M Gerlach

Deutschen Gesellschaft für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie e.V., Würzburg, Bavaria, Germany

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Publications (309)938.91 Total impact

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    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 < 0.001, η (2) = 0.285; plasma concentrations ASD 19.61 ± 7.12 pg/ml, ADHD 8.05 ± 5.49 pg/ml, healthy controls 14.43 ± 9.64 pg/ml). Post hoc analyses showed significantly higher concentrations in children with ASD compared to ADHD (p < 0.001). After Bonferroni correction, there was no significant difference in ASD in comparison with healthy controls (p = 0.132). A significant strong correlation between plasma OT and autistic symptomatology, assessed by the Autism Diagnostic Observation Schedule, was observed in the ASD group (p = 0.013, r = 0.603). Patients with ADHD differed from healthy control children by significantly decreased OT concentrations (p = 0.014). No significant influences of the covariates age, IQ, medication and comorbidity could be seen. Our preliminary results point to a correlation of OT plasma concentrations with autistic symptom load in children with ASD and a modulation of the OT system also in the etiologically and phenotypically overlapping disorder ADHD. Further studies in humans and animal models are warranted to clarify the complex association of the OT system with social impairments as well as stress-related and depressive behavior and whether peripheral findings reflect primary changes of OT synthesis and/or release in relevant areas of the CNS.
    ADHD Attention Deficit and Hyperactivity Disorders 07/2014;
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    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.
    Basal Ganglia. 06/2014;
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    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
    Electrophoresis 04/2014; · 3.26 Impact Factor
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    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 < 0.05). Analysis of covariance (ANCOVA) revealed this result in accordance with significant reductions in BDNF mRNA expression in ASD, observed in the mRNA expression study (F = 3.65; df = 2.43; p < 0.05); neither age nor IQ confounded the result, as indicated by ANCOVA (F = 3.961; df = 2.41; p < 0.05, η (2) = 0.162). Our study projects supported the notion that neurotrophins are involved in the pathophysiology of ASD. Further studies may eventually contribute to the identification of distinct peripheral mRNA expression and protein concentration patterns possibly supporting diagnostic and therapeutic processes.
    Journal of Neural Transmission 02/2014; · 3.05 Impact Factor
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    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.
    Journal of Neural Transmission 11/2013; · 3.05 Impact Factor
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    ABSTRACT: 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 are necessary enabling 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 and 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. Biological significance statement 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; · 5.07 Impact Factor
  • Manfred Gerlach, Edna Grünblatt, Klaus W Lange
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    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;
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    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;
  • Basal Ganglia. 03/2013; 3(1):41.
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    ABSTRACT: OBJECTIVE:: This naturalistic therapeutic drug monitoring (TDM) study aimed to evaluate the relationship between dosage, serum concentration, and clinical outcome in children and adolescents treated with the serotonin reuptake inhibitor sertraline for different indications. METHODS:: Steady-state trough serum concentrations were analyzed in 90 subjects, treated with 25-200 mg sertraline per day. Therapeutic efficacy was assessed by the Clinical Global Impression Improvement subscale and side effects by the Udvalg for Kliniske Undersogelser-Side Effect Rating Scale. RESULTS:: In the study population, children were administered higher body weight normalized daily doses than adolescents. The relationships between sertraline daily dosage and serum concentrations (rs = 0.67, P < 0.0001) as well as between body weight normalized daily doses and serum concentrations (r = 0.62, P < 0.0001) were linear. In the whole patient group, no correlation between serum concentrations and either the therapeutic effect or side effects could be observed, neither significant effects of gender, age, concomitant medications, or smoking habits. When analyzing just the patients with depression, those with side effects had significantly higher sertraline serum concentrations than those without (44.8 ng/mL versus 22.3 ng/mL, P = 0.01). In general, occurrence of side effects was significantly more frequent in patients with psychiatric comedication (37.9%) than those without (11.5%, P = 0.002). DISCUSSION:: As this study has the typical limitations of naturalistic studies, the results should be interpreted cautiously. From the data, it is not possible to suggest an age-specific therapeutic window for children and adolescents. However, as the intraindividual variability of sertraline serum concentrations is known to be low, TDM may certainly help to predict serum concentrations after dose adjustment, to assess pharmacokinetic drug-drug interactions influencing serum concentrations and the patient's compliance, finally allowing for personalizing dose through TDM.
    Therapeutic drug monitoring 02/2013; 35(1):84-91. · 2.43 Impact Factor
  • European Neuropsychopharmacology 10/2012; 22:S123–S124. · 4.60 Impact Factor
  • Dominic J Hare, Manfred Gerlach, Peter Riederer
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    ABSTRACT: Redox-active iron is considered to be an important factor in the pathology and progression of several neurodegenerative disorders, including Parkinson's disease. The various roles of iron in normal physiology and its prevalence in the wider environment present numerous challenges to both accurate measurement and interpretation of brain iron levels. This review will discuss considerations for the analysis of iron in post-mortem samples, including how contamination, sample preparation and methods of analysis may influence results. In addition, several important factors influencing interpretation of iron levels will be considered.
    Journal of Neural Transmission 09/2012; · 3.05 Impact Factor
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    ABSTRACT: There is substantial evidence that olfactory function may serve as biomarker in adult neuropsychiatric disorders, e.g. overall diminished olfaction in Parkinson's disease as parameter for early pre-motor and differential diagnosis. Here, we present data from a systematic literature review in olfactory function in child and adolescent psychiatric disorders and report two unpublished data sets of autism and obsessive-compulsive disorder. The overall number of olfaction studies is low-even after taking into account adult samples. In addition, heterogeneity of findings is high due to methodological limitations such as the use of different olfactory tests and odours targeting the olfactory and/or the trigeminal system and neglecting possible confounders, e.g., intelligence or oto-rhino-laryngological affections. Despite these limitations, there is some indication for specific alterations of olfactory function especially in disorders with dopaminergic pathology (e.g. attention deficit/hyperactivity disorder, autism, schizophrenia, 22q11 deletion syndrome). Dopamine is a relevant modulator of early processes in the olfactory bulb. Our systematic review provides the basis for future confirmatory studies investigating olfaction as putative biomarker in child and adolescent psychiatric disorders. We further propose studies of thorough and elaborate methodological standards in combination with imaging techniques and the investigation of the influence of genetic variation on olfactory function.
    Journal of Neural Transmission 07/2012; · 3.05 Impact Factor
  • Article: Editorial.
    Edna Grünblatt, Jürgen Deckert, Manfred Gerlach
    Journal of Neural Transmission 07/2012; · 3.05 Impact Factor
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    ABSTRACT: It has been suggested that the activation of the serotonin (5-hydroxytryptamine, 5-HT) receptor family 5-HT2, in particular the subtype 5-HT2B, is a key step in the progression of drug-induced valvular heart disease (VHD). However, the localisation of 5-HT2 receptors in human valves have not been reported. Thus, the current study investigated the regional and cellular localization of 5-HT2 receptors in the tricuspid, mitral, aortic and pulmonary heart valves of six humans (n = 24 samples) by immunohistochemistry post-mortem. We found that 5-HT2A and 5-HT2B receptors are present in all examined heart valves, whereas 5-HT2C receptors were either not present or scarcely found. Interestingly, we found a uniform pattern of 5-HT2B receptor numbers in all heart valves examined. Our results confirm patterns reported in echocardiographic investigations in patients with Parkinson’s disease treated with cabergoline and pergolide and suggest that the 5-HT2 receptor located in heart valves may play a role in the drug-induced VHD.
    Basal Ganglia. 07/2012; 2(2):87–90.
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    ABSTRACT: Psychiatric "nosology" is largely based on clinical phenomenology using convention-based diagnostic systems not necessarily reflecting neurobiological pathomechanisms. While progress has been made regarding its molecular biology and neuropathology, the phenotypic characterization of ADHD has not improved. Thus, validated biomarkers, more directly linked to the underlying pathology, could constitute an objective measure for the condition. The task force on biological markers of the World Federation of Societies of Biological Psychiatry (WFSBP) and the World Federation of ADHD commissioned this paper to develop a consensus report on potential biomarkers of ADHD. The criteria for biomarker-candidate evaluation were: (1) sensitivity >80%, (2) specificity >80%, (3) the candidate is reliable, reproducible, inexpensive, non-invasive, easy to use, and (4) confirmed by at least two independent studies in peer-reviewed journals conducted by qualified investigators. No reliable ADHD biomarker has been described to date, but some promising candidates (e.g., olfactory sensitivity, substantial echogenicity) exist. A problem in the development of ADHD markers is sample heterogeneity due to aetiological and phenotypic complexity and age-dependent co-morbidities. Most likely, no single ADHD biomarker can be identified. However, the use of a combination of markers may help to reduce heterogeneity and to identify homogeneous subtypes of ADHD.
    The World Journal of Biological Psychiatry 07/2012; 13(5):379-400. · 3.57 Impact Factor
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    ABSTRACT: Piribedil is a non-ergoline, dopamine D(2)/D(3) receptor agonist with α(2) adrenoceptor antagonist properties that has been used in the treatment of Parkinson's disease (PD). Noradrenergic neurotransmission may be involved in the pathogenesis of dyskinesias induced by chronic treatment with L: -DOPA (3,4-dihydroxyphenylalanine, levodopa), but its role in the in vivo action of piribedil or on different subclasses of abnormal involuntary movements (AIMs) remains unclear. The aims of this study were therefore (1) to investigate the anti-dyskinetic effects of piribedil on L: -DOPA-induced contralateral turning behaviour, locomotive dyskinesias (LD), axial dystonia (AD), orolingual dyskinesia (OD) and forelimb dyskinesia (FD) and (2) to compare these effects to the α(2) adrenoceptor antagonist, idazoxan, or the α(2) adrenoceptor agonist, clonidine. Rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and injected intraperitoneally twice daily with L: -DOPA methylester (12.5 mg/kg) and benserazide (3.25 mg/kg). After 3 weeks, the effects of piribedil (5, 15, 40 mg/kg), clonidine (0.15 mg/kg), idazoxan (10 mg/kg) and combinations of these drugs were scored during 2 h. Pre-treatment with 5 and 40 mg/kg, but not 15 mg/kg, of piribedil reduced turning behaviour and AD, OD and FD, but piribedil increased LD at the 40 mg/kg doses compared to the L: -DOPA group. Idazoxan induced similar effects as piribedil (40 mg/kg), except that it had no effect on LD. Idazoxan blocked the effect of piribedil on AD and FD. Clonidine reduced all AIMs except OD, possibly because of its sedative effect. Clonidine blocked the effect of piribedil on AD, OD and FD. These data suggest a differential involvement of α(2) adrenergic receptors in the action of piribedil on different subclasses of L: -DOPA-induced dyskinesias.
    Journal of Neural Transmission 05/2012; · 3.05 Impact Factor
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    ABSTRACT: Attention-deficit hyperactivity disorder (ADHD) is a common behavioural disorder that affects not only children and adolescents but also adults; however, diagnosis of adult ADHD is difficult because patients seem to have reduced externalized behaviour. ADHD is a multifactorial disorder in which many genes, all with small effects, are thought to cause the disorder in the presence of unfavourable environmental conditions. Therefore, in this pilot study, we explored the expression profile of a list of previously established candidate genes in peripheral blood samples from adult ADHD subjects (n = 108) and compared these results with those of healthy controls (n = 35). We demonstrate that combining the gene expression levels of dopamine transporter (SLC6A3), dopamine D5 receptor, tryptophan hydroxylase-1, and SNAP25 as predictors in a regression model resulted in sensitivity and specificity of over 80 % (ROC: max R(2) = 0.587, AUC = 0.917, P < 0.001, 95 % CI: 0.900-0.985). In conclusion, the combination of these four genes could represent a potential method for estimating risk and could be of diagnostic value for ADHD. Nevertheless, further investigation in a larger independent population including different subtypes of ADHD (inattentive, hyperactive, or combined type) patients is required to obtain more specific sets of biomarkers for each subtype as well as to differentiate between child, adolescent, and adulthood forms.
    ADHD Attention Deficit and Hyperactivity Disorders 05/2012; 4(2):77-84.

Publication Stats

6k Citations
938.91 Total Impact Points

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  • 2002–2014
    • Deutschen Gesellschaft für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie e.V.
      Würzburg, Bavaria, Germany
    • Vivantes Klinikum Neukölln
      Berlín, Berlin, Germany
  • 1970–2014
    • University of Wuerzburg
      • • Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy
      • • Department of Psychiatry, Psychosomatics, and Psychotherapy
      • • Institute of Organic Chemistry
      • • Institute for Virology and Immune Biology
      • • Department of Neurology
      Würzburg, Bavaria, Germany
  • 2006–2013
    • University of Zurich
      Zürich, Zurich, Switzerland
  • 2012
    • University of Rostock
      • Klinik und Poliklinik für Psychiatrie und Psychotherapie
      Rostock, Mecklenburg-Vorpommern, Germany
    • University of Technology Sydney 
      • Elemental Bio-Imaging Facility
      Sydney, New South Wales, Australia
  • 2011–2012
    • Universität Regensburg
      • Lehrstuhl für Psychiatrie und Psychotherapie
      Regensburg, Bavaria, Germany
    • Johannes Gutenberg-Universität Mainz
      Mayence, Rheinland-Pfalz, Germany
  • 1991–2012
    • Ruhr-Universität Bochum
      • • Neurologische Klinik
      • • Arbeitsgruppe Klinische Psychologie und Psychotherapie
      • • Medizinisches Proteom-Center
      Bochum, North Rhine-Westphalia, Germany
  • 2009–2011
    • Universität Ulm
      • Clinic of Child and Adolescent Psychiatry/ Psychotherapy
      Ulm, Baden-Wuerttemberg, Germany
  • 2007
    • Actelion Pharmaceuticals Ltd
      Allschwil, Basel-Landschaft, Switzerland
  • 2004–2006
    • Medical University of Silesia in Katowice
      • Department of Instrumental Analysis
      Catowice, Silesian Voivodeship, Poland
    • Technische Universität Dresden
      • Abteilung Neuroradiologie
      Dresden, Saxony, Germany
    • University of Lausanne
      • Department of Psychiatry
      Lausanne, VD, Switzerland
  • 2000–2006
    • University of New South Wales
      • Prince of Wales Medical Research Institute
      Kensington, New South Wales, Australia
  • 2000–2004
    • Max Planck Institute for Experimental Medicine
      Göttingen, Lower Saxony, Germany
  • 1996–2001
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
  • 1999
    • Ludwig-Maximilians-University of Munich
      München, Bavaria, Germany
  • 1983
    • Bielefeld University
      Bielefeld, North Rhine-Westphalia, Germany