[Show abstract][Hide abstract] ABSTRACT: Physicians, caregivers and patients themselves must be alert to the onset of and changes in motor and non-motor features during the course of Parkinson's disease (PD). Parallel laboratory routine assessments are necessary because of the evolving impairment of the general health status of the individual. A number of potential biomarkers for the diagnosis of PD are currently under investigation, with diagnosis early in the disease course a particular goal, even before the onset of motor symptoms. The aim of this guideline article is to provide user-friendly, clinical evidence-based recommendations for using laboratory pathological testing for the diagnosis and differential diagnosis of PD, for assessing its time course, and managing complications of long-term dopaminergic therapy and the disabling motor features that develop in the later stages of the disease.
Journal of Neural Transmission 11/2015; DOI:10.1007/s00702-015-1481-6 · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rational pharmacotherapy is a challenging task in child and adolescent psychiatry. Increasing prescription numbers contrast with the uncertainties of safety and efficacy issues. The lack of clinical (authorization) trials often implies a non- age-specific use of drugs. However, young patients show particular metabolic conditions and a higher vulnerability for adverse drug reactions. Thus it seems mandatory to create age-specific pharmacological data about efficacy and safety of psychotropic drug use in minors. Legislation authorities became aware of this situation and introduced European and national scientific pharmacovigilance regulations and programmes accordingly in order to continuously evaluate the benefit-risk-ratio, detect, collect, minimize, and prevent adverse effects of drugs by appropriate measures, e.g., therapeutic drug monitoring. In this paper the principles and needs of pharmacovigilance in child and adolescent psychiatry are discussed. Furthermore a large multicenter clinical trial («TDM-VIGIL»), funded by the German Federal Institute for Drugs and Medical Devices, is presented, which appeals to collect epidemiological prescription and safety data of psychotropic drugs in children and adolescents using an internet-based data infrastructure (patient registry).
Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie 01/2015; 43(1):21-8. DOI:10.1024/1422-4917/a000329 · 0.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Findings from research in animal models and humans have shown a clear role for the neuropeptide oxytocin (OT) on complex social behaviors. This is also true in the context of autism spectrum disorder (ASD). Previous studies on peripheral OT concentrations in children and young adults have reported conflicting results with the initial studies presenting mainly decreased OT plasma levels in ASD compared to healthy controls. Our study therefore aimed to further investigate changes in peripheral OT concentrations as a potential surrogate for the effects observed in the central nervous system (CNS) in ASD. OT plasma concentrations were assessed in 19 male children and adolescents with ASD, all with an IQ > 70 (age 10.7 ± 3.8 years), 17 healthy male children (age 13.6 ± 2.1 years) and 19 young male patients with attention deficit hyperactivity disorder (ADHD) as a clinical control group (age 10.4 ± 1.9 years) using a validated radioimmunoassay. Analysis of covariance revealed significant group differences in OT plasma concentrations (F(2, 48) = 9.574, p
ADHD Attention Deficit and Hyperactivity Disorders 07/2014; 6(3). DOI:10.1007/s12402-014-0145-y
[Show abstract][Hide abstract] ABSTRACT: Autism spectrum disorder (ASD) diagnosis is increasing, with 1/88 children believed to be affected by the disorder, with a most recent survey suggesting numbers as high as 1/50. Treatment and understanding of ASD causes is a pressing health concern. ASD protein biomarkers may provide clues about ASD cause. Protein biomarkers for ASDs could be used for ASD diagnosis, subtyping, treatment monitoring and identifying therapeutic targets. Here we analyzed the sera from 7 children with ASD and 7 matched controls using Tricine gel electrophoresis (Tricine-PAGE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Overall, we found increased levels of apolipoproteins (Apos) ApoA1 and ApoA4, involved in cholesterol metabolism and of serum paraoxanase/arylesterase 1 (PON1), involved in preventing oxidative damage, in the sera of children with ASD, compared with their matched controls. All three proteins are predicted to interact with each other and are parts of High Density Lipoproteins (HDLs). Further studies are needed to validate these findings in larger subject numbers.This article is protected by copyright. All rights reserved
[Show abstract][Hide abstract] ABSTRACT: Numerous studies have shown that, among other factors, high DDL's constitute a significant risk for the early development of dyskinesias. In a recently published post-hoc analysis of material from the STRIDE-PD study high LDD's >400 mg per day were identified as risk factors for the development of dyskinesias and the question was presented for discussion as to whether daily doses >400 mg should therefore be principally avoided. The present paper reviews the consensus reached at the expert meeting from November, 2013, which critically debated on this recommendation. Evidence based on reliable work on the optimum levodopa dose is meager due to the lack of specifically controlled titration studies and is based mainly on indirect data from clinical comparative studies on levodopa vs. other dopaminergic agents: In early stages of the disease daily doses usually reached 400-600 mg/die, while 700-1400 mg/die were typical in advanced cases, but in all cases the variation was considerable. Seen in this light, the present authors hesitate to support the claim that LDD's should be limited to below 400 mg/die. This claim has not yet been corroborated sufficiently.
[Show abstract][Hide abstract] ABSTRACT: Findings from molecular genetic studies and analyses of postmortem and peripheral tissue led to the hypothesis that neurotrophins—as crucial moderators of neuroplasticity—impact on the pathophysiology of autism spectrum disorder (ASD). The study projects aimed to complement former results on the role of brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family with fundamental impact on brain development and function. The purpose of this work was to investigate peripheral BDNF mRNA expression and BDNF protein concentrations in ASD as potential surrogates for the effects observed in the central nervous system. In a BDNF protein quantification study, serum concentrations were analyzed using Enzyme-Linked Immunosorbent Assays in 24 male patients with ASD, all with an IQ > 70 (age 13.9 ± 3.0 years) and 20 age- and gender-matched healthy control subjects (age 14.4 ± 2.1 years; p = 0.522). In a further independent project, a BDNF mRNA expression analysis, mRNA levels from total blood were assessed by quantitative real-time polymerase chain reaction in a sample of 16 male ASD patients (age 10.8 ± 2.2), 15 age- and gender-matched healthy controls (age 12.1 ± 2.2) and 15 patients with attention deficit hyperactivity disorder as a clinical control group (age 11.8 ± 2.2; p = 0.207). In the protein quantification project, significantly decreased BDNF serum concentrations were found in ASD cases compared to healthy control children (t = −2.123, df = 42, p
[Show abstract][Hide abstract] ABSTRACT: Anxiolytics (synonym, tranquillizers) are antianxiety drugs that are used in the pharmacological treatment of anxiety disorders. Anxiety is rather untypical for psychiatric disorders in that it may occur as both a normal emotional and a pathological state. During early human history, anxiety was probably adaptive and thus a criterion for selection. This may explain the high lifetime prevalence for anxiety states (≥15 % of population; Nutt 2003). Anxiety disorders often first emerge during childhood and adolescence and represent one of the most common forms of psychopathology among children and adolescents. Anxiety disorders include seven major debilitating subtype disorders: separation anxiety disorder, generalized anxiety disorder, social phobia, panic disorder (with and without agoraphobia), agoraphobia without panic disorder, post-traumatic stress disorder, and obsessive-compulsive disorder (OCD).
Psychiatric Drugs in Children and Adolescents, 01/2014: pages 219-255; , ISBN: 978-3-7091-1500-8
[Show abstract][Hide abstract] ABSTRACT: Antidepressants elevate pathologically depressed mood. Some agents may increase activity or dampen psychomotor restlessness. They can provide relief for those suffering from depressive delusions and may diminish the somatic and vegetative symptoms associated with depression. The term "antidepressants" encompasses a chemically and pharmacologically heterogeneous class of psychopharmacological agents that were originally employed primarily in patients with depressive symptoms, but which today find widespread therapeutic application in areas other than depressive disorders. These agents are thus also employed with clinical success in obsessive-compulsive disorder, in generalized anxiety, panic, phobic and eating disorders, as well as in the therapy of mutism and ADHD.
Psychiatric Drugs in Children and Adolescents, 01/2014: pages 83-155; , ISBN: 978-3-7091-1500-8
[Show abstract][Hide abstract] ABSTRACT: The term “psychostimulants” (synonym stimulants) refers to a group of psychopharmacological agents whose predominant effect is the enhancement of cognitive and behavioral functions by stimulation of the central nervous system (CNS). In healthy humans, they relieve feelings of tiredness and languor, elevate mood, as well as improve concentration and performance. In animals, psychostimulants increase locomotor activity and are readily self-administered due to their powerful reinforcing properties.
[Show abstract][Hide abstract] ABSTRACT: Histopathological, biochemical, and in vivo brain imaging techniques have revealed a consistent increase of total iron in the substantia nigra pars compacta (SNc) of Parkinson’s disease (PD) patients. Interestingly, the increased iron was shown to be restricted to the SNc and occurs in the ferric (Fe3+), rather than ferrous (Fe2+), form of the metal. The objective of this chapter is to discuss the evidence for dopaminergic cell death in the rat following unilateral ferric iron injections into the SN. In addition, this chapter will briefly review findings showing that NM-bound ferric iron represents a pool of iron that, under certain circumstances, can be released to interact with free radical-producing pathways and the ubiquitin proteasome system, ultimately leading to dopaminergic nerve cell death in the rat. Special attention will be paid to summarize evidence that iron-induced dopaminergic cell death reproduces key features of PD and mimics molecular mechanisms underlying dopaminergic cell death in PD.
Handbook of Neurotoxicity, 01/2014: pages 2065-2073; , ISBN: 978-1-4614-5835-7
[Show abstract][Hide abstract] ABSTRACT: http://www2.kenes.com/wip2014/abstract/Documents/HIGH%20RES%20-%2020th%20World%20Congress%20on%20Parkinson%27s%20Disease%20and%20Related%20Disorders.pdf
During the progress of Parkinson’s disease (PD) neuromelanin containing dopaminergic neurons of the substantia nigra pars compacta (Snpc) degenerate and synaptic processes are impaired. Using proteomic
techniques we aim to further characterize neuromelanin as well as synaptosomal structures of human Snpc using high-end proteomic and mass spectrometric technologies in order to better understand underlying pathomechanisms leading to PD.
Neuromelanin granules and synaptosomes are enriched as described [1,2] and subsequently used for proteomic/mass spectrometric analysis.
A first differential study was performed comparing neuromelanin granules from healthy control and PD individuals. This revealed several proteins to be regulated differently in healthy controls in comparison to PD individuals e.g., structural proteins involved in axonal growth.
First studies lead to the identification of interesting candidate proteins which may have striking effects on PD progression.
1. Tribl, F., Gerlach, M., Marcus, K., Asan, E., et al., “Subcellular proteomics” of neuromelanin granules isolated from the human brain. Molecular & Cellular Proteomics 2005, 4, 945–957.
2. Plum, S., Helling, S., Theiss, C., Leite, R.E.P., et al., Combined enrichment of neuromelanin granules and synaptosomes from human substantia nigra pars compacta tissue for proteomic analysis. Journal of Proteomics (in press).
20 th World Congress on Parkinson’s Disease and Related Disorders, Geneva, Switzerland; 12/2013
[Show abstract][Hide abstract] ABSTRACT: Patients with Parkinson's disease receive selective irreversible monoamine oxidase (MAO)-B inhibitors, but their effects on MAO-A activity are not known during long-term application. We determined MAO-A inhibition in plasma samples from patients with MAO-B inhibitor intake or without MAO-B inhibitor treatment and from healthy controls. We detected a 70 % reduction of MAO-A activity in patients with MAO-B inhibitor therapy in comparison to the other groups. Our results suggest that treatment with MAO-B inhibitor may also influence MAO-A activity in vivo, when administered daily.
[Show abstract][Hide abstract] ABSTRACT: Unlabelled:
This article gives a detailed description of a protocol using density gradient centrifugation for the enrichment of neuromelanin granules and synaptosomes from low amounts (≥0.15g) of human substantia nigra pars compacta tissue. This has a great advantage compared to already existing methods as it allows for the first time (i) a combined enrichment of neuromelanin granules and synaptosomes and (ii) just minimal amounts of tissue necessary to enable donor specific analysis. Individual specimens were classified as control or diseased according to clinical evaluation and neuropathological examination. For the enrichment of synaptosomes and neuromelanin granules from the same tissue sample density gradient centrifugations using Percoll® and Iodixanol were performed. The purity of resulting fractions was checked by transmission electron microscopy. We were able to establish a reproducible and easy to handle protocol combining two different density gradient centrifugations: using an Iodixanol gradient neuromelanin granules were enriched and in parallel, from the same sample, a fraction of synaptosomes with high purity using a Percoll® gradient was obtained. Our subfractionation strategy will enable a subsequent in depth proteomic characterization of neurodegenerative processes in the substantia nigra pars compacta in patients with Parkinson's disease and dementia with Lewy bodies compared to appropriate controls.
Key features of Parkinson's disease are the degeneration of dopaminergic neurons in the substantia nigra pars compacta, an associated loss of the brain pigment neuromelanin and a resulting impairment of the neuronal network. The accumulation of iron binding neuromelanin granules is age- and disease-dependent and disease specific alterations could affect the neuronal iron homeostasis leading to oxidative stress induced cell death. The focus of the described method is the analysis of neuromelanin granules as well as axonal cell-endings of nerve cells (synaptosomes) of individual donors (control and diseased). It is the basis for the identification of disease-relevant changes in the iron homeostasis and the generation of new insight into altered protein compositions or regulations which might lead to disturbed communications between nerve cells resulting in pathogenic processes.
Journal of proteomics 08/2013; 94. DOI:10.1016/j.jprot.2013.07.015 · 3.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A major concern regarding psychostimulant medication (amphetamine and methylphenidate) in the treatment of children and adolescents with attention deficit/hyperactivity disorder (ADHD) are the potential adverse effects to the developing brain, particularly in regard to dopaminergic brain function. The present review focuses on the pharmacology of these psychostimulants, their mode of action in the human brain and their potential neurotoxic effects to the developing brain in animals, particularly concerning DA brain function. The potential clinical significance of these findings for the treatment of ADHD in children and adolescents is discussed. Studies on sensitization to psychostimulants' rewarding effects, which is a process expected to increase the risk of substance abuse in humans, are not included. The available findings in non-human primates support the notion that the administration of amphetamine and methylphenidate with procedures simulating clinical treatment conditions does not lead to long-term adverse effects in regard to development, neurobiology or behaviour as related to the central dopaminergic system.
ADHD Attention Deficit and Hyperactivity Disorders 04/2013; 5(2). DOI:10.1007/s12402-013-0105-y
[Show abstract][Hide abstract] ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) has been associated with alterations in iron metabolism, and low ferritin concentrations in peripheral blood have inconsistently been reported in clinically referred samples of children with ADHD. This study examined whether higher peripheral concentrations of ferritin, the major iron storage protein, are associated with decreased symptoms of ADHD in 2,805 children aged 10 years participating in two large population-based birth cohorts (GINIplus and LISAplus). Whether high ferritin concentrations at age 4 months predict lower ADHD symptoms at age 10 years was also investigated using a longitudinal approach in a subsample of 193 children. No indications for an association between peripheral ferritin concentrations and ADHD symptoms were found in this large population-based study. Re-evaluating iron substitution as a therapeutic measure for ADHD may be warranted.
ADHD Attention Deficit and Hyperactivity Disorders 04/2013; 5(3). DOI:10.1007/s12402-013-0108-8