Salivary chromogranin a reflects autonomic regulation during “wake to sleep” and “sleep to wake” transitions

This study was conducted to determine the appropriate sampling time of the salivary stress markers, chromogranin A (CgA) and cortisol as objective indices of job stress assessment in adult females. The subjects were 20 approximately 39-year-old women (13 office workers, 11 sales-service workers, and 11 college students) who were eligible for the study and free of acute and chronic medical conditions. Salivary CgA and cortisol levels were determined by enzyme-linked immunosorbent assay (ELISA). Saliva samples were collected (2 ml each) at 7:00, 8:00, 10:30, 12:00, 17:30, and 22:30 on a typical day. Salivary CgA and cortisol levels, according to sampling time, were compared among the three groups using general linear model. The full version of the Korean Occupational Stress Scale (KOSS), which includes socioeconomic characteristics, health behavior, work-related characteristics, and BMI, was used to access the subjects' job stress. Multiple regression analysis of the job stressors identified by the KOSS was performed on salivary CgA and cortisol levels. The salivary CgA level peaked at 7:00 (time of awakening), then decreased and were maintained at a low level throughout the day, and increased slightly at 17:30. The salivary cortisol level increased steeply within the 1st hour after awakening, followed by a gradual decrease by 12:00, and was then maintained at a low level throughout the day. The salivary cortisol levels of subjects who worked < or = 5 days per week and graduated from the university were significantly lower at 8:00 (p=0.006). The salivary cortisol levels of non-smokers were significantly lower at 7:00 (p=0.040) and 8:00 (p=0.003) compared to smokers. There were no significant differences in salivary CgA and cortisol levels at 10:30 and 12:00 in general characteristics. The regression coefficients on salivary CgA level were significant with interpersonal conflict at 17:30 and job insecurity at 22:30. Regression coefficients on salivary cortisol level were significant with organizational system and total job stressors at 17:30. We suggest that the appropriate sampling times for the salivary stress markers, CgA and cortisol, are at 7:00 (time of awakening), 8:00 (1 hour after awakening), 17:30 (early evening), and 22:30 (before sleep).

To investigate the usefulness of salivary chromogranin A (CgA) and cortisol as stress markers, and the effects of distraction on the suppression of stress in children. We examined salivary CgA and cortisol responses before and after venipuncture in hospitalized children with and without distraction using a kaleidoscope. Salivary CgA levels immediately after venipuncture were significantly higher than those immediately before it, and at 60 min after venipuncture they were significantly lower than those immediately after it. However, salivary cortisol showed no significant differences at any of the three time points. In contrast, distracted by the kaleidoscope, there were no significant differences in salivary CgA and cortisol levels at all three time points. In children, salivary CgA level is a useful marker of stress. As an index of the effect of distraction, the measurement of salivary CgA is useful.

Salivary stress-related biomarkers in connection with periodontal disease have not been extensively studied. In addition to cortisol as a well-known marker of stress loading, chromogranin A (CgA) and α-amylase (AA) are supposed to link the activity of the neuroendocrine system to local and systemic immune functions and to be related to periodontitis. This study aims to determine CgA and AA in saliva and serum in periodontal health and disease to assess their potential relationship to periodontitis. Patients with aggressive (AgP) (n = 24) and chronic periodontitis (CP) (n = 34) as well as healthy control (CO) (n = 30) individuals participated in this study. CgA and AA were determined in saliva and serum with enzyme-linked immunosorbent assay and an adapted clinical amylase test; salivary cortisol was determined using mass spectrometry. Clinical parameters of periodontal disease were evaluated, and their possible correlations with stress-related biomarkers were assessed. Significantly higher CgA levels were found in the saliva of patients with AgP compared with those in patients with CP and CO individuals (P <0.001). Salivary cortisol levels were higher in the AgP group compared with those in patients with CP (P <0.05). No differences in serum CgA levels and salivary and serum AA activities were found among all groups. A positive correlation was revealed between salivary AA activity or salivary CgA levels and the extent of periodontitis (P <0.05). The results suggest an association of CgA and cortisol levels as well as AA activity in saliva with periodontitis, especially a significant relationship of salivary CgA and cortisol to AgP.

To evaluate the affective state biochemically and quantitatively in amyotrophic lateral sclerosis (ALS) patients using salivary chromogranin A (CgA) measurement. Twelve moderate and 12 terminal ALS patients defined using the ALS Health State Scale were studied. The correlation between salivary CgA levels and the 40-item ALS assessment questionnaire (ALSAQ-40) scores was investigated in 12 moderate ALS patients. Moreover, salivary CgA levels in 12 terminal ALS patients, in whom the emotional functioning score could not be assessed, were compared with those in 12 moderate ALS patients, 7 patients with tube-fed vascular dementia, and in 26 healthy volunteers. There were individual differences in salivary CgA levels in spite of similar severity of disease; however, mean salivary CgA levels in terminal ALS patients, in whom the emotional functioning score based on interview could not be assessed, was significantly higher (12.58+/-2.79 pmol/mL) than in patients with moderate ALS (6.36+/-1.62 pmol/mL, p<0.05), tube-fed vascular dementia (4.04+/-2.04 pmol/mL, p<0.01), and healthy volunteers (3.77+/-1.90 pmol/mL, p<0.01). Moreover, a statistically significant positive correlation was observed between salivary CgA levels and emotional functioning scores on ALSAQ-40 in moderate patients (r=0.892, p<0.01). Salivary CgA may be a useful and quantitative biochemical marker of the affective state, not only in moderate, but also in terminal ALS. Periodic salivary CgA measurements over the long term and/or in various situations could have therapeutic implications for the quality of life of these patients.

Introduction: Audiovisual Distraction (AVD), as a behaviour management technique, has gained significant importance in aiding patient cooperation during routine dental procedures. However, the scale at which it makes a difference needs to be evaluated. Objective approaches like measuring heart rate and pulse rates are unreliable methods. The quantification can be done using salivary Chromogranin A (CgA), a stress marker. Aim: To evaluate the use of AVD for reducing stress in children aged 4-7 years during dental treatment using salivary CgA. Materials and Methods: The present quasi-experimental study was conducted within the Department of Paediatric and Preventive Dentistry, Bharati Vidyapeeth (Deemed to be University) Dental College and Hospital, Pune, Maharashtra, India, from January 2022 to March 2022 after obtaining ethical clearance from the Institute and consent from parents. Six uncooperative children who required two Class-I restorative treatments for occlusal caries involving enamel and dentin were included in the study. The sample size was estimated using G*Power software v3.1.9.2 and calculated using t-tests. The treatment plan was divided into two appointments. In the first appointment, the cavity was prepared without the use of AVD. In the second appointment, AVD was incorporated during the dental procedure using the patient’s favourite cartoon. Unstimulated salivary samples were collected during both appointments, before and immediately after the procedure, which were sent to the laboratory for evaluation of CgA levels to gauge the stress levels during each appointment and the effect AVD has on the same. Results: Within the group without AV aids used, the mean salivary CgA levels showed a significant increase from 0.23 pmol/mg pretreatment to 1.26 pmol/mg protein after treatment. Within the group with AV aids, salivary CgA levels showed a significant reduction (p≤0.05) from 1.08 pmol/mg before treatment to 0.43 pmol/mg protein after treatment. There was also a significant difference in the change in salivary CgA levels from pre- to post-treatment between the two study groups. Conclusion: The study shows quantitatively that AVD reduced stress levels during dental treatment and therefore can be used as an adjunct for behaviour management. It can also be seen that Salivary CgA is a reliable short-term stress marker and can be used objectively to evaluate and quantify stress levels in children.

We assessed the stress relief effect of spa bathing by measuring sensitive salivary stress markers, cortisol and chromogranin A (CgA). From 12 healthy males, saliva samples were collected immediately before and after spa bathing, and 30 min after that. Salivary cortisol and CgA levels were determined by ELISA. Salivary cortisol levels decreased after spa bathing. This tendency was more pronounced in individuals with higher levels of stress. The high-stress group showed lower salivary CgA levels after spa bathing, while the low-stress group higher salivary CgA levels in the same condition. These findings suggest that the spa bathing has a moderate affect on the stress relief.

Salivary chromogranin A levels relate to fatigability after waking up.

Salivary chromogranin A (CgA) levels and salivary flow rates were measured to evaluate the stress relief effect of laughter on the young and the elderly. Thirty healthy volunteers (15 aged 20-25years; 15 aged 62-83years) performed a serial arithmetic task for 15min and then watched a comedy video for 30min. On a different day, as a control, they watched a non-humorous video after performing a task similar to the first one. Saliva samples were collected immediately before and after the arithmetic task, 30min after completing the task (immediately after watching the film), and 30 min after watching the film (60 min after completing mental task). Salivary CgA levels were determined by enzyme-linked immunosorbent assay. In the elderly group, salivary flow rates, which had declined by the end of the arithmetic task, were statistically significantly higher after watching the comedy video. In the young group, salivary CgA levels, which had increased by the end of the task, had statistically significantly declined after watching the comedy video. No such post-task changes were apparent in control results; in the young group, there was a statistically significant interprotocol difference in salivary CgA levels. These findings suggest that laughter may relieve stress, particularly in the young people.

To determine the changes in salivary chromogranin A (CgA) levels upon awakening in response to of stress by investigating the relationship between salivary CgA levels and the stress response as assessed by GHQ-28 tests. The study cohort comprised 40 healthy male university students (age range 19-22 years). Salivary CgA levels were measured at 7:00 a.m. (awakening) and at 7:30, 8:00, and 8:30 a.m. (after awakening). The salivary CgA level was 0.91 ± 0.20 and 0.42 ± 0.1 pmol/ml at 7:00 a.m. in students scoring low (n = 26) and high (n = 14), respectively, on the "severe depression" subscale. This difference in salivary CgA levels at 7:00 between high and low scorers was statistically significant (p < 0.05). Our findings indicate that depression may influence secretions of salivary CgA via chronic stress-related attenuation of the sympathetic-adrenomedullary system activity.

BackgroundsPsychological stress plays a role in the development of periodontal disease by influencing immune function and behavioral responses. Chromogranin A (CgA), a glycoprotein released due to activation of the sympathetic-adrenomedullary system, shows potential as a salivary biomarker for stress-related immune changes. This study aimed to assess salivary CgA levels in individuals with healthy and diseased periodontal conditions while investigating its correlation with clinical periodontal parameters and psychological stress.MethodsThis cross-sectional study involved 56 systemically healthy participants classified into groups based on their periodontal condition: periodontal health, gingivitis, Stage II, and Stage III periodontitis. Clinical periodontal parameters were assessed. Psychological stress levels were measured using the Beck Depression Inventory (BDI). Unstimulated saliva samples were collected and analyzed for CgA mRNA expression. Statistical analyses comprised ANOVA, Spearman’s correlation, and chi-square tests.ResultsSalivary CgA levels were significantly higher in individuals with Stage III periodontitis compared to those with periodontal health, gingivitis, or Stage II periodontitis (p < 0.01). No significant correlation was observed between salivary CgA levels and BDI scores.DiscussionAlthough salivary CgA levels were significantly elevated in patients with advanced periodontal disease, no direct associations were observed between CgA levels and individual clinical or psychological stress measures. These findings suggest that CgA may reflect systemic stress-related changes associated with disease severity rather than individual psychological status.

Burning mouth syndrome (BMS) is a poorly understood oral pain disorder characterized by a painful burning sensation in the oral cavity without any mucosal abnormalities. In this study, we evaluated the salivary cortisol and chromogranin A (CgA) levels of patients with BMS in comparison with age-matched controls. Subjects (n = 114) included 81 BMS patients and 33 controls. Patients with BMS were further classified into a subgroup of subjects who occasionally feel a burning sensation (BMS 1), and a subgroup of subjects who always feel a burning sensation (BMS 2). Salivary cortisol and CgA levels were measured using ELISA kits. All individuals with BMS had significantly higher cortisol and CgA levels than the controls did. Furthermore, when comparing the controls with each BMS subgroup, salivary levels of cortisol were significantly higher in both subgroups than controls. In contrast, the level of CgA was significantly higher in the BMS 2 subgroup only. Multiple regression analysis revealed a significant independent association between salivary levels of cortisol and BMS even after adjustment for gender, antidepressant or antianxiety drug use and hypertension (drug-treated). The study revealed that a significant association was observed between salivary cortisol levels and BMS.

Stress-induced scratching is an issue in patients with adult atopic dermatitis (AD). Symptoms of stress-induced AD are common in clinical practise. Salivary chromogranin A (CgA) level has research value as a possible index related to a patient's psychological stress. Using saliva, which is easily collectable, we compared two assessments of the severities of AD and stress with the levels of stress proteins in the saliva of 30 patients with AD in the Department of Dermatology of Shimane University between April 2015 and May 2017. The severities of AD and stress were assessed using the Scoring Atopic Dermatitis (SCORAD) score and State-Trait Anxiety Inventory score, respectively. Additionally, the assessments included those of personality using the Tokyo University Egogram (TEG)-II score and quality of life using the Dermatology Life Quality Index score. Simultaneously, we measured their salivary CgA levels. The change in salivary CgA per protein in patients with AD was correlated with their changes in SCORAD score (correlation coefficient, r = 0.596, P = 0.001) and objective SCORAD (r = 0.608, P < 0.001). The changes in CgA per protein correlated with those in TEG-II A (r = 0.370, P = 0.022), while the changes in SCORAD score correlated with those in DLQI (r = 0.309, P = 0.048). Our results suggest that changes in a patient's condition are reflective of the changes in the patient's stress. The changes in salivary CgA level in patients with AD correlated with the changes in their condition.

Effects of woodland walking on salivary stress markers cortisol and chromogranin A

To investigate the effect of snack eating on salivary cortisol and chromogranin A (CgA). From 14∶00 to 18∶00, starting two hours after consumption of a midday meal, saliva samples were collected every 30 minutes from 15 healthy males, 7 of whom (snack group) ate a snack immediately after the sampling at 15∶00. Salivary cortisol and CgA levels were determined by ELISA. Samples were controlled according to salivary flow rates. For the snack group, after snack consumption, salivary cortisol increased to exceed significance (p<0.05) at 15∶30 and rose even higher at 16∶00. In the control group, there was no such change. There was no significant change in salivary CgA in either the snack group or the control groups during the sampling period. These findings suggest that no food should be consumed for at least 90 mins before saliva sampling for cortisol determination and that salivary CgA is probably not affected by snack eating.

The purpose of this study was to evaluate the effect of type 2 diabetes mellitus (T2DM) on salivary function impairments according to glycemic control status and subsequently compare the concentration of chromogranin A (CHGA) with its genetic profile. Thirty-six patients with controlled T2DM, 36 with poorly controlled T2DM, and 38 nondiabetic subjects underwent salivary flow rate measurements by means of unstimulated labial (ULS), unstimulated whole (UWS), and stimulated whole saliva (SWS) collections. CHGA concentrations were determined in saliva and plasma with ELISA, and two CHGA polymorphisms (T-415C and Glu264Asp) were analyzed by polymerase chain reaction-restriction fragment length polymorphism. T2DM patients presented significantly lower ULS and UWS flow rates regardless of glycemic control status compared to controls (P = 0.002 and P = 0.027, respectively). The SWS flow rate in the poorly controlled T2DM was the lowest among the groups (P = 0.026). Significantly higher plasma and salivary CHGA levels were found in T2DM groups (P = 0.019 and P < 0.001, respectively). CHGA gene variants (T-415C and Glu264Asp) revealed significant differences between diabetics and control subjects when associated with lower salivary flow and higher salivary CHGA production (P < 0.05). T2DM causes abnormalities in the function of salivary glands. However, poorly controlled T2DM has the most influence on SWS flow rates. Our findings indicate an association between plasma and salivary CHGA levels and T2DM patients. Furthermore, the results suggest that CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary CHGA production in T2DM patients. Nevertheless, further epidemiological studies are required to elucidate this clinical implication. Salivary impairments and high levels of CHGA are associated with T2DM patients. In addition, CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary CHGA production in T2DM patients. This could be a significant insight to establish a role for salivary CHGA as a potential clinical biomarker to T2DM.