Amy R. Gordon

The Scent of Disease Human Body Odor Contains an Early Chemosensory Cue of Sickness

Observational studies have suggested that with time, some diseases result in a characteristic odor emanating from different sources on the body of a sick individual. Evolutionarily, however, it would be more advantageous if the innate immune response were detectable by healthy individuals as a first line of defense against infection by various pathogens, to optimize avoidance of contagion. We activated the innate immune system in healthy individuals by injecting them with endotoxin (lipopolysaccharide). Within just a few hours, endotoxin-exposed individuals had a more aversive body odor relative to when they were exposed to a placebo. Moreover, this effect was statistically mediated by the individuals’ level of immune activation. This chemosensory detection of the early innate immune response in humans represents the first experimental evidence that disease smells and supports the notion of a “behavioral immune response” that protects healthy individuals from sick ones by altering patterns of interpersonal contact.

The smell of age: perception and discrimination of body odors of different ages.

Our natural body odor goes through several stages of age-dependent changes in chemical composition as we grow older. Similar changes have been reported for several animal species and are thought to facilitate age discrimination of an individual based on body odors, alone. We sought to determine whether humans are able to discriminate between body odor of humans of different ages. Body odors were sampled from three distinct age groups: Young (20–30 years old), Middle-age (45–55), and Old-age (75–95) individuals. Perceptual ratings and age discrimination performance were assessed in 41 young participants. There were significant differences in ratings of both intensity and pleasantness, where body odors from the Old-age group were rated as less intense and less unpleasant than body odors originating from Young and Middle-age donors. Participants were able to discriminate between age categories, with body odor from Old-age donors mediating the effect also after removing variance explained by intensity differences. Similarly, participants were able to correctly assign age labels to body odors originating from Old-age donors but not to body odors originating from other age groups. This experiment suggests that, akin to other animals, humans are able to discriminate age based on body odor alone and that this effect is mediated mainly by body odors emitted by individuals of old age.

Aversive learning increases sensory detection sensitivity.

Increased sensitivity to specific cues in the environment is common in anxiety disorders. This increase in sensory processing can emerge through attention processes that enhance discrimination of a cue from other cues as well as through augmented senses that reduce the absolute intensity of sensory stimulation needed for detection. Whereas it has been established that aversive conditioning can enhance odor quality discrimination, it is not known whether it also changes the absolute threshold at which an odor can be detected. In two separate experiments, we paired one odor of an indistinguishable odor pair with an aversive outcome using a classical conditioning paradigm. Ability to discriminate and to detect the paired odor was assessed before and after conditioning. The results demonstrate that aversive conditioning increases absolute sensory sensitivity to a predictive odor cue in an odor-specific manner, rendering the conditioned odor detectable at a significantly lower (20%) absolute concentration. As animal research has found long-lasting change in behavior and neural signaling resulting from conditioning, absolute threshold was also tested eight weeks later. Detection threshold had returned to baseline level at the eight week follow-up session suggesting that the change in detection threshold was mediated by a transient reorganization. Taken together, we can for the first time demonstrate that increasing the biological salience of a stimulus augments the individuals absolute sensitivity in a stimulus-specific manner outside conscious awareness. These findings provide a unique framework for understanding sensory mechanisms in anxiety disorders as well as further our understanding of mechanisms underlying classical conditioning.

Individual Differences in the Chemical Senses: Is There a Common Sensitivity?

Taste, smell, and chemical irritation (so-called trigeminal sensation) combine in our daily experience to produce the supramodal sensation of flavor, are processed by partly overlapping neural mechanisms, and show functional interconnectivity in experiments. Given their collaboration in flavor formation and the well-established connections between these senses, it is plausible that polymodal detection mechanisms might contribute to individual differences in measured sensitivity. One would expect the existence of a general chemosensory sensitivity factor to result in associations among taste, smell, and trigeminal stimulation thresholds. Measures of 5 detection thresholds from all the chemical senses were assessed in the same group of young healthy subjects (n=57). An unbiased principal components analysis (PCA) yielded a 2-component solution. Component 1, on which taste thresholds loaded strongly, accounted for 29.4% of the total variance. Component 2, on which the odor and trigeminal lateralization thresholds loaded strongly, accounted for 26.9% of the total variance. A subsequent PCA restricted to a 3-component solution cleanly separated the 3 sensory modalities and accounted for 75% of the total variance. Thus, though there may be a common underlying factor that determines some individual differences in odor and trigeminal lateralization thresholds, a general chemical sensitivity that spans chemosensory modalities seems unlikely.

Brain Injury Alters Volatile Metabolome

Chemical signals arising from body secretions and excretions communicate information about health status as have been reported in a range of animal models of disease. A potential common pathway for diseases to alter chemical signals is via activation of immune function-which is known to be intimately involved in modulation of chemical signals in several species. Based on our prior findings that both immunization and inflammation alter volatile body odors, we hypothesized that injury accompanied by inflammation might correspondingly modify the volatile metabolome to create a signature endophenotype. In particular, we investigated alteration of the volatile metabolome as a result of traumatic brain injury. Here, we demonstrate that mice could be trained in a behavioral assay to discriminate mouse models subjected to lateral fluid percussion injury from appropriate surgical sham controls on the basis of volatile urinary metabolites. Chemical analyses of the urine samples similarly demonstrated that brain injury altered urine volatile profiles. Behavioral and chemical analyses further indicated that alteration of the volatile metabolome induced by brain injury and alteration resulting from lipopolysaccharide-associated inflammation were not synonymous. Monitoring of alterations in the volatile metabolome may be a useful tool for rapid brain trauma diagnosis and for monitoring recovery.

Processing of Human Body Odors

Human chemosensory signals are able to transmit a wide range of social information to conspecifics. Resulting from the interaction of several genetic and physiological processes (e. g., metabolic, immune, nervous), each individual produces a unique odor signature. The central processing of such chemosignals by conspecifics modifies physiological, behavioral, and psychological responses. To illuminate the importance of this mode of communication, we describe how humans produce, decode, and respond to warning chemosignals. Behavioral evidence highlighting the cognitive and emotional consequences of body odor communication will be discussed. Special attention will be devoted to the current understanding of human body odor neural processing. After an overview on the topic, we discuss the role that social chemosignals may have in our everyday life in health and disease.

Mind Over Age—Stereotype Activation and Olfactory Function

Given that context affects olfaction and the elderly exhibit olfactory deficits, the current study tested whether a subtle change in internal context, evoked by priming the elderly stereotype, would affect performance in a variety of olfactory tasks including odor sensitivity, discrimination, and identification (Experiment 1), as well as perceived odor intensity, pleasantness and familiarity, and an odor reaction time task (Experiment 2). Such internalization of the elderly stereotype has been demonstrated with slower walking speeds and fewer words recalled in a memory task. In the current study, 76 participants first listened to a presentation about age-related declines in olfaction and then participated in 3 language tasks which, unbeknownst to them, served as the elderly stereotype priming manipulation. This priming manipulation was effective at decreasing walking speed and word recall, confirming the findings of previous researchers; however, olfaction was not affected. Whether olfaction is resistant to stereotype priming is discussed.

Detection of Inflammation via Volatile Cues in Human Urine

Contagious disease is a major threat to survival, and the cost of relying on the immune system to defeat pathogens is high; therefore, behavioral avoidance of contagious individuals is arguably an adaptive strategy. Animal findings demonstrate the ability to detect and avoid sick individuals by the aid of olfactory cues, and a recent study indicated that human axillary odor also becomes more aversive as a function of immune activation. By injecting healthy human participants with lipopolysaccharide (0.6 ng/kg body weight) to experimentally induce inflammation, this study demonstrates that natural daily rhythms of urine odor-its perceived dimensions and volatile profile-are altered within hours of inflammation onset. Whereas healthy human urine decreases in averseness over the course of a single day, inflammation interrupts this process and results in an increased urine odor averseness and an altered volatile composition. These results support the notion that subtle and early cues of sickness may be detected and avoided, thereby complementing the immune system in its role of keeping us alive and healthy.