Igor Ondrejka

Cardiac autonomic regulation is impaired in girls with major depression.

UNLABELLED We aimed to study short-term heart rate variability (HRV) as an index of cardiac autonomic control in never-treated major depressive disorder (MDD) adolescent patients using linear and nonlinear analysis. METHODS We have examined 20 MDD girls and 20 healthy age-matched girls at the age of 15 to 18yr. The ECG was recorded in three positions: the 1st supine rest, orthostasis, the 2nd supine position. HRV magnitude was quantified by time and frequency-domain analysis (mean RR interval, SDRR, RMSSD, spectral powers in low [LF] and high frequency [HF] bands). In addition to linear measures, HRV complexity was assessed by nonlinear (symbolic dynamics) indices: normalized complexity index (NCI), normalized unpredictability index (NUPI), and pattern classification measures (0V%, 1V%, 2LV%, 2UV%). RESULTS HRV magnitude (RMSSD, SDRR, LF and HF powers) was significantly decreased in MDD group in a supine rest and after posture change. HRV complexity was significantly reduced (lower NCI) in the standing position. Pattern classification analysis revealed significantly higher 0V% and lower 2LV% in MDD group in supine position and orthostasis. CONCLUSION The HRV linear and nonlinear analysis revealed decreased magnitude and complexity of heart rate time series indicating altered neurocardiac regulation in girls with major depression without pharmacotherapy.

Respiratory sinus arrhythmia is reduced in adolescent major depressive disorder

ObjectiveAlthough 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 in 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.Materials and methodsTwenty-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.ResultsThe adolescent patients with MDD had significantly reduced spectral activity in the HF-HRV and lower I/E, I-E parameters compared to matched healthy subjects (P < 0.05).ConclusionsWe conclude that the adolescent 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 neurocardiac integrity already in adolescents with major depressive disorder without pharmacological treatment.

Hippocampal neurometabolite changes in depression treatment: A 1H magnetic resonance spectroscopy study

Previous studies using magnetic resonance spectroscopy have related abnormalities in hippocampal metabolism to depression. Current evidence is consistent with the conclusion that the hippocampal formation plays an important role in the presentation of depressive symptoms. Eighteen adult patients with major depressive disorder, aged 20 to 60 years, underwent magnetic resonance spectroscopy of the hippocampus during a period of depressive symptomatology and after 7-11 weeks of antidepressant medication with at least 50% reduction in the Montgomery-Åsberg Depression Rating Scale ()MADRS score. During therapy, we found a significantly decreased Lac/Cr ratio in the left hippocampus. The Ins/Cr ratio showed a significant negative correlation with the severity of depression as assessed by the MADRS at baseline. Moreover, we found a negative association of NAA/Cho with age and a positive association of Cho/Cr with age, both on the left and right sides at baseline. In light of our findings and previous studies results we hypothesize that mitochondrial dysfunction leading to predominantly anaerobic glycolysis in connection with the intracellular signaling pathways disturbances and decreased astrocytic function/number might subsequently lead to decreased brain neuroplasticity in depression. These mechanisms could be positively influenced by antidepressant treatment with selective serotonin or norepineprine reuptake inhibitors, with potential effects on untimely neuronal aging in depression.

A 12-Month Prospective, Observational Study of Treatment Regimen and Quality of Life Associated With ADHD in Central and Eastern Europe and Eastern Asia

Objectives: This prospective, observational, non-randomized study aimed to describe the relationship between treatment regimen prescribed and the quality of life (QoL) of ADHD patients in countries of Central and Eastern Europe (CEE) and Eastern Asia over 12 months. Methods: 977 Male and female patients aged 6-17 years seeking treatment for symptoms of ADHD were assessed using the Child and Adolescent Symptom Inventory-4 Parent Checklists, and the Clinical Global Impressions-ADHD-Severity scale. QoL was assessed using the Child Health and Illness Profile-Child Edition parent report form. Patients were grouped according to whether they were prescribed psycho- and/or pharmacotherapy (treatment) or not (no/‘other’ treatment). Results: No statistically significant differences were observed between cohorts (treatment vs. no/‘other’ treatment) in terms of change in QoL, although there was improvement over 12 months, with a greater improvement experienced by patients in the treatment cohort in both study regions (CEE and Eastern Asia). Psychoeducation/counselling and methylphenidate were the predominant ADHD treatments prescribed. Conclusions: Although both treatment and no/‘other’ treatment cohorts showed improvements in mean QoL over 12 months, the difference was small and not statistically significant. A major limitation was the higher than anticipated number of patients switching treatments, predominantly from the no/‘other’ treatment cohort.

Analysis of genetic polymorphisms of brain-derived neurotrophic factor and methylenetetrahydrofolate reductase in depressed patients in a Slovak (Caucasian) population.

Major depressive disorder (MDD) is a complex neuropsychiatric disorder where both gene-gene and gene-environment interactions play an important role, but the clues are still not fully understood. One carbon metabolism in the CNS plays a critical role in the synthesis and release of neurotransmitters which are relevant to depressive disorder. We studied genetic polymorphisms of the brain derived neurotrophic factor (BDNF) and the methylenetetrahydrofolate reductase (MTHFR) in association with major depressive disorder. We genotyped the BDNF G196A, the MTHFR C677T, and A1298C polymorphisms in 134 patients diagnosed with major depression and 143 control subjects in Slovak (Caucasian) cohort of patients and probands. We found no significant association of either the BDNF G196A or MTHFR C677T polymorphisms with major depressive disorder neither in female nor male group of patients. However, the MTHFR A1298C genotype distribution was 36.6% (for AA genotype), 48.5% (AC) and 14.9% (CC) for the depressed patients, and 48.9% (AA), 42.7% (AC) and 8.4% (CC), respectively, for the control subjects. Patients with MDD had a higher prevalence of the CC genotype (OR = 2.38; 95% CI = 1.07-5.32; p = 0.032) and the AC + CC genotype (OR = 1.67; 95% CI = 1.03-2.69; p = 0.037) in comparison with the control subjects. This study shows that CC genotype of the MTHFR A1298C is associated with higher risk of MDD in Slovak population.

Heart Rate Variability: An Index of the Brain-Heart Interaction

The autonomic nervous system plays an important role in a wide range of visceral-somatic and mental diseases. Cardiac parameters, particularly heart rate as a physiological measure, are extremely sensitive to autonomic influences. Normally, the activities of the sympathetic and parasympathetic branches of the autonomic nervous system are in dynamic balance indicating healthy and flexible physiological system. The autonomic imbalance – low parasympathetic activity and/or sympathetic overactivity resulting in tachycardia – is common to a broad range of maladaptive conditions and it is associated with the increased risk of cardiovascular adverse outcomes (Friedman, 2007; Porges, 2007; Thayer & Sternberg, 2006).

Prefrontal grey and white matter neurometabolite changes after atomoxetine and methylphenidate in children with attention deficit/hyperactivity disorder: A 1H magnetic resonance spectroscopy study

Attention deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral childhood disorder. Dysfunction of prefrontal neural circuits which are responsible for executive and attentional functions has been previously shown in ADHD. We investigated the neurometablite changes in areas included in dorsolateral prefrontal neural circuits after 2 months of long-acting methylphenidate or atomoxetine medication in children with ADHD who were responders to treatment. Twenty-one ADHD children were examined by single voxel (1)H-magnetic resonance spectroscopy (MRS) before and after 2 months of medication with OROS methylphenidate (n=10) or atomoxetine (n=11). The spectra were taken from the dorsolateral prefrontal cortex (DLPFC, 8ml) and white matter behind the DLPFC (anterior semioval center, 7.5ml), bilaterally. NAA and NAA/Cr (N-acetylaspartate/creatine) decreased in the left DLPFC and Cho/Cr (choline/creatine) increased in the right DLPFC after atomoxetine medication. Glu+Gln and Glu+Gln/Cr (glutamate/glutamine) increased in the left white matter after methylphenidate medication. We hypothesize that atomoxetine could decrease hyperactivation of DLPFC neurons and methylphenidate could lead to increased activation of cortical glutamatergic projections with the consequences of increased tonic dopamine release in the mesocortical system.

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).

A prospective observational study of attention-deficit/hyperactivity disorder in Central and Eastern Europe and Turkey: Symptom severity and treatment options in a paediatric population

Abstract Objective. This study investigates the relationship between treatment regimen, symptom severity, comorbidities and health outcomes of paediatric patients with attention-deficit/hyperactivity disorder (ADHD) in Central and Eastern Europe (CEE). Methods. Males and females aged 6–17 years with ADHD symptoms participated in this 12-month, prospective, observational, non-randomised study. Symptoms and comorbidities were assessed using the Child and Adolescent Symptom Inventory-4 Parent Checklists (CSI-4; ASI-4, categories L/O), and the Clinical Global Impressions-ADHD-Severity scale (CGI-ADHD-S). Baseline data are presented. Results. The study included 566 patients from Czech Republic, Hungary, Romania, Slovakia and Turkey. Psychiatrists made all diagnoses using The American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV), World Health Organization International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10), and “other” criteria (73, 27 and 0.4%, respectively). Patients were grouped into two cohorts based on whether they were prescribed psycho- and/or pharmacotherapy (n=443) or not (n=123). Patients receiving prescribed treatment were older and demonstrated higher symptom severity scores than those receiving no or “other” treatment. Most patients were prescribed conventional treatment for ADHD at baseline. Conclusions. Continued assessment of this population may aid the treatment and outcomes of ADHD in CEE.

Anxiety reduction on atomoxetine and methylphenidate medication in children with ADHD

Atomoxetine and methylphenidate are widely used to treat attention‐deficit–hyperactivity disorder (ADHD) with similar effectiveness after 8 weeks of treatment, when atomoxetine has reached its a full effect. Both drugs have also been shown to have an effect on comorbid anxiety. To the best of our knowledge, no study has compared their effect on the dynamics of anxiety symptom reduction. The aim of this study was to compare the medication effect on core and comorbid anxiety symptom dynamics in children with ADHD.