If the eyes are windows into the soul, then the pupils represent at least the gateway to the brain and can provide a unique insight into the human mind from several aspects. The changes in the pupil size primarily mediated by different lighting conditions are controlled by the autonomic nervous system regulated predominantly at the subcortical level. Specifically, parasympathetically-linked pupillary constriction is under the Edinger-Westphal nucleus control and sympathetically-mediated pupillary dilation is regulated from the posterior hypothalamic nuclei. However, the changes in the pupil size can be observed at resting state even under constant lighting, these pupillary changes are mediated by global arousal level as well as by various cognitive factors. In this context, autonomic pathways modulating changes in the pupil size in response to the different light levels can be influenced by multiple central descending inputs driving pupillary changes under steady lighting conditions. Moreover, as the pupillary response is involved in emotional (task-evoked pupillary dilation as an index of emotional arousal) and cognitive (task-evoked pupillary dilation as an index of cognitive workload) stimulation, it can be used to detect the impact of mutual subcortical and cortical structures (i.e. overlapping brain structures included in autonomic, emotional and cognitive regulation) on the pupillary innervation system. Thus, complex understanding of the baseline pupil size´ and pupillary dynamics´ mechanisms may provide an important insight into the central nervous system functioning pointing to the pupillometry as a promising tool in the clinical application.
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-1β, 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.
Autism spectrum disorder (ASD) represents a serious neurodevelopmental disorder associated with autonomic nervous system dysregulation. The aim was to study complex cardiovascular autonomic regulation using heart rate variability (HRV) and systolic blood pressure variability (SBPV) linear/non-linear analysis at rest and during orthostasis, and to assess plasma levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) in autistic children. Twenty-five ASD boys and 25 age and gender-matched children at the age 7 15 years were examined. After venous blood taking, continuous ECG and blood pressure biosignals were recorded at rest and during orthostasis. Evaluated parameters: RR intervals, high- and low-frequency band of HRV spectral analysis (HF-HRV, LF-HRV), symbolic dynamics parameters 0V %, 1V %, 2LV %, 2UV %, low- and high-frequency band of SBPV (LF-SBPV, HF-SBPV), systolic, diastolic, mean blood pressure, EGF, VEGF plasma levels. RR intervals were significantly shortened and the HF-HRV, LF-SBPV, HF-SBPV parameters were significantly lower at rest, the HF-HRV and LF-SBPV remained lower during orthostasis in autistic children compared to controls (p0.05). EGF plasma levels were significantly lower in ASD compared to controls (p=0.046). No significant differences were found in remaining parameters. Our study revealed tachycardia, cardiovagal underactivity, and blunted sympathetic vasomotor regulation at rest and during orthostasis in autistic children. Additionally, complex heart rate dynamics are similar in autistic children than controls. Furthermore, EGF was reduced in autistic children without significant correlations with any autonomic parameters. We suggest that the abnormal complex cardiovascular reflex control could contribute to understanding the pathway linking autonomic features and autism.
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.
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