Novel approach to evaluate central autonomic regulation in attention deficit/hyperactivity disorder (ADHD).

Attention deficit/hyperactivity disorder (ADHD) is one of the most commonly diagnosed developmental disorders in childhood characterized by hyperactivity, impulsivity and inattention. ADHD manifests in the child's development by deficits in cognitive, executive and perceptor-motor functions, emotional regulation and social adaptation. Although the exact cause has not yet been known, the crucial role in the development of this disease plays the interaction of genetic, neurobiological and epigenetic factors. According to current knowledge, ADHD is defined as a biological dysfunction of central nervous system with genetically or organically defined deficits in noradrenergic and dopaminergic neurotransmission associated with structural abnormalities, especially in prefronto-striatal regions. In this context, a significant part of the difficulties could be due to a faulty control of fronto-striato-thalamo-cortical circuits important for attention, arousal and executive functions. Moreover, ADHD is associated with abnormal autonomic regulation. Specifically, reduced cardiac-linked parasympathetic activity associated with relative sympathetic dominance indexed by low heart rate variability can represent a noninvasive marker for prefrontal hypoactivity. However, the mechanisms underlying altered autonomic regulation in ADHD are still unknown. In this aspect, the evaluation of central autonomic regulation by noninvasive methods, namely pupillometry and eye-tracking, may provide novel information for better understanding of the neurobiological pathomechanisms leading to ADHD.

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.

Cardiac Vagal Control and Depressive Symptoms in Response to Negative Emotional Stress.

We aimed to study complex cardiovagal control using heart rate variability (HRV), linear and nonlinear analyses at rest and during negative emotional stress in healthy students with varying depressive symptoms. ECG recording in 20 students was performed at baseline, negative emotional stress, and recovery period. The HRV parameters evaluated were the following: RR interval, spectral power in high-frequency band (HF-HRV), and symbolic dynamics index 2LV%. The subjects were divided into two groups based on the score of the Beck Depression Inventory (BDI) - normal mood (BDI: 0.6 ± 0.2) and mild mood disturbance (BDI: 14.3 ± 1.4). We found significantly lower logHF-HRV during emotional stress in mild mood disturbance compared with normal mood (p = 0.047). No significant differences were found in the remaining parameters. We conclude that negative emotional stress attenuated the cardiovagal control during mood disturbance, which points to discrete abnormalities in the neurocardiac reflex system associated with depressive symptoms. Hampered cardiovagal control could represent a potential pathomechanism leading to depression-linked cardiovascular complications.

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.

Cardiovascular sympathetic arousal in response to different mental stressors.

The altered regulation of autonomic response to mental stress can result in increased cardiovascular risk. The laboratory tests used to simulate the autonomic responses to real-life stressors do not necessarily induce generalized sympathetic activation; therefore, the assessment of regulatory outputs to different effector organs could be important. We aimed to study the cardiovascular sympathetic arousal in response to different mental stressors (Stroop test, mental arithmetic test) in 20 healthy students. The conceivable sympathetic vascular index--spectral power of low frequency band of systolic arterial pressure variability (LF-SAP) and novel potential cardio-sympathetic index--symbolic dynamics heart rate variability index 0V% were evaluated. The heart and vessels responded differently to mental stress--while Stroop test induced increase of both 0V% and LF-SAP indices suggesting complex sympathetic arousal, mental arithmetic test evoked only 0V% increase compared to baseline (p<0.01, p<0.001, p<0.01, respectively). Significantly greater reactivity of LF-SAP, 0V%, heart rate (HR) and mean arterial pressure (MAP) were found in response to Stroop test compared to mental arithmetic test potentially indicating the effect of different central processing (0V%, LF-SAP: p<0.001; HR, MAP: p<0.01). The different effectors' sympathetic responses to cognitive stressors could provide novel important information regarding potential pathomechanisms of stress-related diseases.

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.