A case study of Duchenne muscular dystrophy caused by Alu element insertion in DMD gene and analysis of its gray-hair symptoms.

Duchenne muscular dystrophy (DMD) is a severe X-linked recessive genetic disorder caused by mutations in the DMD gene, which leads to a deficiency of the dystrophin protein. The main mutation types of this gene include exon deletions and duplications, point mutations, and insertions. These mutations disrupt the normal expression of dystrophin, ultimately leading to the disease. In this study, we reported a case of DMD caused by an insertion mutation in exon 59 (E59) of the DMD gene. The affected child exhibited significant abnormalities in related biochemical markers, early symptoms of DMD, and multiple gray hair. His mother and sister were carriers with slightly abnormal biochemical markers. The mother had mild clinical symptoms, while the sister had no clinical symptoms. Other family members were genetically and physically normal. Sequencing and sequence alignment revealed that the inserted fragment was an Alu element from the AluYa5 subfamily. This insertion produced two stop codons and a polyadenylate (polyA) tail. To understand the impact of this insertion on the DMD gene and its association with clinical symptoms, exonic splicing enhancer (ESE) prediction indicated that the insertion did not affect the splicing of E59. Therefore, we speculated that the insertion sequence would be present in the mRNA sequence of the DMD gene. The two stop codons and polyA tail likely terminate translation, preventing the production of functional dystrophin protein, which may be the mechanism leading to DMD. In addition to typical DMD symptoms, the child also exhibited premature graying of hair. This study reports, for the first time, a case of DMD caused by the insertion of an Alu element into the coding region of the DMD gene. This finding provides clues for studying gene mutations induced by Alu sequence insertion and expands the understanding of DMD gene mutations.

In vitro biotransformation of 3-methylmethcathinone (3-MMC) through incubation with human liver microsomes and cytosol and application to in vivo samples.

Synthetic cathinones are the second largest group of new psychoactive substances (NPS) monitored by the European Monitoring Centre for Drugs and Drug Addiction. Although 3-methylmethcathinone (3-MMC, C11H15NO) is legally banned in many countries, it is readily available for purchase online and on the street. Due to the scarcity of information regarding the pharmacokinetic and toxicological profile of 3-MMC, understanding its biotransformation pathways is crucial in determining its potential toxicity in humans and in the development of analytical methods for screening of human matrices. To gain more insight, Phase I and Phase II in vitro biotransformation of 3-MMC was investigated using human liver microsomes and human liver cytosol. Suspect and non-target screening approaches were employed to identify metabolites. To confirm in vitro results in an in vivo setting, human matrices (i.e., plasma, urine, saliva and hair) positive for 3-MMC (n=31) were screened. In total three biotransformation products were identified in vitro: C11H15NO2 (a hydroxylated derivate), C11H17NO (a keto-reduced derivate) and C10H13NO (an N-desmethyl derivate). All three were confirmed as human metabolites in respectively 16 %, 52 % and 42 % of the analysed human samples. In total, 61 % of the analysed samples were positive for at least one of the three metabolites. Interestingly, three urine samples were positive for all three metabolites. The presence of 3-MMC in saliva and hair indicates its potential applicability in specific settings, e.g., roadside testing or chronic consumption analysis. To our knowledge, C11H17NO was not detected before in vivo. Although some of these metabolites have been previously suggested in vitro or in a single post mortem case report, a wide in vivo confirmation including the screening of four different human matrices was performed for the first time. These metabolites could serve as potential human biomarkers to monitor human 3-MMC consumption effectively.

Is premorbid stress assessed by hair cortisol concentration linked to Takotsubo syndrome? Results from a pilot study.

INTRODUCTION: The pathophysiology of Takotsubo syndrome (TTS) is not completely understood and the role of chronic stress is among the main mechanistic links. The aim of this study was to explore whether accumulating hair cortisol concentration (HCC), a novel biomarker of chronic stress, is associated with the occurrence of TTS. METHODS: A consecutive series of 18 TTS patients and 36 age and sex matched healthy controls were included in our analysis. Hair samples were collected from participants'' vertex. The proximal 2.5 cm of hair was cut in equal parts of 0.5 cm, reflecting mean cortisol levels in time intervals of 0-15, 15-30, 30-45, 45-60 and 60-75 days prior to hair collection. RESULTS: HCC was higher in TTS group compared to controls at any time point and increased over time starting from 75 days prior to the event. The rate of HCC increase was significantly higher in TTS patients versus controls (beta of interaction = 0.48; 95%CI: 0.36-0.60; p < 0.001). CONCLUSIONS: The steadily increasing trend of HCC in TTS patients suggests that the additive effect of multiple stressful events over several weeks prior TTS onset may disrupt cortisol homeostasis and play a role in TTS pathophysiology.

Hair cortisol and substance use among women currently experiencing intimate partner violence: The role of PTSD symptom severity.

INTRODUCTION: Substance use is highly prevalent among women experiencing intimate partner violence (IPV) and has been associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and resulting cortisol response. Posttraumatic stress disorder (PTSD) symptoms may play an important role in exacerbating the association between cortisol levels and substance use behaviors. PURPOSE: This study examined the role of PTSD symptoms in the relation between cortisol and past month substance use behaviors. The current study used hair cortisol as an index of past 30-day HPA-axis functioning and ecological momentary assessment (EMA) to characterize substance use behaviors more accurately over a 30-day period. METHOD: Participants were 90 community women who had experienced physical or sexual IPV in the past 30 days by their current male partner and used any amount of alcohol or drugs (M age = 40.71; 54.4 % white). Participants completed (a) a baseline interview, (b) EMA for 30-days, and (c) a follow up interview where they were asked to provide a hair sample for cortisol analyses. Data collection took place from 2018 to 2020. RESULTS: PTSD severity moderated the relations between cortisol and days of drinking and binge drinking. In the context of high PTSD symptomology, women with high cortisol levels spent, on average, an additional 7.4 days drinking and 8.1 days binge drinking in the past 30 days compared to women with low cortisol levels, in a model adjusted for age. CONCLUSIONS: Results highlight the prominent role of PTSD symptoms in the association between cortisol and alcohol use among women experiencing IPV.

Two-year course of non-suicidal self-injury in an adolescent clinical cohort: The role of childhood adversity in interaction with cortisol secretion.

AIM: Non-suicidal self-injury (NSSI) is a highly prevalent phenomenon during adolescence. Nonetheless, research on predictors of the clinical course of NSSI over time is still scarce. The present study aimed at investigating the impact of adverse childhood experiences (ACE) and hypothalamus-pituitary-adrenal (HPA) axis functioning on the longitudinal course of NSSI. METHODS: In a sample of n = 51 help-seeking adolescents engaging in NSSI, diurnal cortisol secretion (CAR, cortisol awakening response; DSL, diurnal slope), hair cortisol concentrations and ACE were assessed at baseline. Clinical outcome was defined by change in the frequency of NSSI in the past 6 months measured 12 and 24 months after the baseline assessments. Mixed-effects linear regression models were used to test for effects of ACE and HPA axis functioning on the course of NSSI. RESULTS: ACE and HPA axis functioning did not show main but interaction effects in the prediction of NSSI frequency over time: Adolescents with a low severity of ACE and either an increased CAR or a flattened DSL showed a steep decline of NSSI frequency in the first year followed by a subsequent increase of NSSI frequency in the second year. CONCLUSIONS: Our findings could be interpreted in the sense of high diurnal cortisol concentrations in the absence of ACE being favorable for clinical improvement on the short-term but bearing a risk of allostatic load and subsequent increase of NSSI frequency. In contrast, adolescents with severe ACE may benefit from elevated cortisol concentrations leading to slower but lasting decreases of NSSI frequency.

Characterization of hair cortisol concentration pre-conception and during pregnancy.

BACKGROUND: The hypothalamic pituitary adrenal (HPA) axis is a system involved in stress and pregnancy regulation, and hair cortisol concentration (HCC) is a promising biomarker of its activity. Assessing factors that influence HCC in the prenatal period is critical to understand whether and how HPA axis (dys-)regulation influences maternal health and child development, particularly in high-risk populations from low- and middle-income countries (LMICs). AIMS: This study aimed at characterizing preconception and pregnancy HCC with respect to multiple sociodemographic, pregnancy-related, and hair-related factors. METHODS: In a sample of N = 2581 pregnant women in Perú, participants from two cohort studies provided a 6 cm scalp hair sample at three prenatal timepoints. Each hair sample was cut into two segments of 3 cm that represent cortisol secretion at four times: preconception, first-, second- and third trimester of pregnancy. Hair cortisol was extracted using liquid chromatography tandem mass spectrometry (LC-MS/MS). Spearman correlations, paired t-tests, and ANOVA were used to assess differences in log-transformed values of HCC (logHCC) across maternal sociodemographic, pregnancy-related, and hair-related factors. Multivariable linear regressions were used to examine independent associations of HCCs with selected correlates. RESULTS: Mean logHCC values showed an increase across the four prenatal periods. Preconception BMI was consistently associated with HCC in all three trimesters, while difficulty accessing basic foods, education, hair dyeing, and infant sex showed time-specific associations with HCCs. In sensitivity analyses, we detected no substantial segment effects in the associations of HCCs with maternal characteristics. CONCLUSION: This study is the largest to characterize HCC in pregnant women from a LMIC. Our findings provide a foundation for the use of HCC as a biomarker of prenatal HPA axis activity for future studies. This foundation may contribute to finding valid biomarkers of stress-response systems to promote maternal and child health.

Oxidative stress in hair follicle development and hair growth: Signalling pathways, intervening mechanisms and potential of natural antioxidants.

Hair follicle development and hair growth are regulated by multiple factors and multiple signalling pathways. The hair follicle, as an important skin appendage, is the basis for hair growth, and it has the functions of safeguarding the body, perceiving the environment and regulating body temperature. Hair growth undergoes a regular hair cycle, including anagen, catagen and telogen. A small amount of physiological shedding of hair occurs under normal conditions, always in a dynamic equilibrium. Hair loss occurs when the skin or hair follicles are stimulated by oxidative stress, inflammation or hormonal disorders that disrupt the homeostasis of the hair follicles. Numerous researches have indicated that oxidative stress is an important factor causing hair loss. Here, we summarize the signalling pathways and intervention mechanisms by which oxidative stress affects hair follicle development and hair growth, discuss existing treatments for hair loss via the antioxidant pathway and provide our own insights. In addition, we collate antioxidant natural products promoting hair growth in recent years and discuss the limitations and perspectives of current hair loss prevention and treatment.

Hair Thickness Growth Effect of Adenosine Complex in Male-/Female-Patterned Hair Loss via Inhibition of Androgen Receptor Signaling.

Aging (senescence) is an unavoidable biological process that results in visible manifestations in all cutaneous tissues, including scalp skin and hair follicles. Previously, we evaluated the molecular function of adenosine in promoting alopecia treatment in vitro. To elucidate the differences in the molecular mechanisms between minoxidil (MNX) and adenosine, gene expression changes in dermal papilla cells were examined. The androgen receptor (AR) pathway was identified as a candidate target of adenosine for hair growth, and the anti-androgenic activity of adenosine was examined in vitro. In addition, ex vivo examination of human hair follicle organ cultures revealed that adenosine potently elongated the anagen stage. According to the severity of alopecia, the ratio of the two peaks (terminal hair area/vellus hair area) decreased continuously. We further investigated the adenosine hair growth promoting effect in vivo to examine the hair thickness growth effects of topical 5% MNX and the adenosine complex (0.75% adenosine, 1% penthenol, and 2% niacinamide; APN) in vivo. After 4 months of administration, both the MNX and APN group showed significant increases in hair density (MNX + 5.01% (p < 0.01), APN + 6.20% (p < 0.001)) and thickness (MNX + 5.14% (p < 0.001), APN + 10.32% (p < 0.001)). The inhibition of AR signaling via adenosine could have contributed to hair thickness growth. We suggest that the anti-androgenic effect of adenosine, along with the evaluation of hair thickness distribution, could help us to understand hair physiology and to investigate new approaches for drug development.

DNA Microarray and Bioinformatic Analysis Reveals the Potential of Whale Oil in Enhancing Hair Growth in a C57BL/6 Mice Dorsal Skin Model.

Much research has been conducted to determine how hair regeneration is regulated, as this could provide therapeutic, cosmetic, and even psychological interventions for hair loss. The current study focused on the hair growth effect and effective utilization of fatty oil obtained from Bryde's whales through a high-throughput DNA microarray approach in conjunction with immunohistochemical observations. The research also examined the mechanisms and factors involved in hair growth. In an experiment using female C57BL/6J mice, the vehicle control group (VC: propylene glycol: ethanol: water), the positive control group (MXD: 3% minoxidil), and the experimental group (WO: 20% whale oil) were topically applied to the dorsal skin of the mouse. The results showed that 3% MXD and 20% WO were more effective than VC in promoting hair growth, especially 20% WO. Furthermore, in hematoxylin and eosin-stained dorsal skin tissue, an increase in the number of hair follicles and subcutaneous tissue thickness was observed with 20% WO. Whole-genome transcriptome analysis also confirmed increases for 20% WO in filaggrin (Flg), a gene related to skin barrier function; fibroblast growth factor 21 (Fgf21), which is involved in hair follicle development; and cysteine-rich secretory protein 1 (Crisp1), a candidate gene for alopecia areata. Furthermore, the results of KEGG pathway analysis indicated that 20% WO may have lower stress and inflammatory responses than 3% MXD. Therefore, WO is expected to be a safe hair growth agent.

Hair steroid before and after COVID-19 in preschoolers: the moderation of family characteristics.

BACKGROUND: Frequent or prolonged exposure to stressors may jeopardize young children's health. The onset of the COVID-19 pandemic, coupled with disruptions in daily routines and social isolation resulting from public health preventive measures, have raised concerns about its potential impact on children' experienced stress, particularly for young children and vulnerable families. However, whether the pandemic was accompanied by changes in physiological stress remains unknown as perceived stress is not a good proxy of physiological stress. This study examined if preschoolers showed increasing hair steroid concentrations following the onset of the COVID-19 pandemic and whether family characteristics may have exacerbated or buffered these changes. METHODS: 136 preschoolers (2-4 years) provided hair for steroid measurement (cortisol, dehydroepiandrosterone (DHEA), cortisone, cortisol-to-DHEA ratio, cortisol-to-cortisone ratio) in October-November 2019 (T0) and in July-August 2020 (T1). A 2-centimeter hair segment was analyzed, reflecting steroid production over the two months leading up to collection. Family income, conflict resolution and lack of cohesion, as well as parents' COVID-19 stress were reported by parents. Linear mixed models for repeated measures and Bayes factors were used. RESULTS: No significant changes were noted from before to after the onset of the COVID-19 pandemic for most hair steroids. However, a moderating role of family conflict resolution was noted. Children living with parents with a better ability to resolve conflicts had lower levels of DHEA compared to those who had more difficulty managing conflicts. Additionally, lower levels of family cohesion and income were linked to some steroids, especially DHEA, suggesting that these factors may relate to children's physiological stress. Finally, boys had higher DHEA levels than girls. CONCLUSION: Our findings suggest that stress biomarkers were comparable from before to during the COVID-19 pandemic. This observation holds true despite the pandemic being perceived by many as a novel, unpredictable, and potentially threatening event. Findings further suggest that family characteristics are associated with hair steroid, especially DHEA, which deserves further investigation.

[Research progress in regulation of hair growth by dermal adipose tissue].

Objective: To summarize the dynamic and synchronized changes between the hair cycle and dermal adipose tissue as well as the impact of dermal adipose tissue on hair growth, and to provide a new research idea for the clinical treatment of hair loss. Methods: An extensive review of relevant literature both domestic and international was conducted, analyzing and summarizing the impact of dermal adipose precursor cells, mature dermal adipocytes, and the processes of adipogenesis in dermal adipose tissue on the transition of hair cycle phases. Results: Dermal adipose tissue is anatomically adjacent to hair follicles and closely related to the changes in the hair cycle. The proliferation and differentiation of dermal adipose precursor cells promote the transition of hair cycle from telogen to anagen, while mature adipocytes can accelerate the transition from anagen to catagen of the hair cycle by expressing signaling molecules, with adipogenesis in dermal adipose tissue and hair cycle transition signaling coexistence. Conclusion: Dermal adipose tissue affects the transition of the hair cycle and regulates hair growth by secreting various signaling molecules. However, the quantity and depth of existing literature are far from sufficient to fully elucidate its prominent role in regulating the hair cycle, and the specific regulatory mechanisms needs to be further studied.

Integrative analysis of Iso-Seq and RNA-seq data reveals transcriptome complexity and differential isoform in skin tissues of different hair length Yak.

BACKGROUND: The hair follicle development process is regulated by sophisticated genes and signaling networks, and the hair grows from the hair follicle. The Tianzhu white yak population exhibits differences in hair length, especially on the forehead and shoulder region. However, the genetic mechanism is still unclear. Isoform sequencing (Iso-seq) technology with advantages in long reads sequencing. Hence, we combined the Iso-seq and RNA-seq methods to investigate the transcript complexity and difference between long-haired yak (LHY) and normal-haired yak (NHY). RESULTS: The hair length measurement result showed a significant difference between LHY and NHY on the forehead and the shoulder (P-value < 0.001). The skin samples from the forehead and the shoulder of LHY and NHY were pooled for isoform sequencing (Iso-seq). We obtained numerous long transcripts, including novel isoforms, long non-coding RNA, alternative splicing events, and alternative polyadenylation events. Combined with RNA-seq data, we performed differential isoforms (DEIs) analysis between LHY and NHY. We found that some hair follicle and skin development-related DEIs, like BMP4, KRT2, IGF2R, and COL1A2 in the forehead skin; BMP1, KRT1, FGF5, COL2A1, and IGFBP5 in the shoulder skin. Enrichment analysis revealed that DEIs in both two comparable groups significantly participated in skin and hair follicle development-related pathways, like ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathways. The results indicated that the hair follicle development of Tianzhu white yak may influence the hair length difference. Besides, the protein-protein interaction (PPI) network of DEIs showed COL2A1 and COL3A1 exhibited a high degree of centrality, and these two genes were suggested as potential candidates for the hair length growth of Tianzhu white yak. CONCLUSIONS: The results provided a comprehensive analysis of the transcriptome complexity and identified differential transcripts that enhance our understanding of the molecular mechanisms underlying the variation in hair length growth in Tianzhu white yak.

Dissecting hair breakage in alopecia areata: the central role of dysregulated cysteine homeostasis.

In the initial stages of Alopecia Areata (AA), the predominance of hair breakage or exclamation mark hairs serves as vital indicators of disease activity. These signs are non-invasive and are commonly employed in dermatoscopic examinations. Despite their clinical salience, the underlying etiology precipitating this hair breakage remains largely uncharted territory. Our exhaustive review of the existing literature points to a pivotal role for cysteine-a key amino acid central to hair growth-in these mechanisms. This review will probe and deliberate upon the implications of aberrant cysteine metabolism in the pathogenesis of AA. It will examine the potential intersections of cysteine metabolism with autophagy, ferroptosis, immunity, and psychiatric manifestations associated with AA. Such exploration could illuminate new facets of the disease's pathophysiology, potentially paving the way for innovative therapeutic strategies.

Biotransformation of Cacumen platycladi Extract by Lactiplantibacillus plantarum CCFM1348 Promotes Hair Growth in Mice.

Cacumen platycladi (CP) is a frequently used traditional Chinese medicine to treat hair loss. In this study, CP fermented by Lactiplantibacillus plantarum CCFM1348 increased the proliferation of human dermal papilla cells. In an in vivo assay, compared to nonfermented CP, postbiotics (fermented CP) and synbiotics (live bacteria with nonfermented CP) promoted hair growth in mice. The Wnt/ß-catenin signaling pathway plays crucial roles in the development of hair follicles, including growth cycle restart and maintenance. Both postbiotics and synbiotics upregulated ß-catenin, a major factor of the Wnt/ß-catenin signaling pathway. Postbiotics and synbiotics also increased the vascular endothelial growth factor expression and decreased the BAX/Bcl2 ratio in the dorsal skin of mice. These results suggest that fermented CP by L. plantarum CCFM1348 may promote hair growth through regulating the Wnt/ß-catenin signaling pathway, promoting the expression of growth factors and reducing apoptosis.

Cross-sectional associations of self-perceived stress and hair cortisol with metabolic outcomes and microvascular complications in type 2 diabetes.

Introduction: Increasing evidence supports chronic psychological stress as a risk factor for the development of type 2 diabetes. Much less is known, however, about the role of chronic stress in established diabetes. Methods: The aim of the current study was to comprehensively assess chronic stress in a sample of 73 patients with type 2 diabetes and 48 non-diabetic control participants, and to investigate associations with indicators of glycemic control (HbA1c), insulin resistance (HOMA-IR), ß-cell functioning (C-peptide), illness duration, and the presence of microvascular complications. Chronic stress was measured using questionnaires [the Perceived Stress Scale (PSS), the Screening Scale of the Trier Inventory of Chronic Stress (SSCS), the Perceived Health Questionnaire (PHQ) as well as the Questionnaire on Stress in Patients with Diabetes-Revised (QSD-R)]; hair cortisol was used as a biological indicator. Results: We found that patients with type 2 diabetes had higher levels of hair cortisol in comparison to the control group (F(1,112) = 5.3; p = 0.023). Within the diabetic group, higher hair cortisol was associated with a longer duration of the illness (r = 0.25, p = 0.04). General perceived stress did not show significant associations with metabolic outcomes in type 2 diabetes patients. In contrast, higher diabetes-related distress, as measured with the QSD-R, was associated with lower glycemic control (r = 0.28, p = 0.02), higher insulin resistance (r = 0.26, p = 0.03) and a longer duration of the illness (r = 0.30, p = 0.01). Discussion: Our results corroborate the importance of chronic psychological stress in type 2 diabetes. It appears, however, that once type 2 diabetes has developed, diabetes-specific distress gains in importance over general subjective stress. On a biological level, increased cortisol production could be linked to the course of the illness.

Childhood trauma and hair cortisol response over the year following onset of a chronic life event stressor.

OBJECTIVE: Childhood trauma may contribute to poor lifelong health in part through programming of the HPA-axis response to future life stressors. To date, empirical evidence shows an association of childhood trauma with dysregulation of the HPA-axis and blunted cortisol reactivity to acute stressors. Here, we conduct an initial examination of childhood trauma as a moderator of changes over time in perceived stress levels and HPA-axis response to a major chronic stressor in adulthood. METHODS: Participants were 83 maternal caregivers of children newly diagnosed with cancer who completed the Childhood Trauma Questionnaire (CTQ), and who, over the year following their child's cancer diagnosis, had hair samples collected up to 7 times for the assessment of cortisol and completed monthly measures of perceived stress. RESULTS: CTQ scores were in the expected range for a community sample and associated with changes in perceived stress and cortisol concentration over time (γ =.003, p =.002; γ = -.0004, p =.008, respectively) independently of age, education, treatment intensity and randomization to stress management intervention. Maternal caregivers who endorsed lower childhood trauma showed a steeper decline in perceived stress and a larger increase in cortisol levels across the year than caregivers who recalled more childhood trauma. CONCLUSIONS: Findings extend animal models and studies that examine cortisol reactivity to acute stressors and suggest that childhood trauma may program a phenotype that is more psychologically reactive but shows a blunted HPA-axis response to chronic stress. While adaptive in the short-term, this early life programming may incur long-term costs for health. Further work is warranted to examine this possibility.

Associations of schizophrenia with the activities of the HPA and HPG axes and their interactions characterized by hair-based biomarkers.

BACKGROUND: Past studies on schizophrenia (SCZ) and the stress-sensitive neuroendocrine systems have mostly focused on a single system and traditionally utilized acute biomarkers (e.g., biomarkers from blood, urine and saliva) that poorly match the chronic course of schizophrenia in time span. Using eight biomarkers in hair, this study aimed to explore the functional characteristics of SCZ patients in the hypothalamic-pituitary-adrenocortical (HPA) and hypothalamic-pituitary-gonadal (HPG) axes and the interaction between the two axes. METHODS: Hair samples were taken from 137 SCZ patients and 73 controls. The SCZ patients were diagnosed by their attending physician according to the Diagnostic and Statistical Manual of Mental Disorders IV and were clinically stable after treatment. Gender, age, BMI, frequency of hair washing, marital status, education level, family history of mental illness and clozapine dosage were concurrently collected as covariates. The 10-item perceived stress scale (PSS-10) and the social readjustment rating scale were used to assess chronic stress status in SCZ patients. Eight hair biomarkers, cortisol, cortisone, dehydroepiandrosterone (DHEA), testosterone, progesterone, cortisol/cortisone, cortisol/DHEA and cortisol/testosterone, were measured by high performance liquid chromatography tandem mass spectrometer. Among them, cortisol, cortisone, DHEA and cortisol/DHEA reflected the functional activity of the HPA axis, and testosterone and progesterone reflected the functional activity of the HPG axis, and cortisol/cortisone reflected the activity of 11ß-hydroxysteroid dehydrogenase types 2 (11ß-HSD 2), and cortisol/testosterone reflected the HPA-HPG interaction. RESULTS: SCZ patients showed significantly higher cortisone and cortisol/testosterone than controls (p<0.001, η²p=0.180 and p=0.015, η²p=0.031), lower testosterone (p=0.009, η²p=0.034), progesterone (p<0.001, η²p=0.069) and cortisol/cortisone (p=0.001, η²p=0.054). There were significant intergroup differences in male and female progesterone (p=0.003, η²p=0.088 and p=0.030, η²p=0.049) and female testosterone (p=0.028, η²p=0.051). In SCZ patients, cortisol, cortisol/cortisone, cortisol/DHEA and cortisol/testosterone were positively associated with PSS-10 score (ps<0.05, 0.212

Stability and inter-family associations of hair endocannabinoid and N-acylethanolamines across the perinatal period in mothers, fathers, and children.

Analysis of endocannabinoids (ECs) and N-acylethanolamines (NAEs) in hair is assumed to retrospectively assess long-term EC/NAE concentrations. To inform their use, this study investigated stability of EC/NAE hair concentrations in mothers, fathers, and their children across the perinatal period as well as associations between family members. In a prospective cohort study, EC (AEA, 1-AG/2-AG) and NAE (SEA, PEA, OEA) levels were quantified in hair samples taken four times in mothers (n = 336) and their partners (n = 225) from pregnancy to two years postpartum and in offspring (n = 319) from shortly after birth to two years postpartum. Across the perinatal period, maternal and paternal hair ECs/NAEs showed poor multiple-test consistency (16-36%) and variable relative stability, as well as inconsistent absolute stability for mothers. Regarding children, hair ECs/NAEs evidenced poor multiple-test consistency (4-19%), no absolute stability, and either no or variable relative stability. Hair ECs/NAEs showed small to medium significant associations across the perinatal period within couples and parent-child dyads. Findings suggest hair ECs/NAEs during the perinatal period possess variable stability in adults, albeit more stability in fathers than mothers in this time. This highlights the need to further investigate factors associated with changes in hair ECs/NAEs across time. The first two years of life may be a dynamic phase for the endocannabinoid system in children, potentially characterized by complex within-family correspondence that requires further systematic investigation.