Conclusions: Sociocognitive deficits and cluster B PD symptoms of chronic cocaine users are adaptable over time as they covary with the increase or decrease in cocaine use. Hence, abstinence orientation and training of social cognition and interaction might improve social functioning, and should therefore be important therapeutic elements in cocaine addiction treatment.
ABSTRACT
Field studies have demonstrated that humans become more generous, helpful and compliant after having been touched by another person. Here, we explored whether these effects are larger for touch activating the C-tactile (CT) fibres, as it is ascribed a particular role in establishing and maintaining bonds and affiliative interactions. The role of CT-targeted and non-targeted touch on prosocial behaviour was investigated in three different experiments using a trust game and a task measuring individual differences in social value orientations (the SVO task). Whereas participants in general acted prosocially, there was no influence of CT-targeted touch on prosocial behaviour, both in comparison to non-CT-targeted control touch and visual (non-tactile) stimulation. The null findings were further corroborated by Bayesian statistics. Thus, under the controlled laboratory conditions employed, CT-targeted touch did not play a particular role in prosocial behaviour. This indicates that touch does not increase prosocial behaviour in the absence of meaningful social and psychological connotations. Any touch related effects on prosocial behaviour likely depends on the ecological validity of the situation.
ABSTRACT
Testosterone has been implicated in the regulation of emotional responses and risky decision-making. However, the causal effect of testosterone upon emotional decision-making, especially in non-social settings, is still unclear. The present study investigated the role of testosterone in counterfactual thinking: regret is an intense negative emotion that arises from comparison of an obtained outcome from a decision against a better, non-obtained (i.e. counterfactual) alternative. Healthy male participants (nâ¯=â¯64) received a single-dose of 150â¯mg testosterone Androgel in a double-blind, placebo-controlled, between-participants design. At 180â¯min post-administration, participants performed the counterfactual thinking task. We applied a computational model derived from behavioral economic principles to uncover latent decision-making mechanisms that may be invisible in simple choice analyses. Our data showed that testosterone increased the ability to use anticipated regret to guide choice behavior, while reducing choice based on expected value. On affective ratings, testosterone increased sensitivity to both obtained and counterfactual outcomes. These findings provide evidence that testosterone causally modulates emotional decision-making, and highlight the role of testosterone in affective sensitivity.
Subject(s)
Decision Making/drug effects , Emotions/drug effects , Testosterone/administration & dosage , Adult , Choice Behavior/drug effects , Choice Behavior/physiology , Decision Making/physiology , Double-Blind Method , Emotions/physiology , Gambling , Healthy Volunteers , Humans , Male , RewardABSTRACT
BACKGROUND: In women, low sexual desire and/or sexual arousal can lead to sexual dissatisfaction and emotional distress, collectively defined as female sexual interest/arousal disorder (FSIAD). Few pharmaceutical treatment options are currently available. AIM: To investigate the efficacy and safety of 2 novel on-demand pharmacologic treatments that have been designed to treat 2 FSIAD subgroups (women with low sensitivity for sexual cues and women with dysfunctional over-activation of sexual inhibition) using a personalized medicine approach using an allocation formula based on genetic, hormonal, and psychological variables developed to predict drug efficacy in the subgroups. METHODS: 497 women (21-70 years old) with FSIAD were randomized to 1 of 12 8-week treatment regimens in 3 double-blinded, randomized, placebo-controlled, dose-finding studies conducted at 16 research sites in the United States. Efficacy and safety of the following on-demand treatments was tested: placebo, testosterone (T; 0.5 mg), sildenafil (S; 50 mg), buspirone (B; 10 mg) and combination therapies (T 0.25 mg + S 25 mg, T 0.25 mg + S 50 mg, T 0.5 mg + S 25 mg, T 0.5 mg + S 50 mg, and T 0.25 mg + B 5 mg, T 0.25 mg + B 10 mg, T 0.5 mg + B 5 mg, T 0.5 mg + B 10 mg). OUTCOMES: The primary efficacy measure was the change in satisfying sexual events (SSEs) from the 4-week baseline to the 4-week average of the 8-week active treatment period after medication intake. For the primary end points, the combination treatments were compared with placebo and the respective monotherapies on this measure. RESULTS: In women with low sensitivity for sexual cues, 0.5 mg T + 50 mg S increased the number of SSEs from baseline compared with placebo (difference in change [Δ] = 1.70, 95% CI = 0.57-2.84, P = .004) and monotherapies (S: Δ = 1.95, 95% CI = 0.44-3.45, P = .012; T: Δ = 1.69, 95% CI = 0.58-2.80, P = .003). In women with overactive inhibition, 0.5 mg T + 10 mg B increased the number of SSEs from baseline compared with placebo (Δ = 0.99, 95% CI = 0.17-1.82, P = .019) and monotherapies (B: Δ = 1.52, 95% CI = 0.57-2.46, P = .002; T: Δ = 0.98, 95% CI = 0.17-1.78, P = .018). Secondary end points followed this pattern of results. The most common drug-related side effects were flushing (T + S treatment, 3%; T + B treatment, 2%), headache (placebo treatment, 2%; T + S treatment, 9%), dizziness (T + B treatment, 3%), and nausea (T + S treatment, 3%; T + B treatment, 2%). CLINICAL IMPLICATIONS: T + S and T + B are promising treatments for women with FSIAD. STRENGTHS AND LIMITATIONS: The data were collected in 3 well-designed randomized clinical trials that tested multiple doses in a substantial number of women. The influence of T + S and T + B on distress and the potentially sustained improvements after medication cessation were not investigated. CONCLUSIONS: T + S and T + B are well tolerated and safe and significantly increase the number of SSEs in different FSIAD subgroups. Tuiten A, van Rooij K, Bloemers J, et al. Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials. J Sex Med 2018;15:201-216.
Subject(s)
Buspirone/administration & dosage , Sexual Dysfunctions, Psychological/drug therapy , Sildenafil Citrate/administration & dosage , Testosterone/administration & dosage , Adult , Aged , Arousal/drug effects , Cues , Double-Blind Method , Female , Humans , Inhibition, Psychological , Libido/drug effects , Middle Aged , Randomized Controlled Trials as Topic , Sexual Behavior/drug effects , Sexual Dysfunctions, Psychological/psychology , Sildenafil Citrate/pharmacology , Testosterone/therapeutic use , Young AdultABSTRACT
Testosterone has been linked to social status seeking in humans. The present study investigated the effects of testosterone administration on implicit and explicit preferences for status goods in healthy male participants (n = 64), using a double-blind, placebo-controlled, between-subjects design. We also investigated the interactive effect between second-to-fourth digit ratio (2D:4D; i.e., a proximal index of prenatal testosterone) and testosterone treatment on status preferences. Results showed that testosterone administration has no discernable influence on self-reported willingness-to-pay (i.e., the explicit measure) or implicit attitudes towards status goods. Individuals with lower 2D:4D (i.e., more masculine) had more positive attitudes for high-status goods on an Implicit Association Task, and this association was abolished with testosterone administration. These data suggest interactive effects of acute testosterone administration and prenatal testosterone exposure on human social status seeking, and highlight the utility of implicit methods for measuring status-related behavior.