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.

Pycnogenol supplementation as an adjunct treatment for antidepressant-induced sexual dysfunction.

INTRODUCTION: Major depressive disorder is a serious mental disorder in which treatment with antidepressant medication is associated with incidence of adverse events, such as constipation, diarrhea, dry mouth, headache, insomnia, and sexual dysfunction (SDys). Escitalopram (ESC), an effective and safe selective serotonin reuptake inhibitor with good tolerability, was used in this study. In this study, we investigated the prospective effect of Pycnogenol (PYC), an antioxidant, anti-inflammatory, and vasodilator agent, on ESC-induced SDys. METHODS: This was a randomized, parallel, open-label study. Seventy-two outpatients of both genders with depression were randomized into two groups as follows: 37 patients from the ESC + PYC group took 50 mg of PYC per day for 4 months in ESC co-treatment, and 35 subjects from the ESC group took ESC only. Five patients dropped out and were excluded from the analysis. The participants were examined every month (visits 1-4). RESULTS: ESC use led to improvement of depressive symptoms and severity scored by standardized psychiatric tests. PYC co-treatment resulted in attenuation of SDys beginning at 1 month of treatment and continuing for two consecutive months. Furthermore, an increase in heart rate in the PYC group was registered. CONCLUSIONS: We propose that PYC-mediated SDys attenuation is based on its ability to improve endothelial functions by its antioxidant, anti-inflammatory, vasodilatory, and anticoagulant action. We assume that the action of PYC on heart rate is in accordance with the aforementioned vasodilatory action of PYC and consequent baroreflex-mediated heart rate response. PYC co-treatment reduced ESC-induced SDys and elevated heart rate.

Oculometric behavior assessed by pupil response is altered in adolescent depression.

Oculometric behaviour assessed by pupil response provides important information about central autonomic activity and emotional regulation. However, studies regarding pupil response to emotional stimuli in adolescent depression are rare. We aimed to study emotional-linked pupil response in adolescent depression. Twenty depressive adolescents (average age: 15.4+/-1.2 years) and 20 age/gender-matched healthy subjects were examined. Average pupil diameter assessed by eye-tracking and pupillary light reflex were evaluated during protocol - baseline, free-view task, recovery phase. Regarding right eye, significantly greater initial pupil diameter and pupil dilation to positive pictures free-viewing (p=0.013, p=0.031, respectively), significantly slower average and maximum constriction velocity in baseline and positive pictures free-viewing (p=0.036, p=0.050, p=0.021, p=0.015, respectively), significantly slower maximum constriction velocity in recovery phase (p=0.045), and significantly faster average dilation velocity in negative pictures free-viewing (p=0.042) were observed in depressive group. Regarding left eye, significantly lower constriction percentual change in negative pictures free-viewing (p=0.044) and significantly greater baseline pupil diameter and pupil diameter at the peak of constriction in positive vs. negative pictures free-viewing (p=0.002, p=0.015, respectively) were observed in depressive group. Our study revealed discrete central autonomic dysregulation - parasympathetic hypoactivity associated with relative sympathetic dominance influenced by impairments in emotional processing already in adolescent depression.

Pupillary light reflex is altered in adolescent depression.

Major depressive disorder is associated with abnormal autonomic regulation which could be noninvasively studied using pupillometry. However, the studies in adolescent patients are rare. Therefore, we aimed to study the pupillary light reflex (PLR), which could provide novel important information about dynamic balance between sympathetic and parasympathetic nervous system in adolescent patients suffering from major depression. We have examined 25 depressive adolescent girls (age 15.2+/-0.3 year) prior to pharmacotherapy and 25 age/gender-matched healthy subjects. PLR parameters were measured separately for both eyes after 5 min of rest using Pupillometer PLR-2000 (NeurOptics, USA). The constriction percentual change for the left eye was significantly lower in depressive group compared to control group (-24.12+/-0.87 % vs. -28.04+/-0.96 %, p<0.01). Furthermore, average constriction velocity and maximum constriction velocity for the left eye were significantly lower in depressive group compared to control group (p<0.05, p<0.01, respectively). In contrast, no significant between-groups differences were found for the right eye. Concluding, this study revealed altered PLR for left eye indicating a deficient parasympathetic activity already in adolescent major depression. Additionally, the differences between left and right eye could be related to functional lateralization of autonomic control in the central nervous system.

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.

Attention deficit/hyperactivity disorder (ADHD) is associated with altered heart rate asymmetry.

Attention deficit/hyperactivity disorder (ADHD) is associated with complex neurocardiac integrity. We aimed to study heart rate time asymmetry as a nonlinear qualitative feature of heart rate variability indicating complexity of cardiac autonomic control at rest and in response to physiological stress (orthostasis) in children suffering from ADHD. Twenty boys with ADHD and 20 healthy age-matched boys at the age of 8 to 12 years were examined. The continuous ECG was recorded in a supine position and during postural change from lying to standing (orthostasis). Time irreversibility indices - Porta's (P%), Guzik's (G%) and Ehlers' (E) - were evaluated. Our analysis showed significantly reduced heart rate asymmetry indices at rest (P%: 49.8 % vs. 52.2 %; G%: 50.2 % vs. 53.2 %; p<0.02), and in response to orthostatic load (P%: 52.4 % vs. 54.5 %, G%: 52.3 % vs. 54.5 %; p<0.05) associated with tachycardia in ADHD children compared to controls. Concluding, our study firstly revealed the altered heart rate asymmetry pattern in children suffering from ADHD at rest as well as in response to posture change from lying to standing (orthostasis). These findings might reflect an abnormal complex cardiac regulatory system as a potential mechanism leading to later cardiac adverse outcomes in ADHD.

Correlations of ADHD symptoms with neurometabolites measured by 1H magnetic resonance spectroscopy.

OBJECTIVES: Despite the number of studies on neurometabolite changes in ADHD (Attention deficit/hyperactivity disorder), there is lack of evidence on neurometabolite associations with ADHD symptoms. BACKGROUND: We aimed to find the correlations of neurometabolites with ADHD symptoms. METHODS: Twenty ADHD children were examined by means of 1H-MRS. The spectra were taken from dorsolateral prefrontal cortex (DLPFC) and white matter behind DLPFC, bilaterally. Neurometabolites were correlated with ADHD-RS-IV (ADHD-Rating Scales IV), CPRS (Conners Parent rating Scale) and DPREMB (Daily Parent Rating of Evening and Morning Behavior) scores. RESULTS: NAA/Cr (N-acetylaspartate/creatine) in the right DLPFC positively correlated with CPRS subscale IV learning problems and negatively correlated in the left white matter with DPREMB morning behavior subscale and ADHD-RS-IV score. Glx/Cr (glutamate + glutamine/creatine) positively correlated in the right white matter with ADHD-RS-IV and negatively correlated in the left white matter with DPREMB morning behavior subscale score. Cho/Cr (choline/creatine) in the left white matter negatively correlated with DPREMB morning behavior subscale and ADHD-RS-IV score. CONCLUSION: ADHD symptoms could result from different activities of the left- and right-hemisphere prefrontal circuits. In consequence to impulses to novel task searching the increased right prefrontal circuit activity could be mediated by different motivational control (Fig. 9, Ref. 73).

Metabolic risk in selected second-generation antipsychotics.

BACKGROUND: Many studies have reported higher incidence of metabolic abnormalities in patients receiving antipsychotic medications than in general population. OBJECTIVES: The objective of our study was to determine the prevalence of metabolic syndrome in a group of patients receiving long-lasting antipsychotic treatment and also whether the cardiovascular risk among different second-generation antipsychotics varies. METHODS: Our study group consisted of 71 patients who were on antipsychotic monotherapy for at least 12 months. In each patient, fasting plasma glucose, HDL cholesterol, triglycerides, liver enzymes, bilirubin and plasma immunoreactive insulin levels were examined. We measured body weight, height, body mass index, waist circumference and body fat percentage together with blood pressure and heart rate. We assessed metabolic syndrome prevalence in the study group and correlations among its components as well as between them and other variables. The data were processed by statistics programme STATISTICA 8.0. For detection of correlations Spearman's rank correlation test was used. RESULTS: The prevalence of metabolic syndrome in our sample reached 41%. The highest prevalence rate of 50% was detected in the olanzapine subgroup. Identical prevalence of 40% was observed in quetiapine and risperidone subgroups. The lowest prevalence of 25% and 31% was observed in sertindol and amisulpirid subgroup, respectively. The prevalence rate of metabolic syndrome in men was 51% compared to 34% in women. CONCLUSION: According to metabolic syndrome prevalence rates olanzapine appears to be associated with the highest cardiovascular risk, amisulpirid and sertindol appear to be much safer (Tab. 2, Ref. 13).

Respiratory sinus arrhythmia is reduced in adolescent major depressive disorder.

OBJECTIVE: Although the emotion regulatory difficulties in patients with major depressive disorder (MDD) are predicted to associate with impaired cardiovascular autonomic regulation, the changes of cardiac vagal regulation MDD are incompletely understood. The aim of the study was to evaluate the respiratory sinus arrhythmia (as an index of cardiac vagal regulation) using the spectral analysis in high frequency band of the heart rate variability and the indices of deep breathing test in adolescent patients with major depressive disorder. MATERIAL AND METHOD: Twenty-eight adolescent girls were examined - 14 patients with major depressive disorder without pharmacological treatment (average age: 16.4 +/- 0.2 yr) and 14 healthy probands (control group) matched for age and gender. The respiratory sinus arrhythmia was evaluated using the spectral analysis in high frequency band of the heart rate variability (HF-HRV) and the parameters of deep breathing test (I-E, I/E). In addition, mean R-R interval was calculated. RESULTS: The adolescent patients with MDD has significantly reduced spectral activity in the HF-HRV and lower I/E, I-E parameters compared to marched health subjects (P<0.05). CONCLUSIONS: We conclude that the adolescents girls with MDD have reduced respiratory sinus arrhythmia indicating cardiac vagal dysregulation. Since impaired cardiac vagal regulation is associated with increased risk of cardiovascular morbidity, this finding underscores the importance of impaired autonomic neuro-cardiac integrity already in adolescents with major depressive disorder without pharmacological treatment.