Community Research and Development Information Service - CORDIS


SocioSmell Report Summary

Project ID: 670798
Funded under: H2020-EU.1.1.

Periodic Reporting for period 1 - SocioSmell (Social Chemosignaling as a Factor in Human Behavior in both Health and Disease)

Reporting period: 2015-09-01 to 2017-02-28

Summary of the context and overall objectives of the project

"The issue being addressed
We humans trust our nose over our eyes and ears in two of the most critical decisions we make: what we eat, and with whom we mate. Our reliance on our nose for key survival-related decisions such as eating and mating is subserved by an astonishingly keen olfactory system. We have in our nose ~6 million olfactory receptors, that as far as we know, are not different in their design and function from those of a rat or a dog. These receptors feed into olfactory bulbs that are, in proportion to the rest of our brain, much smaller than those of rodents, but in absolute terms, bigger than even the entire brain of some rodents. These bulbs then convey information to a human cortical olfactory and limbic system that is fully intact. Indeed, using this system, humans can detect odorants at parts-per-trillion dilution, they can discriminate between a huge number of molecules that differ by the smallest of molecular perturbations, and they can learn to achieve olfactory feats as unlikely as scent-tracking. One of the major uses of olfaction by macrosmatic mammals is in chemical communication. Mammals emit bodily-sourced odorants through urine and other secretions, and these odorants signal meaningful information to conspecifics. Some mammalian chemosignals induce effects that are nothing less than dramatic. For example, the Bruce effect describes the phenomena whereby a pregnant rodent will miscarry if exposed to the odorant of a non-fathering male within a critical early stage of pregnancy. It is hard to imagine a decision with greater evolutionary cost than a voluntary miscarriage, and this ""decision"" is made based on a chemosignal.

With the above in mind, the major objective of this proposal is to test the hypothesis that like all mammals, humans constantly exchange chemosignals that influence brain activity, hormonal state, and behavior.

Importance for society
Understanding the mechanisms of human chemosignaling will provide a better understanding of the link between brain and behavior, and may uncover specific chemosignaling molecules with important pharmacological implications.

Overall objectives
In Aim 1 we will ask what else do human social chemosignals signal? We will test the novel hypotheses that human social chemosignals communicate social status (dominance/submissiveness).

In Aim 2 we will ask how do humans exchange social chemosignals? We will test the novel hypotheses that handshaking is a chemosignaling mechanism, and that humans constantly chemo-investigate each other.

In Aim 3 we will ask what are the brain mechanisms that subserve human social chemosignaling? We will test the hypothesis that human social chemosignaling is independent of the main olfactory system.

In Aim 4 we will ask what happens when human social chemosignaling goes wrong? We will test the novel hypothesis that altered chemosignaling is a component of autism spectrum disorder.

Taken together, the answers to these questions promise to provide a novel framework for understanding human behavior in both health and disease."

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

This project is running full-steam, mostly on or ahead of schedule. This is plainly evident in the publication record: We completed the study of human hand-shaking behaviour, finding that humans indeed sniff their own hands to obtain chemosignaling information. We published these results in a manuscript in the journal eLife (Frumin et al.). We completed the effort with children with autism, finding that sniffing behaviour is profoundly altered in autism. We published these results in a manuscript in the journal Current Biology (Rozenkrantz et al.). We also developed a novel method for characterizing individual olfactory perception, and published this in the journal PNAS (Secundo et al.). In other words, this project already gave rise to three high-profile publications. In addition, we have made significant progress on additional fronts, and have two additional project publications in review (both in high-profile journals). Thus, the project is ploughing ahead full-steam, and we have no delays or problems to report.


A Social Chemosignaling Function for Human Handshaking
Social chemosignaling is a part of human behavior, but how chemosignals transfer from one individual to another is unknown. In turn, humans greet each other with handshakes, but the functional antecedents of this behavior remain unclear. To ask whether handshakes are used to sample conspecific social chemosignals we covertly filmed 271 subjects within a structured greeting event either with or without a handshake. We found that humans often sniff their own hands, and selectively increase this behavior after handshake. After handshakes within gender, subjects increased sniffing of their own right shaking hand by more than 100% (Figure 1). In contrast, after handshakes across gender, subjects increased sniffing of their own left non-shaking hand by more than 100%. Tainting participants with unnoticed odors significantly altered the effects, thus verifying their olfactory nature. Thus, handshaking may functionally serve active yet subliminal social chemosignaling, which likely plays a large role in ongoing human behavior.

A Mechanistic Link Between Olfaction and Autism Spectrum Disorder
Internal action models (IAMs) are brain templates for sensory-motor coordination underlying diverse behaviors. An emerging theory suggests that impaired IAMs are a common theme in autism spectrum disorder (ASD). However, whether impaired IAMs occur across sensory systems, and how they relate to the major phenotype of ASD, namely impaired social communication, remains unclear. Olfaction relies on an IAM known as the sniff-response, where sniff magnitude is automatically modulated to account for odor valence. To test the failed-IAM theory in olfaction we precisely measured the non-verbal non-task-dependent sniff-response concurrent with pleasant and unpleasant odors in 36 children; 18 with ASD and 18 matched typically developing (TD) controls. We found that whereas TD children generated a typical adult-like sniff-response within 305 milliseconds of odor onset, ASD children had a profoundly altered sniff-response, sniffing equally regardless of odor valance Figure 2). This difference persisted despite equal reported odor perception and allowed for 81% correct ASD classification based on the sniff-response alone (binomial, p < 0.001). Moreover, increasingly aberrant sniffing was associated with increasingly severe ASD (r = -0.75, p < 0.001), specifically with social (r = -0.72, p < 0.001) but not motor (r < -0.38, p > 0.18) impairment. These results uncover a novel ASD marker implying a mechanistic link between the underpinnings of olfaction and ASD, and directly linking an impaired IAM with impaired social abilities.

Olfactory Fingerprints: Individual Olfactory Perception Reveals Meaningful Non-Olfactory Genetic Information
Cyrano de Bergerac observed that: “a large nose is the mark of a witty, courteous, affable, generous and liberal man”. Here we report that individual noses, not how they look but rather how they function, indeed say a lot about a person.
Each person expresses a potentially unique subset of ~400 different olfactory receptor subtypes. Given that the receptors we express partially determine the odors we smell, it follows that each person may have a unique nose. To capture this, we devised a sensitive test of olfactory perception we termed the olfactory fingerprint. Olfactory fingerprints relied on matrices of perceived odorant similarity derived from descriptors applied to the odorants. We initially fingerprinted 89 individuals using 28 odors and 54 descriptors. We found that each person had a unique olfactory fingerprint (p < 10-10), which was odor specific but descriptor independent. We could identify individuals from this pool using randomly selected sets of seven odors and 11 descriptors alone. Extrapolating from this data, we determined that using 34 odors and 35 descriptors we could individually identify each of the seven billion people on earth (Figure 3). Olfactory perception, however, fluctuates over time, calling into question our proposed perceptual readout of presumably stable genetic makeup. To test whether fingerprints remain informative despite this temporal fluctuation, building on the linkage between olfactory receptors and human leukocyte antigen (HLA), we hypothesized that olfactory perception may predict HLA. We obtained olfactory fingerprints and HLA typing for 130 individuals, and found that olfactory fingerprint matching using only 4 odorants was significantly related to HLA matching (p < 10-4), such that olfactory fingerprints can save 32% of HLA tests in a population screen (p < 10-6). In conclusion, a precise measure of olfactory perception reveals meaningful non-olfactory genetic information.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The current achievements have two areas of potential societal impact:

1. Our olfactory marker for autism spectrum disorder (Rozenkrantz et al) may have diagnostic value. The marker we obtained is non-verbal non-task-dependent, and therefore may be obtained at a very early age. Following our publication, two groups have added this measure to their studies, and thus we expect a long-term follow-up that may provide for a novel diagnostic marker of autism that is applicable at a very early age.

2. Our individual olfactory profiles (Secundo et al) may provide meaningful information predictive on a host of fronts. In one study, we are investigating whether these fingerprints predict romantic fit. If they do, this can provide for a tool with potential societal and financial implications. In contrast, we are also examining whether olfactory fingerprints can provide an early indication for cognitive decline. If they do, they may prove valuable is diagnostics of neurodegenerative disease.

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