Alternations in the Cardiovascular Autonomic Regulation and Growth Factors in Autism.

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 (p<0.05). 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.

The impact of external stress factors on hippocampus volume during antidepressant treatment

Background and objectives: Magnetic resonance imaging (MRI) studies suggest that depression is associated with volumetric hippocampal changes. Investigations of these structures during antidepressant therapy is therefore important, however, volumetric studies are rare in this case. We aimed to study the effect of AD treatment on volumetric changes in hippocampus depending on stress factors in depressive patients.MethodsThirty patients with major depressive disorder (MDD) underwent MRI of the brain on the day of admission and at the time of stabilization of acute depressive symptomatology by venlafaxine. The presence of long-lasting stress factors in these patients was investigated by the social readjustment rating scale questionnaire.ResultsNo significant differences were found in hippocampi volumes before and after venlafaxine treatment. However, regression analysis revealed significant positive relation between stress factors and volumetric hippocampus change during AD treatment.ConclusionIt seems that antidepressant treatment by venlafaxine could be more suitable in the MDD patients with presence of stress-factors. (AU)

Central autonomic regulation assessed by pupillary light reflex is impaired in children with attention deficit hyperactivity disorder.

It is assumed that the Attention Deficit Hyperactivity Disorder is associated with the central autonomic dysregulation, however, the studies are rare. Analysis of pupillary light reflex represents a non-invasive tool to provide information related to the central autonomic regulation; thus, we aimed to evaluate potential disturbances in the central autonomic integrity using pupillary light reflex examination in Attention Deficit Hyperactivity Disorder. We have examined 20 children with Attention Deficit Hyperactivity Disorder (10 boys, 13.0+/-2.3 years) and 20 age/gender-matched healthy subjects. Pupillary light reflex was examined at rest for both eyes using Pupillometer PLR-2000 (NeurOptics, USA). Evaluated parameters were: diameter of the pupil before the application of light stimulus and after illumination at the peak of the constriction, the percentual change of the pupil diameter during constriction, average constriction velocity, maximum constriction velocity and average dilation velocity. We found significantly lower percentual change of the pupil diameter during constriction for both eyes in Attention Deficit Hyperactivity Disorder group compared to controls (right eye: -25.81+/-1.23 % vs. -30.32+/-1.31 %, p<0.05, left eye: -25.44+/-1.65 % vs. -30.35+/-0.98 %, p<0.05). The average constriction velocity and maximum constriction velocity were significantly shortened in left eye in Attention Deficit Hyperactivity Disorder group compared to controls (p<0.05). Our findings revealed altered pupillary light reflex indicating abnormal centrally-mediated autonomic regulation characterized by parasympathetic underactivity associated with relative sympathetic predominance in children suffering from Attention Deficit Hyperactivity Disorder.

Potential major depressive disorder biomarkers in pediatric population - a pilot study.

Mental disorders affect 10-20 % of the young population in the world. Major depressive disorder (MDD) is a common mental disease with a multifactorial and not clearly explained pathophysiology. Many cases remain undetected and untreated, which influences patients' physical and mental health and their quality of life also in adulthood. The aim of our pilot study was to assess the prediction value of selected potential biomarkers, including blood cell counts, blood cell ratios, and parameters like peroxiredoxin 1 (PRDX1), tenascin C (TNC) and type IV collagen (COL4) between depressive pediatric patients and healthy peers and to evaluate a short effect of antidepressant treatment. In this study, 27 young depressive patients and 26 non-depressed age-matched controls were included. Blood analyses and immunological assays using commercial kits were performed. Platelet count was the only blood parameter for which the case/control status was statistically significant (p=0.01) in a regression model controlling for the age and gender differences. The results from ELISA analyses showed that the case/control status is a significant predictor of the parameters PRDX1 (p=0.05) and COL4 (p=0.009) in respective regression model considering the age and gender differences between MDD patients and controls. A major finding of this study is that values of platelet count, monocyte to lymphocyte ratio, white blood cell, and monocyte counts were assessed by the Random Forest machine learning algorithm as relevant predictors for discrimination between MDD patients and healthy controls with a power of prediction AUC=0.749.

Autism spectrum disorder is associated with autonomic underarousal.

Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder, associated with autonomic dysregulation. However, the pathomechanism leading to autonomic abnormalities is still unclear. The aim of this study was to assess autonomic nervous system (ANS) activity during baseline in homogenous group of autistic children using electrodermal activity (EDA), as an index of sympathetic activity and short-term heart rate variability (HRV) reflecting predominantly cardiac vagal control. Fifteen ASD boys and 15 healthy age-matched boys at the age of 7-15 years were examined. The continuous EDA and ECG were recorded during resting phase in a supine position. Evaluated parameters: EDA amplitude (microS), RR interval, spectral power, peak frequency and power spectral density in low (LF-HRV: 0.04-0.15 Hz) and high-frequency (HF-HRV: 0.15-0.4 Hz) bands of HRV spectral analysis. In ASD group we found significantly shortened RR intervals (729+/-20 ms vs. 843+/-30 ms, p=0.005), lower mean EDA (0.66+/-0.13 microS vs. 1.66+/-0.42 microS, p=0.033), reduced spectral activity and power spectral density in HF-HRV compared to controls (2.93+/-0.12 ms(2) vs. 3.38+/-0.10 ms(2), p=0.01; 4.12+/-0.10 ms(2)/Hz vs. 4.56+/-0.11 ms(2)/Hz, p=0.008, respectively). We suggest that impairment in resting autonomic regulation associated with ASD could represent an important pathomechanism leading to potential cardiovascular complications in ASD.

Electrodermal Activity in Adolescent Depression.

Major depressive disorder (MDD) is characterized by dysphoric mood, which may be accompanied by suicidal ideation. It is supposed that MDD is associated with dysfunction of the autonomic nervous system, but studies in pediatric patients are rare. Therefore, we aimed to study the relationship between MDD and autonomic regulation in adolescence using the electrodermal activity as an index of sympathetic cholinergic control. We examined 25 adolescents suffering from MDD without comorbidities and prior to pharmacotherapy (13 girls, mean age 14.6 ± 0.4 year) and 25 age/gender-matched healthy control subjects. The electrodermal activity was continuously recorded during 5 min of supine rest. The value of this activity in µS was averaged for each minute of the recording. We found that in depressed patients, electrodermal activity was significantly lower each minute of the recording compared to that in the control group. The study demonstrates electrodermal hypoactivity in adolescent patients with MDD, which points to dysfunctional regulation of the sympathetic part of the autonomic nervous system. This finding could represent a potential pathomechanism leading to higher risk of negative health outcomes in pediatric depressed patients. Further research is needed to elucidate the incompletely understood interaction between MDD and autonomic regulatory outputs at young age.

Inflammatory Activity in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder in early childhood characterized by impairment in communication and behavior. Recent research is focused on the immune dysregulation as a potential pathomechanism leading to ASD. Thus, we addressed the hypothesis that inflammatory activity might be enhanced in children suffering from ASD. We examined 15 children with ASD (13 boys/2 girls, mean age of 9.3 ± 0.7 years) and 20 age/gender-matched healthy subjects as a control group. All children were medication free and in good health. Hematological parameters in venous blood and plasma levels of pro-inflammatory cytokines - tumor necrosis factor alpha (TNF-α), interleukin 1ß (IL-1ß), and interleukin 8 (IL-8) - were assessed in each subject using human ultra-sensitive ELISA kits. In addition, TBARS as a marker of oxidative stress was evaluated. We found that the level of IL-8 was significantly increased in the ASD children, whereas the other markers remained unappreciably changed compared to controls (p = 0.003). In conclusion, the study demonstrates a discrete immune dysfunction in ASD of pro-inflammatory character.