Determination of endocannabinoids and N-acylethanolamines in human hair with LC-MS/MS and their relation to symptoms of depression, burnout, and anxiety

Gao, Wei; Walther, Andreas; Wekenborg, Magdalena; Penz, Marlene; Kirschbaum, Clemens

doi:10.1016/j.talanta.2020.121006

Cited by 30 publications

(16 citation statements)

References 44 publications

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“…Related to this line of research is a study suggesting higher hair 1-AG and lower SEA levels in women with childhood maltreatment (Koenig et al, 2018). In a recent analysis, we further replicated significant negative crosssectional relations between hair AEA levels and anxiety and burnout, and on trend-level with depression symptoms in a sample of 207 individuals of the general population (Gao et al, 2020). However, a recent analysis comparing 21 depressed women with 27 nondepressed controls identified no differences between groups for hair endocannabinoids (Behnke et al, 2021).…”

Section: Introductionsupporting

confidence: 63%

“…For the quantification of endocannabinoids and glucocorticoids, three hair strands (each with a minimum of 20 mg of hair) were cut as close as possible to the scalp from the posterior vertex. Hair samples were processed and analyzed as described in our published protocols for glucocorticoids (Gao et al, 2013) and endocannabinoids (Gao et al, 2020). Sample preprocessing and subsequent biochemical analysis were conducted at the Dresden LabService GmbH (Tatzberg 47, 01307, Dresden, Germany).…”

Section: Endocannabinoid and Glucocorticoid Quantificationmentioning

confidence: 99%

“…Samples were cut into 3cm segments from the scalp-near site representing the integrated hormone concentration over the last three months (e.g. average hair growth rate 1cm per month; Wennig 2000) and weighted into 7.5 mg of whole, nonpulverized hair and subsequently washed with 2.5 ml isopropanol following the protocol by Gao et al (2020Gao et al ( , 2013. Biochemical analysis was conducted using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) described in detail elsewhere (Gao et al, 2016).…”

Section: Endocannabinoid and Glucocorticoid Quantificationmentioning

confidence: 99%

“…Based on the recognition of the functional interaction between the HPA axis and the ECS, endocannabinoids such as AEA and 2-AG/1-AG have been discussed on the one hand as potential biomarkers and on the other hand as factors that in concert with the HPA axis system may cause depression or stress-related syndromes such as burnout or as a consequence of the disorder be dysregulated (Behnke et al, 2021;Gao et al, 2020;Giacobbe et al, 2021;Hill et al, 2018). However, except for the present study, it has never been investigated wether the between-and within-person changes in depression or burnout symptoms are related to to endocannabinoid and cortisol levels using a baseline assessment and three annual followup examinations.…”

Section: Integration Of Findingsmentioning

confidence: 99%

“…That is, glucocorticoids such as cortisol -the main effector of the HPA axis -recruit endocannabinoid signaling and thereby the ECS modulates many of the neurobiological effects of glucocorticoids (Balsevich et al, 2017). The HPA axis together with the ECS are therefore regarded as two interlocking key regulatory systems implicated in the pathophysiology of depressive disorders (Hillard, 2017) and burnout (Gao et al, 2020). This perspective is substantiated by the fact that both, glucocorticoid receptors (GRs) as well as cannabinoid receptors (CBR) are expressed in all of the main brain structures involved in depressive disorders and burnout such as the hypothalamus, hippocampus, habenula, cortex, limbic system and amygdala (Biselli et al, 2019;Gururajan et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Disaggregating between- and within-person relations for depression and burnout symptoms with cumulative hair cortisol and endocannabinoid concentrations: A multilevel analysis of four annual assessment waves

Walther¹,

Kirschbaum²,

Wehrli³

et al. 2021

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Background: The endocannabinoid system (ECS) is increasingly being recognized as key regulatory system coupled with the glucocorticoid system implicated in the pathophysiology of stress-related mental disorders. However, prior studies examining the ECS in depression or burnout have been inconclusive, of small sample size or of cross-sectional nature limiting interpretations of causal inferences or time-dependent effects.Methods: In a prospective community based cohort study including 128 individuals (women: 108), depression (PHQ-9) and burnout symptoms (MBI-GS) as well as hair cortisol and endocannabinoids were measured annually over four years. Cortisol, arachidonylethanolamide (AEA) and 2-arachidonyl-sn-glycerol/1-arachidonyl-sn-glycerol (2-AG/1-AG) were extracted from 3 cm hair segments reflecting cumulative concentrations of the last 3 months prior hair sampling.Results: Cross sectional group comparisons at baseline revealed reduced cortisol and AEA levels in the group with a positive major depressive disorder screening compared to individuals with low depression symptomatology (both p < .05). Cortisol was also reduced in the group with a positive burnout screening compared to individuals with a negative screening at baseline (p < .05). Longitudinal multilevel analysis, showed for the total sample that a within-person increase in burnout symptoms was associated with a decrease in cortisol levels over time (p < .05). In the male subsample, a between-person increase in AEA levels across time was associated with a decrease in depression symptoms and vice versa. However, a within-person increase of AEA levels across time was associated with an increase in depression symptoms and vice versa (both p < .05). Further, a within-person increase in burnout symptoms lead to a significant increase in AEA levels in the male subsample (p < .05).Conclusions: While cross-sectional analyses suggest higher depression or burnout symptomatology to be associated with reduced cortisol and AEA release, longitudinal analyses disaggregating between- and within-person effects reveal a complex pattern. A within-person increase in burnout symptoms precedes a decrease in cortisol secretion suggesting an exhaustion of the HPA axis. Between-person analysis show only for men a negative association between depression symptoms and AEA levels over time. However, within-person effects, indicate an increase in depression symptoms to preced and to follow an increase in AEA levels, suggesting a dynamic counterregulatory mechanism between the EC and depression in men differing on the between- and within-person levels. These longitudinal associations further elucidate the time and sex dependent relation between depression, burnout, glucocorticoid and endocannabinoid secretion.

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Section: Introductionsupporting

confidence: 63%

Section: Endocannabinoid and Glucocorticoid Quantificationmentioning

confidence: 99%

Section: Endocannabinoid and Glucocorticoid Quantificationmentioning

confidence: 99%

Section: Integration Of Findingsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Disaggregating between- and within-person relations for depression and burnout symptoms with cumulative hair cortisol and endocannabinoid concentrations: A multilevel analysis of four annual assessment waves

Walther¹,

Kirschbaum²,

Wehrli³

et al. 2021

Preprint

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Endocannabinoid and steroid analysis in infant and adult nails by LC–MS/MS

et al. 2022

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A common method to quantify chronic stress is the analysis of stress markers in keratinized matrices such as hair or nail. In this study, we aimed to validate a sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the combined quantification of steroid hormones and endocannabinoids (eCBs) in the keratinized matrix nail. Furthermore, we aimed to investigate the suitability of the nail matrix for the detection of these stress markers in a pilot study. An LC–MS/MS method was used for the simultaneous identification and quantification of four eCBs (2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA)) and five steroid hormones (cortisol, cortisone, androstenedione, progesterone, testosterone) in human nails using a surrogate analyte method for each analyte. The method was validated in terms of selectivity, response factor, linearity, limit of quantification (LOQ), precision, accuracy, matrix effect, recovery, robustness, and autosampler stability. Nail samples were extracted for 1 h with methanol following a clean-up with a fully automated supported liquid extraction (SLE). The influence of nail weight on the quantification was investigated by using 0.5–20 mg of nail sample. As a proof of concept, nail samples (N = 57) were analyzed from a cohort representing newborns (1 month old), children (between 1 and 10 years), and adults (up to 43 years). It could be shown that the established workflow using a 1 hour extraction and clean-up by SLE was very robust and resulted in a short sample preparation time. The LC–MS/MS method was successfully validated. Matrix effects with ion enhancement occurred mainly for 2-AG. Sample weights below 5 mg showed variations in quantification for some analytes. Certain analytes such as PEA and progesterone could be accurately quantified at a sample weight lower than 5 mg. This is the first study where steroids and eCBs could be simultaneously detected and quantified in infant and adult nails. These results show that nails may serve as an alternative keratinized matrix (compared to hair) for the retrospective monitoring of cumulative eCB and steroid hormone levels. The combined assessment of eCBs and steroids from nails could provide a new approach to gain new insights into stress exposure in newborns and adults. Graphical abstract

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Monitoring of age- and gender-related alterations of endocannabinoid levels in selected brain regions with the use of SPME probes

et al. 2023

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Introduction The endocannabinoid system consists of different types of receptors, enzymes and endocannabinoids (ECs), which are involved in several physiological processes, but also play important role in the development and progression of central nervous system disorders. Objectives The purpose of this study was to apply precise and sensitive methodology for monitoring of four ECs, namely anandamide (AEA), 2-arachidonoyl glycerol (2-AG), N-arachidonoyl dopamine (NADA), 2-arachidonyl glyceryl ether (2-AGe) in selected brain regions of female and male rats at different stages of development (young, adult and old). Methods Biocompatible solid-phase microextraction (SPME) probes were introduced into the intact (non-homogenized) brain structures for isolation of four ECs, and the extracts were subjected to LC–MS/MS analysis. Two chemometric approaches, namely hierarchical cluster analysis (HCA) and Principal Component Analysis (PCA) were applied to provide more information about the levels of 2-AG and AEA in different brain structures. Results 2-AG and AEA were extracted and could be quantified in each brain region; the level of 2-AG was significantly higher in comparison to the level of AEA. Two highly unstable ECs, NADA and 2-AGe, were captured by SPME probes from intact brain samples for the first time. Conclusion SPME probes were able to isolate highly unstable endogenous compounds from intact tissue, and provided new tools for precise analysis of the level and distribution of ECs in different brain regions. Monitoring of ECs in brain samples is important not only in physiological conditions, but also may contribute to better understanding of the functioning of the endocannabinoid system in various disorders.

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Determination of endocannabinoids and N-acylethanolamines in human hair with LC-MS/MS and their relation to symptoms of depression, burnout, and anxiety

Cited by 30 publications

References 44 publications

Disaggregating between- and within-person relations for depression and burnout symptoms with cumulative hair cortisol and endocannabinoid concentrations: A multilevel analysis of four annual assessment waves

Disaggregating between- and within-person relations for depression and burnout symptoms with cumulative hair cortisol and endocannabinoid concentrations: A multilevel analysis of four annual assessment waves

Endocannabinoid and steroid analysis in infant and adult nails by LC–MS/MS

Monitoring of age- and gender-related alterations of endocannabinoid levels in selected brain regions with the use of SPME probes

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