Increased Cortisol Levels Research Articles

Immuno-Graphene Field-Effect Transistor-Based Cortisol Bioelectronics Using a Novel Cortisol Antibody

Abstract Cortisol plays an important role as a stress biomarker in human biological fluids, affecting the blood pressure, glucose levels, carbohydrate metabolism, and immune response mechanisms. Increased cortisol levels cause various diseases, including obesity, diabetes, hypertension, chronic fatigue, menstrual irregularity, and increased appetite. Moreover, mental healthcare can be controlled by controlling cortisol levels. Herein, an immuno-graphene field-effect transistor (IGFET) bioelectronic for cortisol detection was developed using a side-gate FET system based on the conjugation of a novel cortisol scFv-Fc antibody (Ab), produced from M13 bacteriophage display method, via oligo(phenylene-ethynylene)amine (OPE) interfacial chemical. The improved performance was obtained from the increased binding affinities between Ab and cortisol and the enhanced carrier mobility via formation of covalent bonds between OPE and graphene, and the IGFET bioelectronics showed excellent sensing performance with a limit of detection of 500 fM, a sensing monitoring range from 500 fM to 100 nM, a rapid detection time of 20 s, and a high-selective detection that enabled the detection of 103 times lower cortisol concentrations than those of interference substances. In addition, the cortisol detection and monitoring were evaluated using artificial sweat, achieving similar performance to that of standard detection monitoring. Based on the results, this IGFET bioelectronics can be utilized to the stress-related assistance indicator and for the rapid observation of changes in cortisol levels.

Ontogenetic features of hormonal status and metabolic profile of pigs in industrial technology

The hormonal and metabolic profile of conditionally healthy Yorkshire pigs of different age and sex groups was studied in an industrial pig farm. A statistically significant effect of age on the level of serum cortisol, triiodothyronine, and thyroxine in the studied pig groups was established. Increased cortisol levels compared to the literature data in almost all pig groups may indicate chronic stress, while increased secretion of thyroid hormones is an adaptive response associated with stress compensation. Biochemical parameters of blood serum in animals of different groups reflect age-related metabolic features. It was shown that the average parameter values for the groups as a whole are within the limits obtained by other authors. It was revealed that with age, there is a decrease in the content of glucose, triglycerides, and urea. At the same time, the level of total protein, albumins, and globulins in the blood serum of the studied pigs gradually increases with age. In some cases, reliable intersexual differences in the level of biochemical parameters were found, in particular, sows exceeded boars in cholesterol content, while the opposite pattern was noted for total protein. In general, the hormonal and metabolic profiles of the herd correspond to the “industrial” status of the complex. The ability to adapt, intensive protein, carbohydrate and fat metabolism are obviously fixed by targeted breed selection. The established reference values of the hormonal status and metabolic profile parameters can be used to characterize pigs of high-intensity meat breeds under industrial technology conditions.

Correlation analyse between thyroid hormone levels and severity of schizophrenia symptoms.

The imbalance of hormone levels in the body is closely related to the occurrence and progression of schizophrenia, especially thyroid hormones. To study the relationship between triiodothyronine (T3), thyroxine (T4), free T3 (FT3), free T4 (FT4), thyroid stimulating hormone (TSH) and schizophrenia. In this study, 100 schizophrenia patients were selected from our hospital between April 2022 and April 2024. Their clinical data were analyzed retrospectively. Based on the Positive and Negative Syndrome Scale (PANSS) score, patients were divided into mild (1-3 points, n = 39), moderate (4 points, n = 45), and severe groups (5-7 points, n = 16). Additionally, 55 healthy individuals served as a control group. Venous blood samples were collected to measure T3, T4, FT3, FT4, TSH, and cortisol concentrations, analyzing their relationship with PANSS scores. The serum levels of T3, FT3, FT4, TSH and cortisol in the schizophrenia group were lower than those in the control group (P < 0.05). With the increase of the severity of the disease, the concentrations of T3 and T4 decreased, while the concentrations of TSH and cortisol increased (P < 0.05). The concentrations of TSH and cortisol were positively correlated with the PANSS score, while T3 and T4 were negatively correlated with the PANSS score (P < 0.05). The receiver operating characteristic curve results showed that T3, T4, TSH, and cortisol had good efficacy in the diagnosis of schizophrenia. Logistic results showed that decreased T3 level, decreased T4 level, decreased TSH level and increased cortisol level may be independent risk factors for schizophrenia. Thyroid hormone levels are associated with the severity of schizophrenia symptoms, which can provide new solutions for the diagnosis and treatment of schizophrenia.

The Complex Relationship between Stress and Gestational Diabetes: Mechanisms and Interventions for Maternal and Fetal Health

Gestational diabetes mellitus (GDM) is a prevalent complication during pregnancy that poses risks to both maternal and fetal health. This study aims to elucidate the intricate relationship between stress and the development of GDM, highlighting how stress-related hormonal fluctuations and behavioral changes—such as increased cortisol levels, inflammation, disrupted sleep patterns, and poor dietary choices— contribute to insulin resistance and glucose dysregulation. We examine the influence of stress on hormonal and lifestyle factors associated with GDM and evaluate interventions that manage stress-related metabolic disturbances. Elevated levels of stress hormones (like cortisol and adrenaline) and inflammatory markers (such as IL-6 and TNF-α) are linked to an increased risk of GDM due to their detrimental effects on insulin sensitivity. Our findings suggest that effective interventions, including mindfulness practices, cognitive-behavioral therapy, and regular physical activity, can reduce cortisol levels and enhance glucose regulation. This underscores the necessity of addressing both the metabolic and psychological dimensions of GDM. Current evidence supports the integration of stress-reduction strategies—such as mindfulness, cognitive-behavioral therapy, and exercise—into GDM management, as they can improve glycemic control by lowering cortisol and enhancing insulin sensitivity. Recognizing stress as a modifiable risk factor for GDM is crucial for improving maternal and fetal outcomes, emphasizing the importance of incorporating stress management into GDM prevention and treatment protocols.

The effect of methylphenidate on the reproductive function of female rats.

Research on the effects of methylphenidate on female fertility is limited. This study evaluated the effects of methylphenidate on reproductive function, oxidants, antioxidants, proinflammatory cytokines, prolactin, and cortisol in female rats. Forty-eight albino Wistar female rats were divided into four groups consisting of 12 rats, which were given pure water orally once daily for 7 days (HG-1), 10 mg/kg methylphenidate orally once daily for 7 days (MP-1), pure water orally once daily for 30 days (HG-2), and 10 mg/kg methylphenidate orally once daily for 30 days (MP-2). At the end of the treatment periods, tail vein blood was collected from six rats per group for prolactin and cortisol determination. Subsequently, euthanasia was performed and the ovaries were removed. Ovaries were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α), and immunohistochemically. For breeding, the remaining six rats were mated with male rats for 1 month. Rats that failed to give birth were classed as infertile. A comparison of MP-1 and MP-2 groups to healthy controls revealed an elevation in MDA and corticosterone levels, and a decline in tGSH, SOD, and CAT levels (p < 0.001). Methylphenidate did not affect prolactin, IL-1β, and TNF-α levels (p > 0.05). MP-1 and MP-2 exhibited immunopositivity for 8-hydroxy-2'-deoxyguanosine (8-OHDG). MP-2 rats developed 66.7% infertility while MP-1, HG-1, and HG-2 rats did not. In ovaries, methylphenidate caused oxidative stress, but did not induce inflammation. Long-term use of methylphenidate caused increased cortisol levels and infertility.

Basal cortisol level modulates stress-induced opioid-seeking behavior

In preclinical studies and our human laboratory, the α2-noradrenergic autoreceptor antagonist yohimbine was found to promote drug-seeking behavior. This study evaluated effects of dose-combinations of yohimbine and the glucocorticoid receptor agonist hydrocortisone to model intensity-dependent effects of stimulating each neurochemical system, alone and together, on stress-reactivity and opioid-seeking. Twelve regular heroin-using participants diagnosed with opioid use disorder (OUD) were stabilized on sublingual buprenorphine (8-mg/day), then passed a hydromorphone 18-mg vs. placebo intramuscular reinforcement screen. Across 9 experimental conditions (3×3 within-subject, randomized crossover, placebo-controlled, double-blind design) during inpatient buprenorphine maintenance, combinations of oral pretreatment doses of yohimbine (0, 27, 54-mg; t=0min) then hydrocortisone (0, 20, 40-mg; t=45min) were administered. In each condition, subjective drug and mood effects, cardiovascular responses, and saliva cortisol and α-amylase levels were assessed to evaluate stress-reactivity, and participants completed a 12-trial choice progressive ratio task during which they could earn units of hydromorphone (1.5-mg intramuscular) and/or money ($2.00). Yohimbine dose-dependently increased blood pressure, α-amylase, and anxiety scores, and decreased opioid agonist symptoms; hydrocortisone dose-dependently increased cortisol levels. Yohimbine/hydrocortisone dose-combinations significantly shifted within-session responding from money to opioid-seeking among participants with lower basal cortisol levels. These findings replicate yohimbine effects on stress biomarkers and demonstrate that noradrenergic/glucocorticoid-potentiated opioid-seeking is modulated by basal cortisol level. In persons with OUD stabilized on buprenorphine, basal HPA-axis activity and acute stressors can enhance opioid relative reinforcing efficacy. These factors may limit OUD treatment efficacy and highlight the need for novel interventions that prevent stress-induced opioid-seeking.

Temperature, dietary lipids, and Aeromonas hydrophila modulate self-protection mechanisms in pacu Piaractus mesopotamicus Holmberg 1887.

Water temperature has a direct influence on several physiological processes in fish. This study investigated the effects of the exposure of pacu (Piaractus mesopotamicus) to 10 days of reduced temperature in stress and innate immune and antioxidant systems, all of which are involved in energy mobilization. Two groups of fish, fed a control diet or a diet with a higher lipid level, were exposed for 10 days to 16°C and then inoculated with Aeromonas hydrophila bacterin. Samples were taken before and after 5 and 10 days of exposure. The results showed that the low temperature (16°C) was a stressor, increasing cortisol levels. Higher levels of cortisol were seen in fish with more body fat, especially at 16°C, compared to those fed control diet. The immune system was enhanced by low temperature that activated the hemolytic activity of the complement system (HAC50) and lysozyme after 10 days of exposure in fish with more body fat. Bacterin inoculation, regardless of temperature and body fat, impaired the respiratory activity of leukocytes, but the complement system activity remained at the levels seen before cold activation. Similarly, lysozyme remained at the levels seen before cold activation, showing later activation. Furthermore, soon after inoculation (at 3 and 6 h), bacterin induced oxidative stress that decreased at 24 h when the concentration of reduced glutathione (GSH) showed lower levels, suggesting that GSH was consumed to attenuate the oxidative stress. Pacu was resilient to the reduced temperature, displaying protective responses to the stressful condition using lipids to modulate these responses.

7469 A Case of Severe Transient Hypercortisolism In a Patient With Bacterial Meningitis

Abstract Disclosure: R. Harxhi: None. D.V. Mihailescu: None. Background: Increased cortisol levels are known to occur in states of significant stress caused by acute illness. This may be attributed to stress leading to a rise in the corticotrophin releasing hormone thereby increasing adrenocorticotrophic hormone levels. This may consequently result in severe transient hypercortisolism and bilateral adrenal structural changes.Clinical case:A 55-year-old female with a past medical history of HTN and pre-diabetes presented to the hospital with a headache and altered mental status starting the day prior to admission. On arrival, she was found to be hypertensive, confused and was diagnosed with acute bacterial meningitis caused by streptococcus pneumoniae. Initial labs were notable for a potassium level of 2.5 mEq/L (normal 3.5-5 mEq/L). Work-up of persistent hypokalemia revealed a cortisol of 54.83 ug/dL (normal 6.7-22.6 ug/dL), ACTH 166 pg/mL (normal 9-50 pg/mL), aldosterone &amp;lt; 1 ng/dL (normal 3-16 ng/dL), and renin 0.57 (normal 0.25-5.82). CT of the abdomen showed bilateral periadrenal fat stranding, larger on the left with no adrenal nodules. On physical exam, patient did not exhibit any cushingoid features. Significantly elevated AM cortisol levels persisted despite treatment with high dose dexamethasone as part of the meningitis regimen (20 mg) resulting in unsuppressed AM cortisol of 9.22 ug/dL. An MRI of the brain showed a partially empty sella rendering a pituitary adenoma unlikely. Patient’s clinical status improved rapidly, and hypokalemia resolved. A low dose dexamethasone suppression test performed 9 days post admission produced an appropriately suppressed cortisol (1.0 ug/dL) and ACTH (14 pg/mL) levels, thus confirming a functional response to acute illness. Conclusion: This is a rare case of severe transient hypercortisolism with periadrenal congestion (“fat stranding”) resulting in hypokalemia (likely due inappropriate activation of mineralocorticoid receptors) in the setting of acute illness. There have been a very limited number of similar cases reported in literature, particularly with respect to CNS infections. It is important to recognize the response to acute stress could produce significant elevation of cortisol levels leading to the activation of mineralocorticoid receptors, therefore mimicking primary hyperaldosteronism. Presentation: 6/1/2024

7990 Reduced Alpha-1 Antitrypsin Activity Is Associated with Higher Plasma Free Cortisol and Increased Tissue Glucocorticoid Exposure in Humans in vivo

Abstract Disclosure: L.D. Boyle: None. M. Nixon: None. C.M. Underhill: None. L.A. Hill: None. N.Z. Homer: None. M. Magennis: None. R. Andrew: None. G.L. Hammond: None. J.G. Lewis: None. R.H. Stimson: None. B.R. Walker: None. Background: Corticosteroid Binding Globulin (CBG) binds &amp;gt;85% of plasma cortisol, modulating its biological activity. Proteolytic cleavage by neutrophil elastase (NE) reduces CBG binding capacity, proposed to increase free cortisol availability to inflamed tissues. Genetic variation at the locus spanning SERPINA1 (encoding alpha-1 antitrypsin, AAT, the endogenous inhibitor of NE) and SERPINA6 (CBG) altered morning total plasma cortisol. We hypothesised that AAT deficiency increased CBG cleavage and hence free plasma cortisol, resulting in amplified tissue cortisol delivery and increased HPA axis negative feedback. We tested this in recall-by-genotype studies of people who are heterozygous for inactivating mutations in SERPINA1. Methods: 16 asymptomatic carriers of deleterious SERPINA1 single nucleotide polymorphisms (rs17580 &amp; rs28929474) and 16 age-, gender- and BMI-matched controls were recruited from the Generation Scotland Biobank. To quantify in vivo whole body glucocorticoid appearance and clearance rates, and estimate tissue cortisol uptake, we performed arterio-venous plasma sampling across abdominal adipose and skeletal muscle during steady-state 9,11,12,12-[2H]4-cortisol tracer infusion. To assess endogenous negative feedback, participants underwent combined receptor antagonist stimulation of the HPA axis (‘CRASH’) testing using RU486 and spironolactone, or placebo in a double blind randomised crossover design. Total cortisol (LC-MS/MS), free cortisol (isotopic dilution &amp; ultrafiltration), CBG binding capacity (radioligand displacement), CBG concentration and AAT (ELISA) were measured in plasma. Tissue cortisol (LC-MS/MS) and glucocorticoid-dependent transcripts (qPCR) were measured in adipose biopsy samples collected at end of study. Results: AAT was ∼30% lower in AAT+/- (p=0.0002 vs control). Plasma CBG concentration, binding capacity and total cortisol were similar between groups. However, plasma free cortisol fraction was higher in AAT+/- subjects (16.1 +/- 0.2 vs 13.9 +/- 0.04 %, p&amp;lt;0.0001). Adipose tissue from AAT+/- subjects displayed increased cortisol levels and increased glucocorticoid-responsive transcripts PER1 and LPL compared to controls. Consistent with release from CBG, total and free cortisol release across skeletal muscle was increased in AAT+/- subjects vs controls. The rate of appearance of 9,12,12-[2H]3-cortisol was reduced in AAT+/- (p=0.03 vs control), consistent with decreased whole body 11β-HSD1 activity. CRASH testing did not reveal additional differences between groups. Discussion: Subclinical AAT deficiency is associated with a higher free cortisol fraction and increased tissue glucocorticoid exposure. Although consistent with the hypothesis of local tissue-mediated control of glucocorticoid exposure via the NE/AAT/CBG axis, these findings were not accompanied by measurable changes in CBG. Presentation: 6/3/2024

9225 Reduced Alpha-1 Antitrypsin Activity Is Associated with Higher Plasma Free Cortisol and Increased Tissue Glucocorticoid Exposure in Humans in vivo

Abstract Disclosure: L.D. Boyle: None. M. Nixon: None. C.M. Underhill: None. L.A. Hill: None. N.Z. Homer: None. M. Magennis: None. R. Andrew: None. G.L. Hammond: None. J.G. Lewis: None. R.H. Stimson: None. B.R. Walker: None. Background Corticosteroid Binding Globulin (CBG) binds &amp;gt;85% of plasma cortisol, modulating its biological activity. Proteolytic cleavage by neutrophil elastase (NE) reduces CBG binding capacity, proposed to increase free cortisol availability to inflamed tissues. Genetic variation at the locus spanning SERPINA1 (encoding alpha-1 antitrypsin, AAT, the endogenous inhibitor of NE) and SERPINA6 (CBG) altered morning total plasma cortisol. We hypothesised that AAT deficiency increased CBG cleavage and hence free plasma cortisol, resulting in amplified tissue cortisol delivery and increased HPA axis negative feedback. We tested this in recall-by-genotype studies of people who are heterozygous for inactivating mutations in SERPINA1. Methods 16 asymptomatic carriers of deleterious SERPINA1 single nucleotide polymorphisms (rs17580 &amp; rs28929474) and 16 age-, gender- and BMI-matched controls were recruited from the Generation Scotland Biobank. To quantify in vivo whole body glucocorticoid appearance and clearance rates, and estimate tissue cortisol uptake, we performed arterio-venous plasma sampling across abdominal adipose and skeletal muscle during steady-state 9,11,12,12-[2H]4-cortisol tracer infusion. To assess endogenous negative feedback, participants underwent combined receptor antagonist stimulation of the HPA axis (‘CRASH’) testing using RU486 and spironolactone, or placebo in a double blind randomised crossover design. Total cortisol (LC-MS/MS), free cortisol (isotopic dilution &amp; ultrafiltration), CBG binding capacity (radioligand displacement), CBG concentration and AAT (ELISA) were measured in plasma. Tissue cortisol (LC-MS/MS) and glucocorticoid-dependent transcripts (qPCR) were measured in adipose biopsy samples collected at end of study. Results AAT was ∼30% lower in AAT+/- (p=0.0002 vs control). Plasma CBG concentration, binding capacity and total cortisol were similar between groups. However, plasma free cortisol fraction was higher in AAT+/- subjects (16.1 +/- 0.2 vs 13.9 +/- 0.04 %, p&amp;lt;0.0001). Adipose tissue from AAT+/- subjects displayed increased cortisol levels and increased glucocorticoid-responsive transcripts PER1 and LPL compared to controls. Consistent with release from CBG, total and free cortisol release across skeletal muscle was increased in AAT+/- subjects vs controls. The rate of appearance of 9,12,12-[2H]3-cortisol was reduced in AAT+/- (p=0.03 vs control), consistent with decreased whole body 11β-HSD1 activity. CRASH testing did not reveal additional differences between groups. Discussion Subclinical AAT deficiency is associated with a higher free cortisol fraction and increased tissue glucocorticoid exposure. Although consistent with the hypothesis of local tissue-mediated control of glucocorticoid exposure via the NE/AAT/CBG axis, these findings were not accompanied by measurable changes in CBG. Presentation: 6/3/2024

5164 Long COVID patients with menstrual symptoms: a retrospective study in Japan

Abstract Disclosure: F. Otsuka: None. Y. Sakurada: None. Y. Matsuda: None. T. Hasegawa: None. Y. Otsuka: None. Y. Nakano: None. K. Tokumasu: None. K. Yamamoto: None. N. Sunada: None. H. Honda: None. H. Hagiya: None. K. Ueda: None. It has been recognized that about one third of patients may suffer from prolonged illness after surviving from the acute phase of COVID-19. Various symptoms of the prolonged illness have been evaluated by many institutions including WHO. However, the mechanisms of the prolonged symptoms have yet to be elucidated. Long COVID is a complicated illness that develops after SARS-CoV-2 infection, independent of the severity of COVID-19. Long COVID is defined as symptoms that occur within 3 months after the initial infection and persist for at least 2 months. The major symptoms of long COVID include general fatigue, post-exertional malaise, headache, insomnia, dyspnea, cognitive dysfunction, low-grade fever, and muscle pain. Proposed pathophysiological mechanisms of long COVID include pathogen persistence and viral reactivation, immune dysregulation and autoimmunity, neurological abnormalities, tissue damage due to hypoperfusion and/or microclots, autonomic and endocrine dysfunctions, and dysregulation of microbiomes. In the present study, we aimed to elucidate the impact of long COVID on female reproductive health. In this retrospective study, medical records of patients who visited our long COVID clinic and clinical trends of their menstrual symptoms were evaluated. In our study, of 349 female patients who visited our clinic between Feb 2021 and Mar 2023, 223 patients with long COVID (18-50 years) were included. It was revealed that 44 females (19.7%) had menstrual symptoms associated with long COVID. The patients with menstrual symptoms were significantly older than those without menstrual symptoms (42.5 vs. 38 years). The percentage of patients with menstrual symptoms was higher during the Omicron phase (24%) than during the Preceding (13%) and Delta (12%) phases. Cycle irregularity (63.6%) was the most frequent menstrual symptom, followed by severe pain (25%), heavy bleeding (20.5%), perimenopausal symptoms (18.2%), and premenstrual syndrome (15.9%). Fatigue and depression were the most frequent complications with menstrual complaints. Scores indicating fatigue and QOL were significantly worse in long COVID patients with menstrual symptoms. Endocrine examinations showed significantly increased cortisol levels in patients with menstrual complaints although plasma adrenocorticotropin levels were not altered. Hence, long COVID has an impact on women’s reproductive and mental health. Presentation: 6/1/2024

5164 Long COVID patients with menstrual symptoms: a retrospective study in Japan

Abstract Disclosure: F. Otsuka: None. Y. Sakurada: None. Y. Matsuda: None. T. Hasegawa: None. Y. Otsuka: None. Y. Nakano: None. K. Tokumasu: None. K. Yamamoto: None. N. Sunada: None. H. Honda: None. H. Hagiya: None. K. Ueda: None. It has been recognized that about one third of patients may suffer from prolonged illness after surviving from the acute phase of COVID-19. Various symptoms of the prolonged illness have been evaluated by many institutions including WHO. However, the mechanisms of the prolonged symptoms have yet to be elucidated. Long COVID is a complicated illness that develops after SARS-CoV-2 infection, independent of the severity of COVID-19. Long COVID is defined as symptoms that occur within 3 months after the initial infection and persist for at least 2 months. The major symptoms of long COVID include general fatigue, post-exertional malaise, headache, insomnia, dyspnea, cognitive dysfunction, low-grade fever, and muscle pain. Proposed pathophysiological mechanisms of long COVID include pathogen persistence and viral reactivation, immune dysregulation and autoimmunity, neurological abnormalities, tissue damage due to hypoperfusion and/or microclots, autonomic and endocrine dysfunctions, and dysregulation of microbiomes. In the present study, we aimed to elucidate the impact of long COVID on female reproductive health. In this retrospective study, medical records of patients who visited our long COVID clinic and clinical trends of their menstrual symptoms were evaluated. In our study, of 349 female patients who visited our clinic between Feb 2021 and Mar 2023, 223 patients with long COVID (18-50 years) were included. It was revealed that 44 females (19.7%) had menstrual symptoms associated with long COVID. The patients with menstrual symptoms were significantly older than those without menstrual symptoms (42.5 vs. 38 years). The percentage of patients with menstrual symptoms was higher during the Omicron phase (24%) than during the Preceding (13%) and Delta (12%) phases. Cycle irregularity (63.6%) was the most frequent menstrual symptom, followed by severe pain (25%), heavy bleeding (20.5%), perimenopausal symptoms (18.2%), and premenstrual syndrome (15.9%). Fatigue and depression were the most frequent complications with menstrual complaints. Scores indicating fatigue and QOL were significantly worse in long COVID patients with menstrual symptoms. Endocrine examinations showed significantly increased cortisol levels in patients with menstrual complaints although plasma adrenocorticotropin levels were not altered. Hence, long COVID has an impact on women’s reproductive and mental health. Presentation: 6/1/2024

Systemic immunostimulation induces glucocorticoid-mediated thymic involution succeeded by rebound hyperplasia which is impaired in aged recipients.

The thymus is the central organ involved with T-cell development and the production of naïve T cells. During normal aging, the thymus undergoes marked involution, reducing naïve T-cell output and resulting in a predominance of long-lived memory T cells in the periphery. Outside of aging, systemic stress responses that induce corticosteroids (CS), or other insults such as radiation exposure, induce thymocyte apoptosis, resulting in a transient acute thymic involution with subsequent recovery occurring after cessation of the stimulus. Despite the increasing utilization of immunostimulatory regimens in cancer, effects on the thymus and naïve T cell output have not been well characterized. Using both mouse and human systems, the thymic effects of systemic immunostimulatory regimens, such as high dose IL-2 (HD IL-2) with or without agonistic anti-CD40 mAbs and acute primary viral infection, were investigated. These regimens produced a marked acute thymic involution in mice, which correlated with elevated serum glucocorticoid levels and a diminishment of naïve T cells in the periphery. This effect was transient and followed with a rapid thymic "rebound" effect, in which an even greater quantity of thymocytes was observed compared to controls. Similar results were observed in humans, as patients receiving HD IL-2 treatment for cancer demonstrated significantly increased cortisol levels, accompanied by decreased peripheral blood naïve T cells and reduced T-cell receptor excision circles (TRECs), a marker indicative of recent thymic emigrants. Mice adrenalectomized prior to receiving immunotherapy or viral infection demonstrated protection from this glucocorticoid-mediated thymic involution, despite experiencing a substantially higher inflammatory cytokine response and increased immunopathology. Investigation into the effects of immunostimulation on middle aged (7-12 months) and advance aged (22-24 months) mice, which had already undergone significant thymic involution and had a diminished naïve T cell population in the periphery at baseline, revealed that even further involution was incurred. Thymic rebound hyperplasia, however, only occurred in young and middle-aged recipients, while advance aged not only lacked this rebound hyperplasia, but were entirely absent of any indication of thymic restoration. This coincided with prolonged deficits in naïve T cell numbers in advanced aged recipients, further skewing the already memory dominant T cell pool. These results demonstrate that, in both mice and humans, systemic immunostimulatory cancer therapies, as well as immune challenges like subacute viral infections, have the potential to induce profound, but transient, glucocorticoid-mediated thymic involution and substantially reduced thymic output, resulting in the reduction of peripheral naive T cells. This can then be followed by a marked rebound effect with naïve T cell restoration, events that were shown not to occur in advanced-aged mice.

Psychosomatics: Communication of the Central Nervous System through Connection to Tissues, Organs, and Cells.

This study aimed to scrutinize existing evidence concerning the link between somatic symptoms and nervous system activity. The goal was to pinpoint areas for effective therapeutic interventions. Psychosomatic disorders, an often overlooked field of medicine, bears significance given the multitude of patients experiencing somatic symptoms due to specific emotions and experiences. The literature was explored using the methods of comparative analysis, synthesis and graphical representation. The study introduced pathological neural networks localized in brain regions such as the prefrontal cortex and hippocampus, leading to maladaptive behaviors and heightened negative focus. Activation of the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis, alongside increased cortisol levels, induces chronic distress, inflammation, and disruptions in neurotransmitter metabolism. The gut microbiota significantly influences psychosomatic reactions. Patients with psychosomatic disorders require complex treatment with cognitive-behavioural therapy and hypnosis methods. Within the framework of pathological neural networks, the MindChat technique has yielded effectiveness with the purpose of "dehypnotization" and destruction of aberrant cognitive and emotional patterns. However, it should be noted that this technique requires further empirical support.

Hypothalamic-pituitary-adrenal axis functioning in offspring of parents with a major affective disorder: a meta-analytic review.

Because the offspring of parents with an affective disorder (OAD) are at high risk for developing mental disorders, and persons with an affective disorder (AD) show dysfunctional hypothalamic-pituitary-adrenal (HPA) axis activity, changes in HPA functioning in OAD might be an etiological risk factor that precedes the development of ADs. The primary aim of the meta-analysis was to quantitatively summarize the existing data on different indices of diurnal cortisol in the OAD. The secondary aim was to explore potential moderators of this relation. Following PRISMA guidelines, we included 26 studies (3052 offspring) on diurnal cortisol in our meta-analysis after an initial screening of 3408 articles. Intercept-only and meta-regression models were computed using the robust variance estimation method. Analyses examining mean cortisol levels at discrete timepoints, total cortisol output, and the cortisol rise in response to awakening (CAR) were conducted separately. The results demonstrated that the OAD had higher mean levels of cortisol at different timepoints throughout the day compared to controls (Hedge's g = 0.21). There was evidence of publication bias in studies examining CAR, such that effect sizes were positively biased. The present findings are consistent with a meta-analysis showing elevated cortisol in youth having an AD. Notable limitations across studies include the method of cortisol measurement and assessment of ADs. Altogether, these results highlight the fact that increased cortisol levels may act as a potential neuroendocrine antecedent and/or risk factor for the development of ADs among high risk youth.

A systematic review and meta-analysis of cortisol levels in Plasmodium infections

Malaria has complex interactions with host physiology, including alterations in cortisol levels. Cortisol, a key hormone in the stress response, is known to be dysregulated in various infectious diseases. This systematic review and meta-analysis aimed to elucidate the relationship between Plasmodium infection and cortisol levels, shedding light on the intricate interplay between the parasite and the host’s endocrine system. The methodological protocol for assessing cortisol levels in malaria patients was registered in PROSPERO (CRD42024496578), a widely recognized international prospective register of systematic reviews. This registration ensures transparency and minimizes the risk of bias in our research. A comprehensive search strategy was employed across major databases, including Embase, PubMed, Scopus, and Medline, to include studies that reported cortisol levels in infected patients. The qualitative synthesis was undertaken to synthesize the difference in cortisol levels between malaria-infected and uninfected individuals. The meta-analysis employed the random effects model in the quantitative synthesis to calculate the effect estimate. The review included a total of 20 studies, with a substantial number conducted in Africa, followed by Asia and South America. Most included studies (13/20, 65%) reported higher cortisol levels in infected patients than in uninfected patients. The meta-analysis confirmed significantly higher cortisol levels in infected patients compared to uninfected individuals (P < 0.0001, standardized mean difference (SMD): 1.354, 95% confidence interval: 0.913 to 1.795, I2: 88.3%, across 15 studies). Notably, the method for cortisol measurement and the type of blood sample used (serum or plasma) were significant moderators in the analysis, indicating that these factors may influence the observed relationship between Plasmodium infection and cortisol levels. The systematic review and meta-analysis confirmed that Plasmodium infection is associated with increased cortisol levels, highlighting the intricate relationship between the disease and the host stress response. These findings underscore the potential of cortisol as a supplementary biomarker for understanding the pathophysiological impact of malaria. By providing insights into the stress-related mechanisms of malaria, this comprehensive understanding can inform future research and potentially enhance disease management and treatment strategies, particularly in regions heavily burdened by malaria.

Anticipated stress predicts the cortisol awakening response: An intensive longitudinal pilot study

The cortisol awakening response (CAR) has been hypothesized to prepare the body for anticipated demands of the upcoming day. This pilot study investigates the influence of anticipated stress on the upcoming day on the CAR, using an intensive longitudinal design with ecological momentary assessments. Over a 30-day period, three healthy participants collected saliva samples each morning at three time points after awakening to measure cortisol levels and completed a questionnaire each evening on the anticipated stress for the following day. Additionally, they wore a smart headband to objectively determine the time point of awakening. There was high variability in the CAR magnitude within participants over time. A multi-level model was estimated to investigate the influence of anticipated stress on the CAR. Results indicated that anticipated stress is predictive of the CAR on the following morning, with higher anticipated stress being associated with increased cortisol levels at the post-awakening time points. These findings underscore the role of stress anticipation in modulating the CAR and highlight the importance of considering within-person variation and temporally lagged effects in biopsychological research.

Longitudinal analysis of cortisol changes during pubertal development in indigenous Qom girls.

Pubertal research has primarily focused on hypothalamic-pituitary-gonadal axis (HPG) regulation of puberty, though the hypothalamic-pituitary-adrenal axis (HPA) is increasingly considered critical. Heightened HPA function proxied by increasing cortisol levels may play a role in accelerated pubertal timing. However, the extent to which cortisol varies across ages and its relation to pubertal changes in linear growth are less well substantiated. We explored relationships between age, linear growth, adiposity, C-peptide (proxy for insulin), and cortisol across puberty, and we tested whether higher cortisol levels are associated with earlier ages at menarche and peak height velocity. We utilize longitudinal data (n = 777 urine samples) from Qom females ages 7-14 (n = 46) and test our pre-registered analysis using Bayesian longitudinal mixed effects models and joint modeling techniques. We find limited evidence supporting the overarching hypothesis that HPA upregulation is associated with pubertal maturation or timing. We find some evidence that HPA upregulation, as proxied by cortisol, may be more clearly related to differences in relative linear growth at early-mid puberty, as measured by height-for-age z-scores. Transdisciplinary perspectives on puberty, including the assumption that stressors acting via cortisol accelerate pubertal development, are discussed.

Biochemical Changes in Adult Male Gamers During Prolonged Gaming: Pilot Study.

Gaming has become an integrated part of life for children and adults worldwide. Previous studies on the impact of gaming on biochemical parameters have primarily addressed the acute effects of gaming. The literature is limited, and the study designs are very diverse. The parameters that have been investigated most thoroughly are blood glucose and cortisol. This exploratory study is the first to investigate the effects of long gaming sessions on the biochemical parameters of healthy male adults. The extensive testing allowed us to observe short-term changes (within 6 hours), long-term changes during the duration of the gaming sessions, and follow-up after 1 week to determine whether any changes were longer lasting. In total, 9 experienced gamers completed 2 back-to-back 18-hour gaming sessions interspersed with a 6-hour rest period. All participants adhered to a structured sleep pattern due to daytime employment or attending university. Blood, saliva, and urine samples were collected from the participants every 6 hours. Linear mixed-effect models were used to analyze the repeated-measures data accumulated during the study. A total of 51 biochemical parameters were investigated. In total, 12 of the 51 biochemical parameters significantly changed during the study: alkaline phosphatase, aspartate aminotransferase, bilirubin, chloride, creatinine, glucose, hemoglobin, immature reticulocyte fraction, lactate, methemoglobin, sodium, and thrombocytes. All changes were within the normal range. The mean glucose level of the participants was 4.39 (SD 0.07) mmol/L at baseline, which increased significantly by 0.24 (SD 0.07) mmol/L per 6 hours during the first period and by 0.38 (SD 0.07) mmol/L per 6 hours in the second period (P<.001). The glucose levels during the second session increased even though the participants had little energy intake. Cortisol levels did not change significantly, although the cortisol pattern deviated from the typical circadian rhythm. During both gaming sessions, we observed increasing cortisol levels from 6 AM until noon. The participants were relatively dehydrated at the start of the study. The patients were asked to fast before the first blood sampling. Within the first 6 hours of the study, the participants rehydrated, followed by relative dehydration during the remainder of the study. This pattern was identified using the following parameters: albumin, creatinine, hemoglobin, erythrocytes, potassium, and platelets. This study is the first of its kind, and many of the analyses in the study yielded novel results. The study was designed to emulate the behavior of gamers during the weekend and other long gaming sessions. At this point, we are not able to determine the difference between the effects of gaming and behavior during gaming. Regardless, the results of this study suggest that healthy gamers can partake in long gaming sessions, with ample amounts of unhealthy foods and little rest, without acute impacts on health.

Effects of chronic intermittent cold stress on anxiety-depression-like behaviors in adolescent rats

Stress, which triggers numerous physiological and behavioral responses in the organism, is a significant risk factor that contributes to the development of psychiatric disorders such as depression and anxiety. This study aimed to investigate the inflammation, oxidative stress status, anxiety, and depression-like behaviors of adolescent rodents exposed to chronic intermittent cold stress. Adolescent male rats were subjected to a modified chronic intermittent cold stress model (21 days, 1 hour/day, 4 °C). Depression-like behaviors were evaluated using the sucrose preference and forced swimming tests, while anxiety-like behaviors were assessed using the open field, elevated plus maze, and light-dark box tests. We measured levels of cortisol, tumor necrosis factor-α, interleukin-1β, brain-derived natriuretic factor, reactive oxygen species, malondialdehyde, total oxidants and antioxidants, and other chemicals in the prefrontal cortex, thalamus, striatum, and hippocampus brain regions of rats using ELISA and colorimetric methods. Data were analyzed using Student's t-test and Pearson correlation analysis. After the cold stress treatment, both anxiety and depression-like behaviors increased remarkably in the subjects. Our study revealed significant changes in various brain regions among the stress-exposed subjects. Cold stress resulted in decreased BDNF levels in the prefrontal cortex and striatum (p < 0.05), increased cortisol levels in the prefrontal cortex (p < 0.05), increased IL-1β levels in the hippocampus and thalamus (p < 0.05), increased protein carbonyl levels in the striatum (p < 0.05), and decreased TAS in the prefrontal cortex and thalamus (p < 0.05). Adolescent rats exposed to cold exhibit both anxiety- and depression-like behaviors. This study observed an increase in inflammation in various brain regions, yet the responses to stress varied. Our findings suggest that adolescence is a period of heightened sensitivity to stress, which can lead to dramatic consequences.