Androstadienone modulates human aggression in a sex-dependent manner.

Chemosensory communication is ubiquitous in human social interaction. Androstadienone is a potential candidate human sex pheromone that is associated with social dominance and competition. The aim of the present study was to investigate the effects of androstadienone on aggression. We specifically distinguished two types of aggression, namely proactive and reactive aggression. Two hundred and six male and female participants received either androstadienone or a control carrier in a double-blind, placebo-controlled, between-participants design. Participants performed two aggression tasks, one on reactive aggression and the other on proactive aggression, while they were exposed to the olfactory stimuli. The results revealed that for men, smelling androstadienone reduced both reactive and proactive aggression, whereas it increased reactive aggression in women. These effects were present despite the olfactory stimuli not being explicitly discriminable. These findings provide direct evidence that androstadienone modulates human aggression in a sex-dependent manner.

Enhancing attraction of the vector mosquito Aedes albopictus by using a novel synthetic odorant blend.

BACKGROUND: The Asian tiger mosquito, Aedes albopictus, an increasingly relevant arboviral vector, has spread worldwide. However, currently available tools are limited in terms of effective monitoring of vector populations and accurate determination of the extent of viral transmission, especially before and during outbreaks. Therefore, it is essential to develop novel monitoring and surveillance tools, particularly those that target adult mosquitoes and enhance the trapping efficiency for Ae. albopictus. METHODS: A variety of human body odorants associated with different types of mosquito olfactory receptors were selected, and their attractiveness to Ae. albopictus was tested by a four-arm olfactometer. The optimal compatibility and proportion of the odorants, Mix-5, was observed via orthogonal design analyses. The attractiveness of Mix-5 to Ae. albopictus in the laboratory was assessed using Mosq-ovitraps and Electric Mosquito Killers. In the field, the effectiveness of generic BG-Lure, Mix-5 and a control treatment was compared with a baited Biogents Sentinel trap (BGS-trap) using a Latin square design. RESULTS: In the olfactometer experiments, the attractiveness of the selected candidate compounds at varying dilutions was poor when the individual compounds were used alone. The optimal combination, Mix-5, was generated based on orthogonal design analyses. In the laboratory, the average numbers of female Ae. albopictus mosquitoes attracted by the synthetic odorant blend Mix-5 were 27.00 and 27.50, compared with 12.00 and 14.83 for the control, when using Mosq-ovitraps and Electric Mosquito Killers, respectively. In the field, the average number of Ae. albopictus female mosquitoes trapped by Mix-5 was 9.67 females/trap, whereas the average numbers for BG-Lure and the control were 7.78 and 4.47, respectively. The lure also played an important role in attracting Culex quinquefasciatus mosquitoes, and the average numbers of Cx. quinquefasciatus female mosquitoes attracted by Mix-5, BG-Lure and the control were 18.78, 25.11 and 12.22, respectively. CONCLUSIONS: A human odor-based bait blend was developed and exhibited enhanced effectiveness at attracting Ae. albopictus This blend can be used to monitor and trap dengue vector mosquitoes in Chinese cities.

Influence of the Male Axillary Extracts on Regulation of Menstrual Cycles in Women.

The effect of male axillary extract on the length and regularity of the menstrual cycle in women was studied in a long-term experiment (9 months). The male secret extract had no statistically significant influence on the menstrual cycle duration in the reproductive-age women (21-45 years) with normal (26-32 days) and regular cycles or in women with abnormally short (<26 days) cycles. In the group of the reproductive-age women with irregular and abnormally long (>32 days) cycles, as well as in the group of the premenopauseage women (46-51 years) with irregular cycles, the secret extract caused a significant shortening of the menstrual cycle as compared to the control. The effect was preserved for at least two months after the exposure completed.

The human body odor compound androstadienone leads to anger-dependent effects in an emotional Stroop but not dot-probe task using human faces.

The androgen derivative androstadienone is a substance found in human sweat and thus is a putative human chemosignal. Androstadienone has been studied with respect to effects on mood states, attractiveness ratings, physiological and neural activation. With the current experiment, we aimed to explore in which way androstadienone affects attention to social cues (human faces). Moreover, we wanted to test whether effects depend on specific emotions, the participants' sex and individual sensitivity to smell androstadienone. To do so, we investigated 56 healthy individuals (thereof 29 females taking oral contraceptives) with two attention tasks on two consecutive days (once under androstadienone, once under placebo exposure in pseudorandomized order). With an emotional dot-probe task we measured visuo-spatial cueing while an emotional Stroop task allowed us to investigate interference control. Our results suggest that androstadienone acts in a sex, task and emotion-specific manner as a reduction in interference processes in the emotional Stroop task was only apparent for angry faces in men under androstadienone exposure. More specifically, men showed a smaller difference in reaction times for congruent compared to incongruent trials. At the same time also women were slightly affected by smelling androstadienone as they classified angry faces more often correctly under androstadienone. For the emotional dot-probe task no modulation by androstadienone was observed. Furthermore, in both attention paradigms individual sensitivity to androstadienone was neither correlated with reaction times nor error rates in men and women. To conclude, exposure to androstadienone seems to potentiate the relevance of angry faces in both men and women in connection with interference control, while processes of visuo-spatial cueing remain unaffected.

A human chemosignal modulates frontolimbic activity and connectivity in response to emotional stimuli.

Evidence suggests the putative human pheromone Δ4,16-androstadien-3-one (androstadienone), a natural component of human sweat, increases attention to emotional information when passively inhaled, even in minute amounts. However, the neural mechanisms underlying androstadienone's impact on the perception of emotional stimuli have not been clarified. To characterize how the compound modifies neural circuitry while attending to emotional information, 22 subjects (11 women) underwent two fMRI scanning sessions, one with an androstadienone solution and one with a carrier control solution alone on their upper lip. During each session, participants viewed blocks of emotionally positive, negative, or neutral images. The BOLD response to emotional images (relative to neutral images) was greater during exposure to androstadienone in right orbitofrontal and lateral prefrontal cortex, particularly during positive image blocks. Androstadienone did not impact the response to social images, compared to nonsocial images, and results were not related to participant sex or olfactory sensitivity. To examine how androstadienone influences effective connectivity of this network, a dynamic causal model was employed with primary visual cortex (V1), amygdala, prefrontal cortex, and orbitofrontal cortex on each side. These models indicated that emotional images increased the drive from V1 to the amygdala during the control session. With androstadienone present, this drive to amygdala was decreased specifically for positive images, which drove downstream increases in orbitofrontal and prefrontal activity. This evidence suggests that androstadienone may act as a chemical signal to increase attention to positively valenced information via modifications to amygdala connectivity.

Chemosensory anxiety cues enhance the perception of fearful faces - An fMRI study.

Recent evidence suggests that humans can communicate emotion via chemosensory signals. Olfactory cues signaling anxiety can bias the perception of ambiguous stimuli, but the underlying neurobiological mechanisms of this effect are currently unknown. Here, we investigated the brain responses to subtle changes in facial expressions in response to anxiety chemosensory cues. Ten healthy individuals donated their sweat in two situations: while anticipating an important oral examination (anxiety condition) and during physical exercise (control condition). Subsequently, 24 participants completed a parametrically morphed (neutral to fearful) emotion recognition task under exposure to the olfactory cues of anxiety and sports, in the fMRI scanner. Behaviorally, the participants rated more discernible fearful faces as more fearful and neutral faces as more neutral under exposure to the anxiety cues. For brain response, under exposure to the anxiety cues, increased fearfulness of the face corresponded to increased activity in the left insula and the left middle occipital gyrus extending into fusiform gyrus. Moreover, with higher subjective ratings of facial fearfulness, participants additionally showed increased activity in the left hippocampus. These results suggest that chemosensory anxiety cues facilitate processing of socially relevant fearful stimuli and boost memory retrieval due to enhanced emotional context.

Swelling of Erectile Nasal Tissue Induced by Human Sexual Pheromone.

Most chemically mediated sexual communication in humans remains uncharacterized. Yet the study of sexual communication is decisive for understanding sexual behavior and evolutive mechanisms in our species. Here we provide the evidence to consider 4,16-androstadien-3-one (AND) as a man's sexual pheromone. Our experiment provides support for the physiological effect of AND on nasal airway resistance (Rna) in women, as assessed by anterior rhinomanometry. We found that AND administration increased the area of turbinate during the ovulatory phase, resulting in an increase of Rna. Thus, we discovered that minute amounts of AND, acting through neuroendocrine brain control, regulate Rna and consequently affect the sexual physiology and behavior. Fascinatingly, this finding provides the evidence of the preservation of chemosexual communication in humans, which it has been largely neglected due to its unconscious perception and concealed nature. Therefore, chemical communication is a plesiomorphic evolutive phenomenon in humans.

The smelling of Hedione results in sex-differentiated human brain activity.

A large family of vomeronasal receptors recognizes pheromone cues in many animals including most amphibia, reptiles, rhodents, and other mammals. Humans possess five vomeronasal-type 1 receptor genes (VN1R1-VN1R5), which code for proteins that are functional in recombinant expression systems. We used two different recombinant expression systems and identified Hedione as a ligand for the putative human pheromone receptor VN1R1 expressed in the human olfactory mucosa. Following the ligand identification, we employed functional magnetic resonance imaging (fMRI) in healthy volunteers to characterize the in vivo action of the VN1R1 ligand Hedione. In comparison to a common floral odor (phenylethyl alcohol), Hedione exhibited significantly enhanced activation in limbic areas (amygdala, hippocampus) and elicited a sex-differentiated response in a hypothalamic region that is associated with hormonal release. Utilizing a novel combination of methods, our results indicate that the putative human pheromone receptor VN1R1 is involved in extra-olfactory neuronal activations induced by the odorous substance Hedione. The activation of VN1R1 might play a role in gender-specific modulation of hormonal secretion in humans.

Identification of human semiochemicals attractive to the major vectors of onchocerciasis.

BACKGROUND: Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of traps that have the potential for replacing humans for surveillance of O. volvulus in the vector population. However, the key chemical components of human odor that are attractive to vector black flies have not been identified. METHODOLOGY/PRINCIPAL FINDINGS: Human sweat compounds were analyzed using GC-MS analysis and compounds common to three individuals identified. These common compounds, with others previously identified as attractive to other hematophagous arthropods were evaluated for their ability to stimulate and attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato) and Latin America (Simulium ochraceum s. l.) using electroantennography and a Y tube binary choice assay. Medium chain length carboxylic acids and aldehydes were neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by short chain aliphatic alcohols and aldehydes. Both species were attracted to ammonium bicarbonate and acetophenone. The compounds were shown to be attractive to the relevant vector species in field studies, when incorporated into a formulation that permitted a continuous release of the compound over time and used in concert with previously developed trap platforms. CONCLUSIONS/SIGNIFICANCE: The identification of compounds attractive to the major vectors of O. volvulus will permit the development of optimized traps. Such traps may replace the use of human vector collectors for monitoring the effectiveness of onchocerciasis elimination programs and could find use as a contributing component in an integrated vector control/drug program aimed at eliminating river blindness in Africa.

A putative human pheromone, androstadienone, increases cooperation between men.

Androstadienone, a component of male sweat, has been suggested to function as a human pheromone, an airborne chemical signal causing specific responses in conspecifics. In earlier studies androstadienone has been reported to increase attraction, affect subjects' mood, cortisol levels and activate brain areas linked to social cognition, among other effects. However, the existing psychological evidence is still relatively scarce, especially regarding androstadienone's effects on male behaviour. The purpose of this study was to look for possible behavioural effects in male subjects by combining two previously distinct branches of research: human pheromone research and behavioural game theory of experimental economics. Forty male subjects participated in a mixed-model, double-blind, placebo-controlled experiment. The participants were exposed to either androstadienone or a control stimulus, and participated in ultimatum and dictator games, decision making tasks commonly used to measure cooperation and generosity quantitatively. Furthermore, we measured participants' salivary cortisol and testosterone levels during the experiment. Salivary testosterone levels were found to positively correlate with cooperative behaviour. After controlling for the effects of participants' baseline testosterone levels, androstadienone was found to increase cooperative behaviour in the decision making tasks. To our knowledge, this is the first study to show that androstadienone directly affects behaviour in human males.

Differential processing of social chemosignals obtained from potential partners in regards to gender and sexual orientation.

On an individual level, human body odors carry information about whether a person is an eligible mate. The current studies investigate if body odors also transmit information about individuals being potential partners in more general terms, namely in regards to gender and sexual orientation. In study 1, 14 gay and 14 heterosexual men were presented with body odors obtained from potential partners (gay male and heterosexual female body odors, respectively) and heterosexual male body odor as a control. In study 2, 14 lesbian and 14 heterosexual women were presented with lesbian female and heterosexual male body odors representing body odors of potential partners, and heterosexual female body odor as a control. Central nervous processing was analyzed using chemosensory event-related potentials and current source density analysis (64-channel EEG recording). Gay and heterosexual men responded with shorter P2 latencies to the body odors of their preferred sexual partners, and lesbian women responded with shorter P2 latencies to body odors of their preferred gender. In response to heterosexual male body odors, lesbian women displayed the most pronounced P3 amplitude, and distinct neuronal activation in medial frontal and parietal neocortical areas. A similar pattern of neuronal activation was observed in gay men when presented with heterosexual male body odor. Both the early processing advantage (P2) for desirable partners' body odors as well as the enhanced evaluative processing (P3, CSD) of undesirable partners' body odors suggest that human body odors indeed carry information about individuals being potential partners in terms of gender and sexual orientation.

Is androstadienone a putative human pheromone?

On the basis of different evidences, androstadienone, a steroid compound produced in the armpit, has been proposed as a human pheromone, although its physiological levels appear too low to induce a response under experimental conditions. For this reason, the majority of researchers in this area puts into question the "legitimacy" of androstadienone, and prefers to consider the axillary extracts in its entirety, like a sort of "medicinal tea", the components of which still remain to be identified, but that taken together may induce a response, or function as a carrier of other active substances. Another option is that androstadienone acts with varying degrees of potency and, at lower concentrations, according to the context and to specific behavioral situations. The aim of this paper is to review all relevant data regarding androstadienone, in order to ascertain whether it may be considered a physiological pheromone and, as such, a possible target of future modulators of some human behaviors.

Using nylon strips to dispense mosquito attractants for sampling the malaria vector Anopheles gambiae s.s.

Synthetic versions of human derived kairomones can be used as baits when trapping host seeking mosquitoes. The effectiveness of these lures depends not only on their attractiveness to the mosquitoes but also on the medium from which they are dispensed. We report on the development and evaluation of nylon strips as a method of dispensing odorants attractive to the malaria vector, Anopheles gambiae s.s. (Giles). When a synthetic blend of attractants was dispensed using this method, significantly more mosquitoes were trapped than when two previous methods, open glass vials or low density polyethylene sachets were used. We conclude that the nylon strips are suitable for dispensing odorants in mosquito trapping operations and can be adopted for use in rural and remote areas. The nylon material required is cheap and widely available and the strips can be prepared without specialized equipment or electricity.

Acute olfactory response of Culex mosquitoes to a human- and bird-derived attractant.

West Nile virus, which is transmitted by Culex mosquitoes while feeding on birds and humans, has emerged as the dominant vector borne disease in North America. We have identified natural compounds from humans and birds, which are detected with extreme sensitivity by olfactory receptor neurons (ORNs) on the antennae of Culex pipiens quinquefasciatus (Cx. quinquefasciatus). One of these semiochemicals, nonanal, dominates the odorant spectrum of pigeons, chickens, and humans from various ethnic backgrounds. We determined the specificity and sensitivity of all ORN types housed in different sensilla types on Cx. quinquefasciatus antennae. Here, we present a comprehensive map of all antennal ORNs coding natural ligands and their dose-response functions. Nonanal is detected by a large array of sensilla and is by far the most potent stimulus; thus, supporting the assumption that Cx. quinquefasciatus can smell humans and birds. Nonanal and CO(2) synergize, thus, leading to significantly higher catches of Culex mosquitoes in traps baited with binary than in those with individual lures.

Pheromone signal transduction in humans: what can be learned from olfactory loss.

Because humans seem to lack neuronal elements in the vomeronasal organ (VNO), many scientists believe that humans are unable to detect pheromones. This view is challenged by the observations that pheromone-like compounds, 4,16-androstadien-3-one (AND) and oestra-1,3,5(10),16-tetraen-3-ol (EST), activate the human hypothalamus. Whether these activations are mediated via VNO, venous blood or olfactory mucosa is presently unknown. To disentangle between the three alternatives, we conducted activation studies in 12 heterosexual males with chronic anosmia because of nasal polyps. Polyposis hampers signal transduction via the olfactory mucosa without interfering with the VNO or the pheromone transport via venous blood. Twelve healthy men served as controls. Subjects were investigated with (15)O-H(2)O PET during smelling of odorless air (base line), AND, EST, vanillin, and acetone. Smelling of EST activated the anterior hypothalamus in controls, but not anosmics. Neither did the anosmics display cerebral activations with AND or vanillin. Clusters were detected only with the trigeminal odorant acetone, and only in the thalamus, brainstem, the anterior cingulate, and parts of the sensorimotor cortex. Direct comparisons with controls (controls-anosmics) showed clusters in the olfactory cortex (amygdala and piriform cortex) with AND, vanillin, and acetone, and in the anterior hypothalamus with EST. The observed absence of olfactory and presence of trigeminal activations in anosmics indicates that polyposis primarily affected signal processing via the olfactory mucosa. The anosmics inability to activate the hypothalamus with EST, therefore, suggests that in healthy men EST signals were primarily transmitted via the olfactory system.

Evidence that androstadienone, a putative human chemosignal, modulates women's attributions of men's attractiveness.

Considerable research effort has focused on whether specific compounds found within human body odor influence the behavior or physiology of other individuals. The most intensively studied is 4,16-androstadien-3-one, a chemical which is known to modulate mood and have activational effects in the sympathetic nervous system in a context-dependent manner, but whose action in mate-choice contexts remains largely untested. Here we present evidence that this androgen steroid may modulate women's judgments of men's attractiveness in an ecologically valid context. We tested the effects of androstadienone at a speed-dating event in which men and women interacted in a series of brief dyadic encounters. Men were rated more attractive when assessed by women who had been exposed to androstadienone, an effect that was seen in two out of three studies. The results suggest that androstadienone can influence women's attraction to men, and also that research into the modulatory effects of androstadienone should be made within ecologically valid contexts.

Smelling a single component of male sweat alters levels of cortisol in women.

Rodents use chemosignals to alter endocrine balance in conspecifics. Although responses to human sweat suggest a similar mechanism in humans, no particular component of human sweat capable of altering endocrine balance in conspecifics has yet been isolated and identified. Here, we measured salivary levels of the hormone cortisol in women after smelling pure androstadienone (4,16-androstadien-3-one), a molecule present in the sweat of men that has been suggested as a chemosignal in humans. We found that merely smelling androstadienone maintained significantly higher levels of the hormone cortisol in women. These results suggest that, like rodents, humans can influence the hormonal balance of conspecifics through chemosignals. Critically, this study identified a single component of sweat, androstadienone, as capable of exerting such influence. This result points to a potential role for synthetic human chemosignals in clinical applications.