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Can scent-detection dogs detect the stress associated with trauma cue exposure in people with trauma

Resource Can scent-detection dogs detect the stress associated with trauma cue exposure in people with trauma 2024-03-30

Introduction: Post-traumatic stress disorder (PTSD) is an impairing mental health condition with high prevalence among military and general populations alike. PTSD service dogs are a complementary and alternative intervention needing scientific validation. We investigated whether dogs can detect putative stress-related volatile organic compounds (VOCs) in the breath of people with trauma histories (54% with PTSD) exposed to personalized trauma cues.

Methods: Breath samples were collected from 26 humans over 40 experimental sessions during a calm (control breath sample) and stressed state induced by trauma cue exposure (target breath sample). Two scent detection canines were presented with the samples in a two alternative forced choice (2AFC) discrimination and yes/no detection task. The 2AFC task assessed the dogs' ability to discriminate between the two states within the breath samples of one individual. The detection task determined their ability to generalize the target odour across different individuals and different stressful events of one individual. Signal Detection Theory was applied to assess dogs' sensitivity, specificity, precision, and response bias.

Results: The dogs performed at ∼90% accuracy across all sample sets in the discrimination experiment, and at 74% and 81% accuracy, respectively, in the detection experiment. Further analysis of dog olfactory performance in relation to human donor self-reported emotional responses to trauma cue exposure suggested the dogs may have been detecting distinct endocrine stress markers. One dog's performance correlated with the human donors' self-reported fear responses and the other dog's performance correlated with the human donors' self-reported shame responses. Based on these correlations between dog performance and donor self-report measures, we speculate that the VOCs each dog was detecting likely originated from the sympathetico-adreno-medullary axis (SAM; adrenaline, noradrenaline) in the case of the first dog and the hypothalamo-pituitary-adrenal axis (HPA; glucocorticoids) in the case of the second dog.

Conclusion: Our proof-of-concept study is the first to demonstrate that some dogs can detect putative VOCs emitted by people with trauma histories when experiencing distress theoretically associated with the intrusion and arousal/reactivity symptoms of PTSD. Results have potential to improve the effectiveness and training protocol of PTSD service dogs with a focus on enhancing their alert function.

1 Introduction

Post-traumatic stress disorder (PTSD) is a trauma- and stress-related disorder in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition [DSM-5; (1)] involving a persistent stress response to experiencing/witnessing a life-threatening or catastrophic event (2, 3) such as combat, sexual/physical assault, or disaster (1). PTSD symptoms fall into four clusters: intrusion/re-experiencing (e.g., flashbacks, nightmares), hyperarousal (e.g., hypervigilance, sleep perturbations), avoidance (avoiding trauma reminders), and cognition/mood symptoms (e.g., emotional numbing, negative emotions) (1, 2). PTSD is often comorbid with other psychiatric disorders (e.g., mood, anxiety, and substance use) (1, 2, 46) and physical health conditions (e.g., endocrinological, cardiovascular, and pain) (2, 7). Associated features include suicidal ideation (8) and impairments to family/relationships (9, 10), work (11, 12), well-being, and quality of life (13, 14).

PTSD is prevalent [7.8% lifetime prevalence in the U.S. general population (15), 9.2% in Canada (16)], particularly among veterans (17, 18) [up to 23%–30% (18, 19)]. Many more trauma-exposed individuals experience subthreshold PTSD symptoms. Developing effective treatments for full and subthreshold PTSD is paramount.

One complementary/alternative treatment for PTSD involves psychiatric service dogs–assistance dogs permanently placed with a patient and trained to help them (20). Trained tasks include alerting to early signs of intrusion/hyperarousal symptoms and interrupting/diffusing these episodes (2025). Growing evidence links service dogs use with clinically-significant long-term decreases in PTSD symptomatology, with the strongest effects for intrusion/hyperarousal symptoms (2026). PTSD service dogs are associated with increased quality of life and improved family and social functioning/integration (2224).

Interrupting or alerting to episodes of anxiety/distress (e.g., flashbacks, nightmares) is reported as within the top three most appreciated and frequently-used trained tasks by veterans with a PTSD service dog (24, 27). Most service dog providers consider dogs' ability to interrupt/alert to such episodes a task requiring training (3, 21, 24, 2830). Currently, PTSD service dogs are trained to respond to physical signs (e.g., fidgeting, fist-clenching) of upcoming intrusion/hyperarousal symptoms (e.g., flashbacks, anger) (3, 24, 28). We investigated whether dogs can detect the early onset of these episodes via the breath of people with trauma histories when exposed to trauma reminders. If reliance on olfactory cues is possible, service dogs might be trained to alert to upcoming intrusion/hyperarousal symptoms before physical signs manifest (31) and prior to patient awareness (7). Early distraction could remind patients to use skills learned in psychotherapy [e.g., mindfulness, relaxation (28)], increasing these skills' efficacy and preventing symptom escalation (30).

2 Background information

2.1 The basics of using scent-detection dogs in medicine

Canines' sense of smell is 10,000–100,000 times more sensitive than humans' (32). Research is investigating opportunities to apply dogs' acute olfaction to biomedical detection and alert tasks like detecting human cancers (3338), viruses [e.g., COVID-19; (39)], or parasites [e.g., malaria; (40)], and alerting to hypoglycemia (41), seizures (42), and dangerous bacteria (43, 44).
Three categories of individual human odours are: the stable "primary odour" based on the individual's genetics, age, and sex; the changing "secondary odour" based on endogenous dietary and environmental factors, including pathological status; and the "tertiary odour" based on exogenous factors like personal hygiene products (45, 46). These elements determine the individual scent profile of volatile organic compounds (VOCs) emanated from the human body (e.g., isoprene, monoterpenes) (45). As VOC molecules evaporate/sublimate, dogs can detect them from samples including breath, urine, and sweat (46, 47); greatest success has been achieved with breath (48).

Certain medical conditions alter the VOCs cells release into the respiratory system (41, 45), resulting in the condition's "signature scent" (48) or less specific olfactory biomarkers dogs could be trained to detect. Although it is unclear if every condition has its own VOC pattern, disease-specific profiles have been identified in several diseases/infections/metabolic changes in humans (e.g., cancers, cystic fibrosis, diabetes) (45, 47, 49, 50).

2.2 Evidence of the canine potential to detect human stress-related VOCs[

There is preliminary evidence of dogs' ability to detect VOCs associated with elevated human stress levels. One study (51) presented 31 pet dogs with salivary, interdigital, and perianal secretion samples from three dog donors and sweat samples from four human donors during one joyful, one neutral, and two stressful situations (i.e., a fear-inducing video and running for the humans). Regardless of donor species, dogs displayed higher cardiac activity and behavioural alertness and anxiety when sniffing samples collected during stressful vs. neutral/joyful situations (51).

Another study (52) collected sweat samples from eight humans after watching a fear- or joy-inducing video. Forty pet dogs displayed more stress-related behaviours and arousal (e.g., elevated heart rate) when sniffing pooled samples from the fear vs. joy or control (no human odour) conditions (52). A third study (53) collected breath and sweat samples from 36 humans immediately before and after a mental arithmetic task and validated their stress by blood pressure, heart rate, and self-report. The validated samples were then presented to four formerly-trained scent-detection dogs in a three alternative forced choice discrimination task (baseline and stress samples of the same donor, and a blank sample). Dogs were able to discriminate between stress and neutral samples by signalling the stress sample with an average accuracy of 93.75%.

The above-described studies suggest human stress responses involve VOCs that at least some dogs can detect, although the specific stress biomarker(s) dogs rely on remain unclear. Technological advancements have also successfully detected human stress response biomarkers in breath (54, 55) and a variety of bodily fluids [e.g., urine, blood, saliva (56)]. One pilot study (55) collected breath samples from 22 donors during a stress-inducing arithmetic test and a neutral (classical music) condition. Gas chromatography-mass spectrometry analysis detected six stress compounds with indole and 2-methyl-pentadecane the most discriminant. Their model demonstrated 83.3% sensitivity and 91.6% specificity (female donor samples), and 100% sensitivity and 90% specificity (male donor samples).

Another study (54) recruited 14 donors and subjected them to a stressful arithmetic task with a less and more intense version and a control condition (relaxing videos). Breath profiling by gas chromatography/ion mobility spectrometry revealed six stress-sensitive compounds with benzaldehyde common to the previously discussed study (55). The model demonstrated 78.5% sensitivity and 71.5% specificity (more intense stressor), and 61.5% sensitivity and 71.4% specificity (less intense stressor) (54). There is currently no technological sensor able to detect all stress biomarkers or simultaneously detect multiple biomarkers (regardless of VOC source) in a way allowing quick, reliable monitoring of an individual's stress levels (56).

Dogs might have an advantage as they likely possess a "sensor" capable of a more comprehensive and less specialised perception of the array of stress volatiles. There are several reasons why dogs could be sensitive to human stress VOCs. First, dogs might have developed olfactory recognition of human emotions during domestication (57). Alternatively, from an ethological viewpoint, it would be advantageous for predator species to be able to perceive volatiles indicating distress (and thus vulnerability/weakness) in prey (58).

Another possible mechanism is emotional contagion, which occurs when "another's emotional state triggers a similar emotional response in an observer" (59, p. 852). Indeed, dogs exhibit behaviours indicative of emotional contagion in response to visual behavioural signs of human distress (e.g., crying) (5961). Synchronisation is a broader term, defined as "doing the same thing, at the same time and at the same place, as others" (62, p. 181). Synchronisation has several adaptive values from cooperative defence against predators to raising offspring (62). Dogs have been shown to synchronise with their guardians when encountering unfamiliar objects/people [e.g., (63, 64)]. Synchronisation does not necessarily involve emotional contagion. Although studies of both emotional contagion and synchronisation thus far have involved dogs' responses to visual and audible behavioural cues in humans, certain VOCs may also contribute to eliciting these mechanisms in dogs.

2.3 The endocrinology of human stress response associated with PTSD

The main endocrinological factor characterising PTSD/anxiety disorders is chronic amygdalar and stress response over-activity (7, 65, 66). The amygdala is a part of the limbic system responsible for processing fear and other negative emotions, including both innate and conditioned aversive stimuli. Sensory information first reaches the amygdala that then activates the autonomic nervous system, after which the information is sent to the frontal/temporal lobes for further processing (7, 66). As amygdalar processing is often unconscious, informing the prefrontal cortex is not required before experiencing anxiety/fear. People may exhibit physiological stress/fear responses before being consciously aware of the stressor (7).

For PTSD, anxiety, and depression, there is an imbalance between amygdalar activity and prefrontal cortical activity–the amygdala is markedly over-active and the activation of the medial prefrontal cortex is to some extent impaired (2, 66). Without cortical processing, an aroused amygdala stimulates the sympathetic nervous system1, which proceeds to secrete stress-response hormones (7, 65). Two endocrine subsystems play a major role in re-establishing homeostasis in response to a stressor: the sympathetic-adreno-medullar (SAM) and the hypothalamic-pituitary-adrenal (HPA) axes. The SAM axis involves the catecholamines adrenaline and noradrenaline. The HPA axis involves the glucocorticoids cortisol and corticosterone (7, 65, 67).

The SAM axis reacts instantaneously: within milliseconds of an exposure to a stressor, the sympathetic nervous system engages the adrenal medulla to produce adrenaline and noradrenaline (7, 65, 67, 68). Reactions through the HPA axis unfold more slowly: the adrenal cortices start releasing glucocorticoids within minutes or hours from exposure (7, 65, 67). The endocrine sequence is also longer: the HPA axis requires the hypothalamus to signal the pituitary gland (via corticotropin releasing hormone) which must activate the adrenal cortex (via adrenocorticotropic hormone) (31).

The function of the SAM axis response is to prepare the organism for a sudden increase in energy demands, i.e., immediate fight-or-flight. Oxygen intake is increased by elevating respiration rate; heart rate is elevated; blood flow to the muscles and blood glucose levels are boosted to prepare for movement; processes not immediately necessary for survival (e.g., digestion, reproduction, growth) are inhibited; pain perception is blunted; and alertness and sensory/learning/memory functions are enhanced (7, 65, 67). The HPA axis reactions (glucocorticoids) support these processes in the long term. They are involved in mediating the stress reaction, recovering from it, and preparing for the next possible stressor(s) (7).

2.4 Goals and hypotheses

We investigated whether dogs could be trained to alert to the early onset of PTSD intrusion/hyperarousal symptoms by relying on olfactory cues. The goal was to determine whether dogs can detect and discriminate between breath samples of donors with a trauma exposure history and varying levels of PTSD symptoms, collected immediately before and during exposure to cues related to their personal traumatic experiences. This is the first study to investigate canine ability to detect stress volatiles theoretically involved in PTSD intrusion/hyperarousal symptoms.

We proposed three hypotheses. First, we hypothesised that at least some dogs can discriminate between breath samples collected from the same human donors during a personalised trauma cue vs. resting baseline. This requires that, when presented with the two samples, the canines can detect VOCs associated with stress-induced PTSD intrusion/arousal symptoms.

Second, we hypothesised that at least some dogs can detect the trauma cue breath samples across different individuals (or the same individual in different contexts) when presented with one sample (baseline or trauma cue) at a time. In real-life, dogs would not have simultaneous breath samples to compare but would be presented with one "sample". Confirmation of this second hypothesis would provide considerably stronger evidence for training PTSD alert dogs.

Finally, we hypothesised a positive correlation between dogs' performance and donors' self-reported negative affect during the trauma cue exposure (indices of human distress when confronting trauma reminders).
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