Volatile organic compound markers of psychological stress in skin: a pilot study

Abstract

The forehead was studied as a possible sampling site for capturing changes in volatile organic compound (VOC) profiles associated with psychological-stress. Skin-VOCs were sampled with a polydimethylsilicone (PDMS)-coupon and the resulting VOCs were recovered and analysed with two-stage thermal desorption gas chromatography-mass spectrometry.15 young adult volunteers (19 yr to 26 yr) participated in two interventions run in a randomised crossover design. One intervention, termed "Neutral", required the participants to listen to peaceful music, the other, termed a "paced audio serial addition task", required the participants to undertake a series of rapid mental arithmetic calculations in a challenging environment that induced a stress response. Skin-VOC samples were taken during each intervention. The resultant data were processed with dynamic background compensation, deconvolved, and registered to a common retention index scale.The importance of freezing skin patch samplers to -80 o C was determined during the method development phase of this study. The cumulative distribution function of the GC-MS data indicates the possibility that PDMS-coupons are selective towards the lower volatility VOC components in skin. The frequency distribution of the GC-MS data was observed to be approximately log-normal, and on the basis of this study, a further twoorders of magnitude reduction in sensitivity may be required before the complete skin-VOC profile may be characterised.Multi-variate analysis involving Pareto-scaling prior to partial least squares discriminant analysis identified four VOCs with the highest probability of contributing to the variance between the two states, and the responses to these VOCs were modelled with principle components analysis (PCA). Two VOCs, benzoic acid and n-decanoic acid were upregulated (14-and 8-fold respectively) and appear to be PASAT sensitive, with areas under (AUC) their receiver operator characteristic (ROC) curves of 0.813 and 0.852 respectively. A xylene isomer and 3-carene were down regulated 75 % and 97% respectively, and found to be predictive of the neutral intervention (ROC AUC values of 0.898 and 0.929 respectively). VOC profiles in skin appear to change with stress either due to increased elimination, elevated bacterial activity, or perhaps increased oxidative pathways.2

Identification of Suitable Biomarkers for Stress and Emotion Detection for Future Personal Affective Wearable Sensors

“…Two studies utilized different methodologies and found different stress biomarkers. The first study found changes in the concentrations of the biomarkers 2-hydroxy-1-phenylethanone, benzaldehyde, and 2-ethylhexan-1-ol in response to the stressor [53], while the second study found changes in the concentrations 1,2-ethanediol acetophenone, heptadecane, hexanedioic acid, dimethyl ester, benzyl alcohol, and benzothiazole [19]. However, in the first study, the biomarkers were found in the forehead samples, which might be produced from eccrine glands as cortisol metabolite VOCs, whereas in the second study the biomarkers were measured from apocrine glands (underarms).…”

“…In addition, heart rate and blood pressure measurements were recorded. It was found that four stress biomarkers (benzoic acid, n-decanoic acid, a xylene isomer, and 3-carene) were present, as can be seen in Figure 4 [53]. Notably, the identified biomarkers from both studies were different.…”

Advancements in Non-Invasive Biological Surface Sampling and Emerging Applications

“…Based on the study results, combining the sampling patches with a thermal desorption unit coupled to a secondary electrospray ionization and mass spectrometry (TD-SESI-MS) setup is a promising approach for unattended automation of analysis and could be employed in non-invasive fast screening of metabolites for personalized medicine. In a pilot study [38], Martin et al investigated changes in VOC profiles for stress-related biomarkers using PDMS devices placed on the foreheads of volunteer subjects for sample collection. The effect of stress on VOCs exhaled in breath was investigated previously [39], identifying six potential marker compounds.…”

“…In addition, PDMS films can be purchased or prepared in the laboratory using well defined protocols and can be easily shaped in any size. In addition, the thermal stability of PDMS enables the thermal desorption of extracted analytes from patches using large thermal desorption units connected to gas chromatography mass spectrometry (GC-MS) [35,36,38]. However, it is worth mentioning that before use PDMS patches require extensive cleaning and activation steps that might involve a considerable amount of preparation before sampling (4-24 h).…”

“…Patch type or other contact-based sampling methods [6,[34][35][36]38,[54][55][56] may not always be preferable for skin VOC analysis as contamination and introduction of non-volatile compounds is always a possibility. Headspace SPME is a commonly used sampling approach preferred for extracting volatiles present in various samples including complex matrices [57][58][59][60].…”