Abnormal Autonomic Nervous Regulation in Patients with Globus Pharyngeus.

BACKGROUND: Globus pharyngeus could be described as a benign sensation of lump or foreign object in the throat. The etiology of the globus as a solitary syndrome is still unknown, but it is proposed that stress could have an important role in symptom emergence. AIMS: To evaluate the autonomic nervous regulation in patients with globus compared to healthy controls in reaction to stress. METHODS: Patients included in the study were diagnosed based on ROME IV criteria for Disorders of Gut Brain Interaction. Besides globus, the patients did not suffer any other substantial medical condition. As a control group, measurement of healthy volunteers was performed. Both groups underwent the same stress protocol assessment in the same laboratory settings. The protocol consist of two types of stressors: cold pressor test and mental arithmetic test to test different types of autonomic reactivity. RESULTS: Baroreflex sensitivity was significantly decreased in patients compared to controls in all phases of the protocol. Low-frequency band of systolic blood pressure variability was significantly increased during both stress phases in patients compared to controls. High-frequency band of heart rate variability was significantly decreased in patients compared to controls during the both of the stress phases. CONCLUSION: The results of this study shows discrete abnormalities in complex autonomic reflex control which are predominantly manifested in response to stressful stimuli indicating altered neurocardiac regulation as a reaction to stress associated with globus pharynegus. This fact could have an important role in the personalized management of globus patients such as biofeedback.

Mechanisms Involved in the Link between Depression, Antidepressant Treatment, and Associated Weight Change.

Major depressive disorder is a severe mood disorder associated with a marked decrease in quality of life and social functioning, accompanied by a risk of suicidal behavior. Therefore, seeking out and adhering to effective treatment is of great personal and society-wide importance. Weight changes associated with antidepressant therapy are often cited as the reason for treatment withdrawal and thus are an important topic of interest. There indeed exists a significant mechanistic overlap between depression, antidepressant treatment, and the regulation of appetite and body weight. The suggested pathomechanisms include the abnormal functioning of the homeostatic (mostly humoral) and hedonic (mostly dopaminergic) circuits of appetite regulation, as well as causing neuromorphological and neurophysiological changes underlying the development of depressive disorder. However, this issue is still extensively discussed. This review aims to summarize mechanisms linked to depression and antidepressant therapy in the context of weight change.

COVID-19 pandemic as a huge stressor of the 21st century.

The coronavirus disease 2019 (COVID-19) pandemic had a significant impact on the somatic and psychological state of the population worldwide, leading to a wide range of health complications. Most of the studies on the COVID-19 pandemic have focused on the direct psychological and somatic aspects of the disease. However, the negative consequences of the indirect aspect of the pandemic (i.e., stay-at-home orders leading to social isolation) represent a major stressor on psychosomatic health and warrant greater interest. This study examines the COVID-19 pandemic as a significant stressor of the 21st century through the lens of the "allostatic" stress response concept and highlights the stress-related psychosomatic consequences of the COVID-19 pandemic. A better understanding of the pathomechanisms underlying indirect impacts of the pandemic on psychosomatic health can contribute to the implementation of personalized interventions for managing stress responses, thereby reducing the pandemic-linked stress burden and preventing stress-associated disease emergence (Tab. 1, Fig. 1, Ref. 67). Text in PDF www.elis.sk Keywords: COVID-19 pandemic, social isolation, stress response, allostasis, allostatic load, psychosomatic symptoms.

Peripheral Inflammatory Markers in Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder at Adolescent Age.

Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are associated with immune dysregulation. We aimed to estimate the pro- and anti-inflammatory activity/balance in ASD and ADHD patients at a little-studied adolescent age with respect to sex. We evaluated 20 ASD patients (5 girls, average age: 12.4 ± 1.9 y), 20 ADHD patients (5 girls, average age: 13.4 ± 1.8 y), and 20 age- and gender-matched controls (average age: 13.2 ± 1.9 y). The evaluated parameters included (1) white blood cells (WBCs), neutrophils, monocytes, lymphocytes, platelets, platelet distribution width (PDW), mean platelet volume, and derived ratios, as well as (2) cytokines-interferon-gamma, interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, and IL-10, tumor necrosis factor-alpha (TNF-α), and derived profiles and ratios. ASD adolescents showed higher levels of WBC, monocytes, IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, and IL-10, macrophages (M)1 profile, and anti-inflammatory profile than the controls, with ASD males showing higher monocytes, IL-6 and IL-10, anti-inflammatory profile, and a lower T-helper (Th)1/Th2+T-regulatory cell ratio than control males. The ADHD adolescents showed higher levels of PDW, IL-1ß and IL-6, TNF-α, M1 profile, proinflammatory profile, and pro-/anti-inflammatory ratio than the controls, with ADHD females showing a higher TNF-α and pro-/anti-inflammatory ratio than the control females and ADHD males showing higher levels of IL-1ß and IL-6, TNF-α, and M1 profile than the control males. Immune dysregulation appeared to be different for both neurodevelopmental disorders in adolescence.

Electrodermal activity spectral and nonlinear analysis - potential biomarkers for sympathetic dysregulation in autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by emotional and social deficits, which can be associated with sympathetic dysregulation. Thus, we aimed to analyze the electrodermal activity (EDA) using time, and novel spectral and nonlinear indices in ASD. The cohort consisted of 45 ASD boys and 45 age-matched controls. EDA was continuously recorded at rest. The EDA indices were evaluated by time-, spectral-, and nonlinear-domain analysis. Our results revealed increased non-specific skin conductance responses, spectral parameters in high and very-high frequency bands, approximate and symbolic information entropy indicating sympathetic overactivity in ASD vs. controls (p < 0.05, for all). Surprisingly, the nonlinear index from detrended fluctuation analysis α1 was lower in ASD vs. controls (p = 0.024) providing thus distinct information about qualitative features of complex sympathetic regulation. Concluding, the complex time, spectral, and nonlinear EDA indices revealed discrete abnormalities in sympathetic cholinergic regulation as one of the potential pathomechanisms contributing to cardiovascular complications in ASD.

Entropy Analysis of Neonatal Electrodermal Activity during the First Three Days after Birth.

The entropy-based parameters determined from the electrodermal activity (EDA) biosignal evaluate the complexity within the activity of the sympathetic cholinergic system. We focused on the evaluation of the complex sympathetic cholinergic regulation by assessing EDA using conventional indices (skin conductance level (SCL), non-specific skin conductance responses, spectral EDA indices), and entropy-based parameters (approximate, sample, fuzzy, permutation, Shannon, and symbolic information entropies) in newborns during the first three days of postnatal life. The studied group consisted of 50 healthy newborns (21 boys, average gestational age: 39.0 ± 0.2 weeks). EDA was recorded continuously from the feet at rest for three periods (the first day-2 h after birth, the second day-24 h after birth, and the third day-72 h after birth). Our results revealed higher SCL, spectral EDA index in a very-low frequency band, approximate, sample, fuzzy, and permutation entropy during the first compared to second and third days, while Shannon and symbolic information entropies were lower during the first day compared to other periods. In conclusion, EDA parameters seem to be sensitive in the detection of the sympathetic regulation changes in early postnatal life and which can represent an important step towards a non-invasive early diagnosis of the pathological states linked to autonomic dysmaturation in newborns.

Role of Neuroendocrine, Immune, and Autonomic Nervous System in Anorexia Nervosa-Linked Cardiovascular Diseases.

Anorexia nervosa represents a severe mental disorder associated with food avoidance and malnutrition. In patients suffering from anorexia nervosa, cardiovascular complications are the main reason leading to morbidity and mortality. However, the origin and pathological mechanisms leading to higher cardiovascular risk in anorexia nervosa are still unclear. In this aspect, the issue of exact pathological mechanisms as well as sensitive biomarkers for detection of anorexia nervosa-linked cardiovascular risk are discussed. Therefore, this review synthesised recent evidence of dysfunction in multiple neuroendocrine axes and alterations in the immune system that may represent anorexia nervosa-linked pathological mechanisms contributing to complex cardiovascular dysregulation. Further, this review is focused on identification of non-invasive biomarkers for the assessment of increased cardiovascular risk in anorexia nervosa that can be linked to a clinical application. Complex non-invasive assessment of cardiovascular autonomic regulation-cardiac vagal control (heart rate variability), sympathetic vascular activity (blood pressure variability), and cardiovascular reflex control (baroreflex sensitivity)-could represent a promising tool for early diagnosis, personalized therapy, and monitoring of therapeutic interventions in anorexia nervosa particularly at a vulnerable adolescent age.

Novel Insight into Neuroimmune Regulatory Mechanisms and Biomarkers Linking Major Depression and Vascular Diseases: The Dilemma Continues.

Major depressive disorder (MDD) represents a serious health problem estimated to affect 350 million people globally. Importantly, MDD has repeatedly emerged as an etiological or prognostic factor in cardiovascular disease (CVD) development, including vascular pathology. Several linking pathomechanisms between MDD and CVD involve abnormal autonomic regulation, inflammation, and endothelial dysfunction as an early preclinical stage of atherosclerosis. However, the cause of accelerated atherosclerosis in MDD patients remains unclear. Recently, the causal relationships between MDD and mediator (e.g., inflammation and/or endothelial dysfunction), as well as the causal pathways from the mediator to atherosclerosis, were discussed. Specifically, MDD is accompanied by immune dysregulation, resulting in increased production of proinflammatory cytokines (e.g., interleukin (IL)-6 and tumor necrosis factor (TNF)-α), which could lead to depression-linked abnormalities in brain function. Further, MDD has an adverse effect on endothelial function; for example, circulating markers of endothelial dysfunction (e.g., soluble adhesion molecules, von Willebrand factor) have been linked with depression. Additionally, MDD-linked autonomic dysregulation, which is characterized by disrupted sympathovagal balance associated with excessive circulating catecholamines, can contribute to CVD. Taken together, activated inflammatory response, endothelial dysfunction, and autonomic dysregulation could affect gradual atherosclerosis progression, resulting in a higher risk of developing CVD in MDD. This review focused on the pathomechanisms linking MDD and CVD with respect to neuroimmune regulation, and the description of promising biomarkers, which is important for the early diagnosis and personalized prevention of CVD in major depression.

Novel Biomarkers of Early Atherosclerotic Changes for Personalised Prevention of Cardiovascular Disease in Cervical Cancer and Human Papillomavirus Infection.

Cervical cancer is associated with a causative role of human papillomavirus (HPV), which is a highly prevalent infection. Recently, women with a genital HPV infection were found to have increased incidence of cardiovascular diseases (CVD), including severe cardiovascular events such as myocardial infarction and stroke. The pathomechanisms of this relation are not yet fully understood, and may significantly affect the health of a large part of the population. Accelerated atherosclerosis is assumed to play a key role in the pathophysiology of this relationship. To identify high-risk groups of the population, it is necessary to stratify the CVD risk. Current algorithms, as widely used for the estimation of CVD risk, seem to be limited by the individual misclassification of high-risk subjects. However, personalised prediction of cardiovascular events is missing. Regarding HPV-related CVD, identification of novel sensitive biomarkers reflecting early atherosclerotic changes could be of major importance for such personalised cardiovascular risk prediction. Therefore, this review focuses on the pathomechanisms leading to HPV-related cardiovascular diseases with respect to atherosclerosis, and the description of potential novel biomarkers to detect the earliest atherosclerotic changes important for the prevention of CVD in HPV infection and cervical cancer.

Endothelial function in children with white-coat hypertension.

Several studies have demonstrated endothelial dysfunction in patients with essential hypertension. However, the presence of endothelial dysfunction in children with white-coat hypertension has not been studied. We evaluated the endothelial function in children with white-coat hypertension and essential hypertension using a novel method based on the assessment of flow-mediated dilation (FMD). Study involved 106 children: 30 white-coat hypertensives (age 16.3 ± 1.3 years, mean ± SD), 30 essential hypertensives (age 16.4 ± 1.3 years), and 46 healthy controls (age 16.2 ± 1.4 years). Ultrasound scans of the right brachial artery were performed using Prosound F75 Aloka system during protocol: baseline (1 min), forearm ischemia (5 min), and post-occlusion phase (3 min). FMD (%) was expressed as a change of the arterial diameter from baseline to maximum post-occlusion value and the values < 5% were considered as deficient FMD. We found significantly lower FMD in both essential and white-coat hypertension compared to control group (p < 0.05 for both) with no significant difference between the hypertensive groups. Deficient FMD was found in both hypertensive groups, but not in the control group. The occurence of deficient FMD was significantly higher in both essential and white-coat hypertensives compared to controls (p < 0.01 for both) with no significant difference between the hypertensive groups. Our findings of endothelial dysfunction indicated by impaired FMD in pediatric patients with white-coat hypertension could help to elucidate the mechanisms of the increased cardiovascular risk that could be similar as found in essential hypertension; therefore, white-coat hypertension should not be considered a benign phenomenon.

Improved assessment of arterial stiffness using corrected cardio-ankle vascular index (CAVI0) in overweight adolescents with white-coat and essential hypertension.

Arterial stiffness is a marker of vascular damage. Although adiposity increases cardiovascular risk, the relationship between paediatric overweight and arterial stiffness is unclear. The study aimed to evaluate the simultaneous effect of hypertension and overweight on arterial stiffness using cardio-ankle vascular index (CAVI) and related novel, theoretically blood pressure (BP)-independent, index CAVI0. CAVI and CAVI0 were measured in 140 adolescent boys (16.0 ± 1.9 years) divided into age-matched groups: normal-weight normotensives, overweight normotensives, overweight white-coat hypertensives, and overweight essential hypertensives. Overweight normotensives had significantly lower CAVI and CAVI0 compared to normal-weight normotensives (4.81 ± 0.64 vs. 5.33 ± 0.66, p < .01; 7.10 ± 0.99 vs. 7.81 ± 1.00, p < .01, respectively). CAVI and CAVI0 in overweight essential hypertensives showed no significant difference compared to normal-weight normotensives and were significantly higher compared to overweight normotensives (5.32 ± 0.77 vs. 4.81 ± 0.64, p < .01; 7.77 ± 1.19 vs. 7.10 ± 0.99, p < .01, respectively). CAVI, but not CAVI0, was associated positively with diastolic pressure (0.022 mmHg-1, p = .002) and negatively with pulse pressure (-0.022 mmHg-1, p = .001), and it was significantly higher in overweight white-coat hypertensives compared to overweight normotensives (5.20 ± 0.63 vs. 4.81 ± 0.64, p < .05). The lowering effect of overweight on arterial stiffness indexed by CAVI and CAVI0 in hypertensive adolescents seems to counterbalance the early arteriosclerotic effect of essential hypertension. The increase in CAVI, but not CAVI0, in overweight white-coat hypertensives could be attributable to residual BP dependence of CAVI, which is not present in CAVI0. Under certain conditions, CAVI0 may offer a clinically relevant improved assessment of arterial stiffness superior to CAVI.

Symbolic dynamics of heart rate variability - a promising tool to investigate cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD)?

We aimed to evaluate complex cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD) by using heart rate variability (HRV) nonlinear analysis - symbolic dynamics. We examined 29 boys with untreated ADHD and 25 healthy boys (age 8-13 years). ADHD symptoms were evaluated by ADHD-RS-IV scale. ECG was recorded in 3 positions: baseline supine position, orthostasis, and clinostasis. Symbolic dynamics indices were used for the assessment of complex cardiac sympathovagal regulation: normalised complexity index (NCI), normalised unpredictability index (NUPI), and pattern classification measures (0V%, 1V%, 2LV%, 2UV%). The results showed that HRV complexity was significantly reduced at rest (NUPI) and during standing position (NCI, NUPI) in ADHD group compared to controls. Cardiac-linked sympathetic index 0V% was significantly higher during all posture positions and cardiovagal index 2LV% was significantly lower to standing in boys suffering from ADHD. Importantly, ADHD symptom inattention positively correlated with 0V%, and negatively correlated with NCI, NUPI. Concluding, symbolic dynamics revealed impaired complex neurocardiac control characterised by potential cardiac beta-adrenergic overactivity and vagal deficiency at rest and to posture changes in boys suffering from ADHD that is correlated with inattention. We suggest that symbolic dynamics indices could represent promising cardiac biomarkers in ADHD.

Effect of Acute Ketamine Treatment on Sympathetic Regulation Indexed by Electrodermal Activity in Adolescent Major Depression.

Ketamine is a potential rapid-onset antidepressant characterized by sympathomimetic effects. However, the question of ketamine's use in treating adolescents' major depressive disorder (MDD) is still discussed. Thus, we aimed to study the acute effect of ketamine infusion treatment on sympathetic regulation using electrodermal activity (EDA) in addition to an assessment of depressive symptomatology in MDD adolescents. Twenty hospitalized adolescent girls with MDD (average age: 15.0 ± 1.46 yrs.) were examined before and two hours after a single intravenous infusion of ketamine. EDA was continuously recorded for 6 min, and depressive symptoms were assessed before and two hours after ketamine administration. The evaluated parameters included skin conductance level (SCL), nonspecific electrodermal responses (NS-SCRs), MADRS (questions no. 1-10, total score), and CDI (items A-E, total score). EDA parameters showed no significant changes after the ketamine treatment, and depressive symptoms were significantly reduced after the ketamine infusion. The analysis revealed a significant negative correlation between index SCL and CDI-A, CDI-E, and the total CDI score and between index NS-SCRs and MADRS no. 4 before the ketamine treatment. In conclusion, ketamine improved depressive symptomatology without a significant effect on EDA, indicating its potential safety and efficiency as an acute antidepressant intervention in adolescent MDD.

Vortioxetine's impact on the autonomic nervous system in depressed children and adolescents: analysis of the heart rate variability.

Relationship between depressive disorder and autonomic nervous system has been already discussed. Reduced emotional regulation is supposed to be associated with prefrontal hypofunction and subcortical hyperactivity. The aim of this study was to determine the effect of vortioxetine on heart rate variability (HRV), a parameter of cardiac autonomic regulation, in depressed hospitalized paediatric patients and assess the clinical effectiveness of the drug in this population. We performed repeated polysomnography analyses at admission and after a short treatment in hospital (15.2 days on average) and measured various HRV parameters (RRi, pNN50, RMSSD, LF-HRV, HF-HRV) during wakefulness, N3 and REM sleep stages. Out of 27 study subjects, 67% have improved depression symptoms as well as anxiety and subjective sleep quality after short vortioxetine treatment. We have found a significant decrease in parasympathetic parameters pNN50, RMSSD and HF-HRV during N3 sleep phase, though not exclusively among vortioxetine responders. The anticipated increase in cardiovagal regulation after vortioxetine treatment was not demonstrated in this pilot study, possibly due to the drug's multimodal mechanism and impact on the nucleus tractus solitarii, particularly its antagonism on 5HT-3 receptors. Application of selective drugs could further explain the effect of vortioxetine on HRV in depressed patients.

Cardiac Autonomic Balance Is Altered during the Acute Stress Response in Adolescent Major Depression-Effect of Sex.

Autonomic nervous system (ANS) abnormalities are associated with major depressive disorder (MDD) already at adolescent age. The majority of studies so far evaluated parasympathetic and sympathetic branches of ANS individually, although composite indices including cardiac autonomic balance (CAB) and cardiac autonomic regulation (CAR) seem to measure ANS functioning more comprehensively and thus could provide better psychopathologies' predictors. We aimed to study CAB and CAR derived from high-frequency bands of heart rate variability and left ventricular ejection time during complex stress response (rest-Go/NoGo task-recovery) in MDD adolescents with respect to sex. We examined 85 MDD adolescents (52 girls, age: 15.7 ± 0.14 yrs.) and 80 age- and sex-matched controls. The MDD group showed significantly reduced CAB compared to controls at rest, in response to the Go/NoGo task, and in the recovery phase. Moreover, while depressed boys showed significantly lower CAB at rest and in response to the Go/NoGo task compared to control boys, depressed girls showed no significant differences in evaluated parameters compared to control girls. This study for the first time evaluated CAB and CAR indices in drug-naïve first-episode diagnosed MDD adolescents during complex stress responses, indicating an altered cardiac autonomic pattern (i.e., reciprocal sympathetic dominance associated with parasympathetic underactivity), which was predominant for depressed boys.

Effects of Vortioxetine on Sleep Architecture of Adolescents with Major Depressive Disorder.

The relationship between depression and insomnia is bidirectional and both conditions need to be treated adequately, especially in a vulnerable neurodevelopmental stage of adolescence. This study aimed to evaluate the effects of antidepressant treatment using vortioxetine (VOR) on the sleep architecture of depressed adolescents by using video-polysomnography (v-PSG), which has not been researched before. The v-PSG was performed on 30 adolescent in-patients (mean age of 15.0 years ± 1.5 SD, 21 girls) treated with VOR (dosage of 10/15/20 mg/day) administered orally once a day, before and after VOR treatment. The evaluated parameters were conventional sleep parameters, sleep fragmentation parameters, and selected spectral power indices. Symptoms of depression and insomnia before and after the treatment period were evaluated using valid and reliable questionnaires (the Children´s Depression Inventory and the Athens Insomnia Scale). Depressed adolescents showed higher REM latency and decreased REM sleep percentage after treatment than before the treatment period (p = 0.005, p = 0.009, respectively). Our study revealed REM suppression (increased REM latency and reduced REM sleep percentage), indicating altered sleep architecture as a potential result of VOR treatment, which seems to be dose-dependent.

Major depressive disorder at adolescent age is associated with impaired cardiovascular autonomic regulation and vasculature functioning.

Cardiovascular adverse complications represent a risk factor for increased cardiovascular morbidity and mortality in patients with major depressive disorder (MDD). However, there is little knowledge of adolescent MDD. We aimed to study complex cardiovascular autonomic regulation and early atherosclerotic damage with a focus on an analysis of heart rate variability (HRV), blood pressure variability (BPV), systolic time intervals, and measures of early atherosclerotic changes in adolescent MDD. Ninety depressive adolescents (34 boys, age 15.8 ± 1.3 yrs.) and 90 age-/gender-matched controls were examined. Evaluated parameters: HRV - time and spectral parameters, BPV - mean, systolic, and diastolic blood pressure, spectral systolic parameters; haemodynamic indices - stroke volume, cardiac output, total peripheral resistance, systolic time intervals - left ventricular ejection time, pre-ejection period; atherosclerotic indices - ankle-brachial index (ABI), pulse wave velocity, brachial-ankle pulse wave velocity, cardio-ankle vascular index; growth factors - epidermal growth factor (EGF), vascular endothelial growth factor associated with monocyte chemoattractant protein-1. Our results showed that the MDD group had significantly reduced HRV and higher BPV measures, shortened systolic time intervals, lower ABI, and higher EGF compared to controls. Concluding, our study revealed that adolescent MDD is associated with cardiovascular dysregulation and early vasculature dysfunction as preclinical markers of higher risk for cardiovascular morbidity, thus adolescence seems to represent an important age period for early diagnosis and prevention of later MDD-linked cardiovascular diseases manifesting in adulthood.

Evaluation of Inflammatory Response System (IRS) and Compensatory Immune Response System (CIRS) in Adolescent Major Depression.

Purpose: Nowadays, the role of two tightly interconnected systems, the inflammatory response system (IRS) and the compensatory immune response system (CIRS) in depression, is increasingly discussed. Various studies indicate pro-inflammatory activity in adolescent depression; however, there is an almost complete lack of findings about IRS and CIRS balance. Thus, we aimed to assess different IRS and CIRS indices, profiles, and IRS/CIRS ratios in drug-naïve MDD patients at adolescent age, with respect to sex. Patients and Methods: One hundred MDD adolescents (40 boys, average age: 15.4±1.2 yrs.) and 60 controls (28 boys, average age: 15.3±1.5 yrs.) were examined. Evaluated parameters were 1. plasma levels of interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, interferon gamma, tumor necrosis factor alpha (TNF-α), soluble receptor of IL-6 (sIL-6R), soluble receptors of TNF-α (sTNF-R1, sTNF-R2); 2. profiles: IL-6 trans-signaling, M1 macrophage signaling, helper T lymphocytes (Th) 1 profile, regulatory T lymphocytes (Treg)+Th2, allIRS, and allCIRS; 3. IRS vs CIRS activity ratios: TNF-α/TNF-R1, TNF-α/TNF-R2, TNF-α/sTNF-Rs (ie sTNF-R1+sTNF-R2), Th1/Th2, Th1/Treg, Th1/Th2+Treg, M1/Th2, M1/Treg, M1/Treg+Th2, allIRS/allCIRS. Results: MDD patients showed increased IL-4, IL-10, TNF-α, sIL-6R, Treg+Th2, allIRS, allCIRS, and TNF-α/sTNF-Rs, and decreased Th1/Th2+Treg. MDD females showed increased IL-10 and TNF-α compared to control females. MDD males showed increased IL-4, IL-10, sIL-6R, Treg+Th2, and TNF-α/TNF-R1 compared to control males. Increased sTNF-R1 was found in MDD males compared to MDD females. Positive correlations were found between CDI score and sIL-6R and IL-10 in the total group and between CDI score and IL-10 in adolescent males. Conclusion: Our study for the first time extensively evaluated IRS and CIRS interactions revealing enhanced pro-inflammatory TNF-α signaling and IL-6 trans-signaling in association with increased IL-10- and IL-4-mediated anti-inflammatory activity in first-episode depression at the adolescent age. Moreover, results reflect the sex-specific simultaneous activation of IRS and CIRS pathways in adolescent depression.

The Plasma Levels of 3-Hydroxybutyrate, Dityrosine, and Other Markers of Oxidative Stress and Energy Metabolism in Major Depressive Disorder.

Major depressive disorder (MDD) is a serious mental disease with a pathophysiology that is not yet fully clarified. An increasing number of studies show an association of MDD with energy metabolism alteration and the presence of oxidative stress. We aimed to evaluate plasma levels of 3-hydroxybutyrate (3HB), NADH, myeloperoxidase, and dityrosine (di-Tyr) in adolescent and adult patients with MDD, compare them with healthy age-matched controls, and assess the effect of antidepressant treatment during hospitalisation on these levels. In our study, plasmatic levels of 3HB were elevated in both adolescents (by 55%; p = 0.0004) and adults (by 88%; p < 0.0001) with MDD compared to controls. Levels of dityrosine were increased in MDD adults (by 19%; p = 0.0092) but not adolescents. We have not found any significant effect of antidepressants on the selected parameters during the short observation period. Our study supports the findings suggesting altered energy metabolism in MDD and demonstrates its presence independently of the age of the patients.

Complex cardiac vagal regulation to mental and physiological stress in adolescent major depression.

BACKGROUND: Cardiovagal control is known to be reduced in major depressive disorder (MDD), however, the neurocardiac reflex control to distinct types of stressors is still unclear. We aimed to study parasympathetically mediated cardiac reflex functioning in response to mental and physiological stressors using heart rate variability (HRV) linear and nonlinear analysis in adolescent MDD. METHODS: We examined 60 adolescents (40 girls) with MDD (age 14.9 ±â€¯0.3 years) and 60 age and gender-matched controls. ECG was continuously recorded during stress protocol: baseline, Go/NoGo test, recovery, supine position, and orthostasis. Evaluated HRV linear and nonlinear indices: RR interval, pNN50, rMSSD, HF-HRV, Poincaré plot (SD1), symbolic dynamics 2UV%. Cardiovagal reactivity expressed as percentual change (%) was calculated in response to both stressors. RESULTS: In each phase of stress protocol, the MDD group had significantly reduced HRV parameters compared to controls, except for symbolic dynamics index 2UV% in supine position. The reactivity of HRV indices was significantly greater in response to orthostasis in MDD compared to controls. No significant differences were found in response to Go/NoGo test. LIMITATIONS: The smoking status and the menstrual cycle phase potentially affecting the HRV parameters were not monitored. Future research is needed to expand a sample size with respect to sex and to study neurocardiac response to other different stressors in MDD. CONCLUSIONS: This study revealed reduced resting cardiovagal regulation and greater vagal withdrawal indicating abnormal neurocardiac reflex functioning to physiological stressor (orthostasis) in adolescent MDD patients. Nonlinear HRV analysis was sensitive to detect cardiac-linked regulatory differences in adolescent depression.