Somatic and endocrinological changes in non medicated ADHD children.

Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed childhood psychiatric disorders and it constitutes a group of developmental disorders, which are characterized by inadequate level of attention, excessive activity and impulsivity. In connection with neurological and endocrinological changes, children with ADHD can show also changes in the growth and development without consequence to the medication. Differences were found especially in higher weight and BMI. Very few studies were done on this topic and the results of the studies are very different, methods are heterogeneous and insufficient. The most serious absence is the much reduced number of anthropometrics and other characteristics and parameters. Studies usually analyse only BMI, height and weight and do not take into account socio-economic characteristics, feeding customs and other important factors. Many studies are done on changes in growth only associated with medical treatment of children ADHD. However changes in the development and growth can be a manifestation of the disorder itself. Authors of this paper review studies which monitor changes in the development of children with ADHD and compare their results.

Red blood cell triiodothyronine uptake as membrane parameter of depression.

We tested the hypothesis considering the role of hypothalamic-pituitary-thyroid axis (HPT), L-triiodothyronine (L-T3) uptake into erythrocytes, and the role of membrane lipids in the development and treatment of affective disorders. Changes in kinetic parameters (V(max), maximal velocity and K(M), apparent Michaelis constant) of L-T3 uptake into red blood cells (RBCs) and changes in membrane fluidity in a group of 24 patients with major depression were measured before treatment and after 1 month of treatment with citalopram. Parameters V(max) and K(M), as well as membrane microviscosity, were significantly increased in depressed patients both before and after treatment in comparison with healthy subjects. We concluded that the function of the membrane transporter for L-T3 in RBC is changed in depression. This change is probably connected with alteration of membrane fluidity and/or transporter-lipid interactions. We did not find any normalization of the measured parameters after 1 month of treatment. The results show the importance of composition and physical properties of the lipid bilayer for transmembrane transport of L-T3 and support the hypothesis that the HPT axis is in depression.

Polymorphisms of dopamine-beta-hydroxylase in ADHD children.

ADHD is a multifactorial disorder clinically characterized by inattentiveness, impulsivity and hyperactivity. The occurrence of this disorder varies between 3 and 6% of the child population, with boys predominating over girls at a ratio of 3 : 1 or more. Dysfunction or imbalance between the dopaminergic and noradrenergic systems of neurotransmitters can play a key role in the ADHD pathophysiology. Alteration of the dopamine/noradrenaline levels can result in hyperactivity. DBH is an enzyme responsible for the conversion of dopamine into noradrenaline. The DBH protein is released in response to stimulation. DBH activity, derived largely from sympathetic nerves, can be measured in human plasma. Patients with ADHD showed decreased activities of DBH in serum and urine. Low DBH levels correlate indirectly with the seriousness of the hyperkinetic syndrome in children (Galvin et al., 1995, 1997). In the DBH gene, the G444A, G910T, C1603T, C1912T, C-1021T, 5'-ins/del and TaqI polymorphisms occur frequently and may affect the function of gene products or modify gene expression and thus influence the progression of ADHD. This article reviews the DBH itself and polymorphisms in the DBH gene that influence the DBH activity in the serum and the CSF level of DBH. All those are evaluated in connection with ADHD.

Biochemical markers and genetic research of ADHD.

ADHD (attention hyperactivity disorder) is a polygenetic disorder with various candidate genes. At this time, more than thirty dopaminergic, noradrenergic, serotonergic and GABA-ergic genes are known. The research of only some candidate genes (DRD4, DAT, DRD5, DBH, 5HTT, HTR1B and SNAP25) brought relatively consistent results confirming the heredity of ADHD syndromes. The results of research of other genes (DRD2, DRD3, MAO, ADR2A, GABA A3, GABA B3) are not clear yet. This paper summarizes the most important genetic data in correlations with biochemical periphery parameters (especially for DBH, HVA, MHPG, serotonin). Hypothetically, certain subgroups of ADHD may be identified by correlation of biochemical characteristics and some candidate genes. The paper discusses some implications for future research. Review.

Changes of dopamine-beta-hydroxylase activity during ontogenesis in healthy subjects and in an experimental model (rats).

In children and adolescents (250 healthy subjects) serum dopamine-beta-hydroxylase (DBH) activity (23.9+/-5.2 to 57.1+/-17.5 micromol/min/ml) increases with the age between 3-10 years, later it decreases approximately by the age of 10-14 years. At the age of 21 to 60 years DBH level is stable. Our study described decreasing DBH activity in adolescents at the age of 10-14 years in the studied sample of healthy persons. Experimental animals (200 Wistar rats, 5-120 days old) show the same trend of enzymatic activity, similarly as in humans. DBH activity in rats is between 0.85+/-0.1 to 2.8+/-0.05 micromol/min/ml. This activity is highest in 5-day-old rats; it decreases till the age of 14 days and increases mainly in 14- to 35-day-old animals. Decrease of DBH activity in rats between 35 to 40 days is significant and corresponds to the reduction of DBH activity in adolescent humans (10-14 years). Adult rats (aged 90-120 days) show a stable DBH activity. DBH activity intermediately decreases in 10- to 14-year-old children. This decrease corresponds to the intermediate developmental changes of electrophysiological parameters (decreasing EEG activity in healthy adolescents occurs in 10-14 years old children). Puberty is coupled with intermediate decreasing of DBH activity in man and also in experimental animals in the period of prominent psychological and physiological changes.

Electrocardiographic dose-dependent changes in prophylactic doses of dosulepine, lithium and citalopram.

Tricyclic antidepressant drugs dosulepine (TCA), serotonin selective reuptake inhibitor (SSRI) and prophylactic agent with antidepressant effect lithium carbonicum (Li) have different cardiovascular side-effects. We compared them in the prophylactic therapy of periodic affective disorder in remission with TCA, SSRI and Li. Our previous papers confirmed the most prominent effects of heart electric field parameters in TCA patients (Slavícek et al., 1998). In the present work we studied for the first time the dose-dependent changes of ECG, body surface potential maps (BSPM - parameter DIAM 30, 40) in 43 TCA dosulepine, 40 SSRI citalopram and 30 Li outpatients (Hamilton scale: HAMDL10; age 40+/-5 years; treated for depressive disorders or bipolar disorders). The daily doses of dosulepine were 50-250 mg, citalopram 20-80 mg, Li plasma levels 0.66+/-0.08 meq/l. The electrocardiogram (ECG), vectorcardiogram (VCG), and BSPM were measured and calculated by the Cardiag 112.1 diagnostic system. The results have shown a relation between the dose of dosulepine and extremum (maximum and minimum) of depolarization isoarea map in dosulepine, but not in citalopram patients. The repolarization BSPM changes were most pronounced in SSRI patients. Lithium in long-term prophylaxy (1-22 years) caused only minimal ECG BSPM changes. The present results correspond with our previous observations.

Electrocardiogram, vectocardiogram and body surface maps in patients with panic disorder.

An increased risk of myocardial ischemic changes was demonstrated in patients suffering from panic disorder (PD). Using classical ECG methods, this risk cannot be evaluated in most patients. We measured the vectocardiogram (VCG) using Frank orthogonal leads and body surface maps (BSM) including 12-lead ECG. In our study of 11 PD patients (2 men, 9 women), without any seizures and pharmacological treatment and without cardiovascular symptoms, we found marked sinus tachycardia (heart rate 90.1 +/- 12.2 min(-1)) and a shorter R-R interval (678 +/- 93.6 ms) than in 27 controls (heart rate 73.6 +/- 7.7min(-1), R-R 822.7 +/- 86.4 ms) (5 men, 22 women) (p<0.001). The VCG measured spatial QRS-STT angle was more opened (70.3 +/- 24.5 degrees) than in the control group (49.5 +/- 19.5 degrees) (p<0.05). The maximum (extremum) in depolarization (DIAM max 30, 40) and repolarization (RIAM max 35) of body surface isoarea and isointegral (RIIM max) maps was less positive (p<0.001) and the minimum (DIAM min 40) was less negative than in the controls (p<0.05) even in the period free of a panic attack. Our results showed the changes in the heart electric field parameters occurred in PD patients when compared to the control group.

Citalopram inhibits L-type calcium channel current in rat cardiomyocytes in culture.

Selective serotonine reuptake inhibitors (SSRI) are believed to be less dangerous in the treatment of depressive disorder in comparison with tricyclic antidepressants (TCA) due to their relative lack of cardiotoxicity. Thus, we investigated the effect of citalopram (SSRI) on membrane electrophysiology in rat cardiomyocytes in tissue culture. The results were compared with those from amitriptyline (TCA). The whole-cell configuration patch-clamp technique was used. Both citalopram and amitriptyline exhibited the concentration-dependent inhibition of the L-type calcium channel current (ICa). Citalopram in concentrations of 3 microM and 10 microM inhibited peak calcium current by 2.7% and 8%, respectively. We demonstrated the same potency of citalopram and amitriptyline to inhibit ICa. These observations led us to conclude that citalopram and amitriptyline are drugs, which exhibit a similar potency for causing concentration-dependent inhibition of ICa.

Antidepressant drugs and heart electrical field.

Some antidepressant drugs, especially tricyclic ones--(TCA), have cardiovascular side effects. To compare the effects of antidepressant drugs, the electrocardiogram (ECG), vectorcardiogram (VCG), and body surface maps (BSM) were recorded in psychiatric patients without cardiovascular diseases treated by a) TCA amitriptyline or dosulepin (daily dose 50-200 mg, 22 patients), b) lithium (serum level 0.66 +/- 0.08 meq/l, 21 patients), c) selective serotonine reuptake inhibitor citalopram (daily doses 20-60 mg, 30 patients), and in 23 control patients. In the TCA-treated patients, the heart rate was increased, QT and RR intervals shortened (p < 0.01, antimuscarinic effect). This was not observed in lithium- and citalopram-treated patients. All antidepressants decreased the absolute maximum values of depolarization isointegral maps, lithium and TCA reduced the initial and citalopram the later phase of depolarization. Citalopram slightly diminished the amplitude of the R wave. The results confirm the antimuscarinic effects of TCA in therapeutic doses and specify the intraventricular effects of antidepressants.

QT dispersion and electrical heart field morphology in patients treated with dosulepin.

The aim of the study was to detect the changes of QT dispersion (QTd) due to cardiotoxicity of tricyclic antidepressant dosulepin. Electrocardiographic and vectorcardiographic recordings were obtained using Cardiag 112.2 diagnostic system from 28 psychiatric outpatients treated with prophylactic doses of dosulepin and compared to those obtained from 37 healthy volunteers. From these recordings following parameters were evaluated: QTd, spatial QRS-STT angle and amplitude of T-wave. The acquired data were correlated with the dosulepin plasma levels using Spearman's rank order correlation test. The average QTd (+/-S.D.) in the dosulepin group was significantly higher (70+/-21 ms) than that in the control group (34+/-12 ms) (P<0.001). Moreover, the correlation between QTd and the dosulepin plasma levels was highly significant (r = 0.7871, P<0.001). Similar results were obtained when QTc dispersion was used. On the contrary, the QRS-STT space angle did not correlate with the dosulepin plasma levels. Furthermore, the T-wave amplitude was not significantly correlated to the QT-interval. Thus we can conclude that the QT dispersion could be used as a simple marker of the dosulepin effect on the myocardium.

QT dispersion estimated from 80 body surface potential map leads and from standard 12-leads ECG in psychiatric patients treated with dosulepin.

The aim of the study was to detect changes of the QT dispersion (QTd) due to cardiotoxicity of tricyclic antidepressant dosulepin. Electrocardiographic and body surface potential mapping (BSPM) recordings were obtained using Cardiag 112.2 diagnostic system from 27 psychiatric outpatients treated with prophylactic doses of dosulepin and compared to those obtained from 37 healthy volunteers. From these recordings the QTd and the dispersion of heart rate-corrected QT interval QTc were evaluated. These parameters were estimated both from 80 BSPM leads and from 12 standard ECG leads. Acquired data were statistically correlated by Spearman rank order correlation coefficient with dosulepin plasma levels. The average QTd evaluated from BSPM leads (+/-SD) in the dosulepin group was significantly higher [70 (+/-21) ms] than that in the control group [34 (+/-12) ms] (P< 0.001). Moreover, the correlation between QTd and the dosulepin plasma level was statistically significant as well (P< 0.001) with the value of correlation coefficient 0.7871. The QTd evaluated from standard 12 ECG leads was increased in dosulepin group as well [46 (+/-18) ms vs. 28 (+/-10) ms - P< 0.05] but we have not found any significant correlation of the QTd with the dosulepin plasma level. According to the above-mentioned results we can conclude that the QTd estimated from BSPM leads (but not that estimated from 12-lead ECG) could be used as a marker of the dosulepin effect on the myocardium.

[Stimulants]. / Stimulancia.

The authors present a comprehensive account of stimulants from chemical structure to clinical use. They analyze in detail the function and pharmacokinetic properties of stimulants but also their clinical and undesirable side-effects. The section on the interaction of stimulants and other drugs and other types of treatment is very important. The second part of the paper deals with indications and contraindications of stimulants, incl. the possible risk of the development of dependence. There are many indications for stimulants in clinical (in particular paedopsychiatric) practice.

[Attention deficit in hyperactive children]. / Deficit pozornosti u hyperaktivních detí.

The most typical features of hyperactivity in children (ADHD) are deficient attention, impulsiveness and hyperactivity on which the present paper is focused. With this problem symptoms are associated such as sensomotor problems, intellectual questions, impaired sleep, emotional disorders and behavioural disorders. The part devoted to etiology analyzes the impact of the environment and of genetic factors on ADHD whereby the latter factor is dominant. As regards treatment, the authors discuss not only pharmacological treatment, but also counselling for parents and teachers of thus affected children.

[Effect of Aponeuron in the treatment of children with hyperkinetic syndrome]. / Sledování ucinku Aponeuronu v lécbe detí s hyperkinetickým syndromem.

The submitted original paper deals with hyperactivity of children (ADHD) and their treatment by means of the stimulant Aponeuron. The authors made a long-term, double blind, placebo controlled trial which comprised more than 20 hyperactive children. The applied methods are described in detail and the results of individual investigations are summarized. Moreover it is a subject to which in the local professional literature, contrary to that in other countries, little attention was paid, although it is a frequent disorder. Administration of Aponeuron (and stimulations in general) proved useful in the treatment of this disorder. The subtle and crude motorics improved, symptoms of hyperactivity disappeared and the general school performance of the child improved.

Sleep microstructure is not altered in children with attention-deficit/hyperactivity disorder (ADHD).

The high rate of occurrence of sleep disturbances in children with attention-deficit/hyperactivity disorder (ADHD) prompted the idea that structural and neurotransmitter changes might give rise to specific sleep pattern abnormalities. The aim of this study was to evaluate the microstructure of sleep in children with ADHD who had no polysomnographically diagnosed sleep disorder, had never been treated for ADHD, and were free from any psychiatric comorbidity. Participants were 14 patients with ADHD (12 boys and 2 girls aged 7-12 years, mean age 9.6+/-1.6). ADHD was diagnosed according to DSM-IV criteria (Diagnostic and statistical manual of mental disorders). Psychiatric comorbidities were ruled out by detailed psychiatric examination. The patients underwent two consecutive overnight video-polysomnographic (PSG) recordings, with the sleep microstructure (cyclic alternating pattern - CAP) scoring during the second night. The data were compared with age- and sex-matched controls. Sleep microstructure analysis using CAP revealed no significant differences between the ADHD group and the controls in any of the parameters under study. In conclusions, no ADHD-specific alterations were found in the sleep microstructure.

[Neuroleptics in the treatment of schizophrenia in childhood]. / Neuroleptika v lécbe schizofrenie detského veku.

In 40 patients with the diagnosis of schizophrenia, aged 4-15 years, the author revealed markedly more frequently than in adults autistic, catatonic, obsedant, pseudoneurasthenic and depressive symptoms. For treatment incisive as well as inhibitory neuroleptics are used. Some patients with negative symptoms respond favourably to pimozide. In half the patients there is an obvious trend of chronicity.