Indikationen, Wirkungsweise, Nebenwirkungen und Risiken, Kontraindikationen und Interaktionen werden für die Medikamente zur Behandlung der ADHS im allgemeinen Teil und dann für jedes Arzneimittel spezifisch im Präparateteil beschrieben.

Objectives The influence of food intake on behavioural disorders was already described in the early 20th century. Elimination of individually allergenic food items from individual diets ["oligoantigenic diet" (OD)] showed promise to improve attention-deficit/hyperactivity disorder (ADHD) symptoms. However, only few of the positive results were evaluated by blinded symptom rating. Therefore the present study's purpose was to evaluate the reliability of a non-blinded rating of the ADHD Rating Scale IV (ARS) for the assessment of OD effects in comparison to a blinded rating of the ARS based on pseudonymized video recordings. Methods Ten children (8m/2f) aged 8 to 14 with ADHD according to ICD-10 participated in an uncontrolled, open-label dietary intervention study. Food items, commonly related to intolerances, were eliminated for four weeks. Participants with > 40% improvement in the ARS between T1 (before the diet) and T2 (after the diet) were defined as responders. Nutrients with individual relevance to ADHD symptoms were identified in a following reintroduction phase (T3-T4) lasting 8-16 weeks. The ARS was completed by a non-blinded child and adolescent psychiatrist (T0-T4). Sessions were recorded on video, pseudonymized, and evaluated by three blinded raters. Complete data were captured for eight children. The inter-rater reliability between the non-blinded therapist and every blinded rater was determined by the intra-class correlation coefficient (ICC). Correlations according to Pearson and Spearman between the non-blinded and blinded rating were calculated for each rater. Results Two blinded raters and the non-blinded rater considered 5 of 8 (62.5%) children as responders, whereas one blinded rater disagreed as to the success of one case thus considering only 4 of 8 children as responders to the diet. Inter-rater reliability was assessed after each rater having scored 33 videos: The intra-class coefficients were >.9 for all raters (rater 1:ICC=.997, rater 2:ICC=.996, rater 3:ICC=.996) and the Spearmanrhobetween the raters were high (n=33; rater 1:rho=.989,p<.0001, rater 2:rho=.987,p<.0001, rater 3:rho=.984,p<.0001), respectively. Discussion As both, blinded and non-blinded ratings of the ARS, revealed relevant significant improvement of ADHD scores in children following an OD in this uncontrolled trial, Randomized controlled trials appear as highly desirable in order to replicate these improvements and to establish reliable and unbiased effect sizes thereby fostering further more objective confirmatory measurements.

Objectives: Psychiatric disorders, such as schizophrenia and other neuroinflammatory diseases are accompanied by an increase in the oxidative stress and changes in the immune system and in the metabolic, hormonal and neurological components of the central nervous system (CNS). Hydrogen sulfide (H2S) is a gaseous molecule that is endogenously produced in the peripheral and central nervous system through cysteine by the following major H2S producing enzymes in the brain: cystathionine-γlyase (CSE), cystathionine ß-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (MPST). The physiological effects of H2S are broad, with antioxidative properties being a major role in the body. The aims of our investigation were to analyze the central nervous antioxidant, metabolic and neuronal effects in the hippocampus of the rat after inflammatory peripheral lipopolysaccharide (LPS) treatment; and to examine the effects of antipsychotics on the expression of these enzymes in human cell lines. Material and Methods: Male Lewis rats (250 g) received an i.p. LPS injection (1 mg/kg) 24 h before microdialysis experiments. Conscious rats were infused via these probes (1.5 μl/min) with a radical scavenger 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH) in Krebs-Ringer solution. Sodiumhydrogensulfide (NaHS, 10 μg/min) was infused after a 2- h baseline for 1 h. Corticosterone, glutamate, glucose and lactate were measured by Elisa. Reactive oxygen species (ROS) were detected by electron spin resonance spectroscopy (ESR). The impact of the antipsychotics haloperidol, clozapine, olanzapine and risperidone on the expression of genes encoding the key enzymes of H2S synthesis was studied at the human neuroblastoma SH-SY5Y and monocytic U-937 cell lines. The cells were incubated for 24 h with 30 μM antipsychotic following which mRNA levels were measured by polymerase chain reaction. Results: Microdialysate glucose and lactate levels dramatically increased in the hippocampus of LPS untreated rats by local application of NaHS. By contrast, in the LPS pretreated rats, there was no effect of NaHS infusion on glucose but a further significant increase in microdialysate lactate was found. It was LPS pretreatment alone that particularly enhanced lactate levels. There was a marked increase in hippocampal microdialysate glutamate levels after local NaHS infusion in LPS untreated animals. In LPS treated rats, no change was observed by NaHS, but LPS itself had the strongest effect on microdialysate glutamate levels. Microdialysate corticosterone levels were reduced by NaHS in both LPS pretreated and untreated rats. The formation of free radicals in the hippocampus significantly reduced in LPS pretreated rats, while in LPS untreated rats a significant increase was observed after NaHS infusion. In human SH-SY5Y and U-937 cells, all three major enzymes of H2S-Synthesis, namely cystathionine-γ-lyase, cystathione ß-synthase and 3-mercaptopyruvate sulfurtransferase, could be detected by PCR. The antipsychotics haloperidol, clozapine, olanzapine and risperidone affected all three enzymes in different ways; with haloperidol and risperidone showing major effects that led to reductions in CBS or CSE expression. Discussion: The local application of NaHS in the hippocampus of the rat strongly affected glucose, lactate and glutamate release. Contrastingly, in LPS pretreated rats, a decreased radical formation was the only effect found. H2S synthetizing enzymes may be involved in antipsychotic mechanisms, although no clear common mechanism could be found.

Synthetic Substance P analogs where each of the first five peptide bonds are replaced by the peptide bond surrogate GlyΨ[CH2CH2]Gly are investigated as ligands to the Neurokinin 1 (NK1) receptor from rat cerebral cortex. The affinities of these analogs are then compared with the corresponding Gly-Gly analogs. With this model system replacement of the peptide bond between position 4 and 5 with Ψ[CH2CH2] resulted in a 7-fold reduction of affinity. Substitution of other peptide bonds resulted in only minor changes in affinity.Although the N-terminal hexapeptide is important for high affinity binding to the NK1 receptor the present study provides evidence for that this effects is not caused by the side chains of the amino acids in position 1–6 or as results of intramolecular hydrogen bonding with the C-terminal part of the peptide. A possible exception is the peptide bond that in the native peptide connects Pro4 and Gln5.

Indices from a more elementary neuropsychological level might be useful in the search for genes for complex psychiatric disorders, such as ADHD. In this study we investigated systematically whether attentional performance as measured with the Attention Network Test (ANT) is suited for the identification of endophenotypes of ADHD. Attentional performance in affected sib pairs with ADHD (n = 181) was compared to unaffected control siblings (n = 121). Intrafamilial correlation patterns were calculated. In addition, linkage and association analyses were conducted between quantitative scores of attentional functions and dopamine receptor D4 (DRD4) and dopamine transporter (DAT1 or SLC6A3) gene variants. Only the executive attention network was significantly impaired in subjects with ADHD compared to controls (P < 0.05) and showed evidence for familiality in both affected and unaffected families. Linkage analyses revealed the highest LOD score for a severity score based on DSM‐IV inattentive symptoms in the DAT1 chromosomal region (LOD score 2.6 at 15 cM). However, a SNP (rs6350) at the DAT1 locus showed a tendency for association with both alerting performance (P = 0.02) and executive attention (P = 0.01) although it did not survive alpha adjustment for multiple testing. No evidence was found for association of any of the investigated phenotypes with the VNTR in the DRD4. Thus, our data suggest that the quantitative behavioral ratings of inattentive symptoms might be more useful when searching for new genes associated with ADHD, however, among the ANT measures the executive attention network seems to be best suited for further endophenotype analyses. © 2009 Wiley‐Liss, Inc.

Because there are reports on cytotoxic and cytoprotective effects of antipsychotics, the aim of the present study was to evaluate the impacts of different concentrations (1.6—50 μg/mL) of atypical antipsychotics on the survival of human neuronal (neuroblastoma SH-SY5Y) and immune (monocytic U-937) cells and on energy metabolism (ATP level after the incubation with antipsychotics in the concentration of 25 μg/mL). Statistical analysis showed that incubation for 24 h with the antipsychotics quetiapine, risperidone, 9-hydroxyrisperidone and ziprasidone led to a significantly enhanced cell survival in both cell lines in the lower concentrations. Higher concentrations exerted in part cytotoxic effects with the exception of quetiapine, but therapeutically relevant concentrations of the drugs were not cytotoxic in our experiments. Measurement of ATP contents in the neuronal cell line showed significantly increased levels after a 24-h treatment with 25 μg/mL risperidone and 9-hydroxyrisperidone. The other substances produced no effects. Our results show that the antipsychotic substances under investigation exert concentration-dependent effects on cell survival in both cell lines examined.

Plant extracts such as Hypericum perforatum and Pycnogenol® have been tested as alternatives to the classical ADHD drugs. It has been possible to describe neuroprotective effects of such plant extracts. A reduction of ADHD symptoms could be shown in clinical studies after the application of Pycnogenol®, which is a pine bark extract. The impacts of the standardized herbal extracts Hypericum perforatum, Pycnogenol® and Enzogenol® up to a concentration of 5000 ng/mL on cell survival and energy metabolism in human SH‐SY5Y neuroblastoma cells has been investigated in the present examination. Hypericum perforatum significantly decreased the survival of cells after treatment with a concentration of 5000 ng/mL, whereas lower concentrations exerted no significant effects. Pycnogenol® induced a significant increase of cell survival after incubation with a concentration of 32.25 ng/mL and a concentration of 250 ng/mL. Other applied concentrations of Pycnogenol® failed to exert significant effects. Treatment with Enzogenol® did not lead to significant changes in cell survival.

There is evidence that reactive oxygen species (ROS) are involved in the pathophysiology of psychiatric disorders such as schizophrenia. Indirect biochemical alterations of ROS formation have been shown for patients treated with antipsychotics as well as for untreated patients. Only one study measured directly the ROS formation after treatment with antipsychotics by using electron spin resonance spectroscopy. The aim of the present examination was to demonstrate the effects of haloperidol, clozapine and olanzapine in concentrations of 18, 90 and 180 μg/mL on the formation of ROS in the whole blood of rats by using electron spin resonance spectroscopy after incubation for 30 min. To test the protective capacity of vitamin C we incubated the highest concentration of each drug with vitamin C (1 mM). Under all treatment conditions, olanzapine led to a significantly higher formation of ROS compared with control conditions, whereas in the cases of haloperidol and clozapine the two higher concentrations induced a significantly enhanced formation of ROS. Vitamin C reduced the ROS production of all drugs tested and for haloperidol and clozapine the level of significance was reached. Our study demonstrated that antipsychotics induce the formation of ROS in the whole blood of rats, which can be reduced by the application of vitamin C.