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The present article provides a review of a series of studies in children with attention deficit hyperactivity disorder (ADHD) concerning (1) the effects of methylphenidate on various attentional functions, (2) the stimulant-induced changes of both qualitative and quantitative (i.e. kinematic) aspects of handwriting, (3) the interaction between conscious control of handwriting and fluency of handwriting movements, and (4) possible therapeutic approaches to graphomotor disturbances. Children with ADHD showed impairments in various aspects of attentional functioning. Pharmacological treatment of ADHD children with methylphenidate resulted in marked improvements of various components of attentional functioning. In comparison to the performance following the withdrawal of methylphenidate, children with ADHD on methylphenidate displayed a significant improvement in task accuracy in the areas of vigilance, divided attention, selective attention (inhibition, focused attention and integration of sensory information) and flexibility. However, the comparison with healthy children revealed considerable deficits regarding vigilance, divided attention, flexibility and selective attention (focused attention and integration of sensory information) in children with ADHD on methylphenidate. The comparison of writing movements of children on and off methylphenidate revealed that medication resulted in a better handwriting, but a deterioration in handwriting fluency as assessed by kinematic analysis.

Therapeutic Drag Monitoring (TDM) is a tool to optimise antidepressant pharmacotherapy improving efficacy and avoiding side effects. The Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP)-TDM group has worked out consensus guidelines to make progress in the use of TDM which in spite of its obvious advantages, is far from optimal in everyday clinical practice. Research-based levels of recommendation were defined with regard to routine monitoring of plasma concentrations for dose titration. Main indications of TDM compromise control of compliance, lack of clinical response or adverse effects at recommended doses, drag interactions, pharmacovigilance programs, presence of a genetic predisposition particularity concerning the drug metabolism, children, adolescents and elderly patients. Therapeutic ranges of plasma concentrations that are considered to be optimal for treatment are proposed, implications on pharmacoeconomics aspects are discussed. The need to improve the implementation of TDM in routine patient care is emphasized.

This overview presents a hypothesis to bridge the gap between psychoneuroimmunological findings and recent results from pharmacological, neurochemical and genetic studies in schizophrenia. In schizophrenia, a glutamatergic hypofunction is discussed to be crucially involved in dopaminergic dysfunction. This view is supported by findings of the neuregulin- and dysbindin genes, which have functional impact on the glutamatergic system. Glutamatergic hypofunction is mediated by NMDA ( N -methyl-D-aspartate) receptor antagonism. The only endogenous NMDA receptor antagonist identified up to now is kynurenic acid (KYN-A). KYN-A also blocks the nicotinergic acetycholine receptor, i.e. increased KYN-A levels can explain psychotic symptoms and cognitive deterioration. KYN-A levels are described to be higher in the CSF and in critical CNS regions of schizophrenics.

Abnormal glutamate neurotransmission has been implicated in the pathophysiology of schizophrenia. In the present study we investigated two potential neuronal glutamatergic markers, the Excitatory Amino Acid Transporter 3 (EAAT3) and the Vesicular Glutamate Transporter 1 (VGluTl), in post-mortem striatal tissue from control subjects and from subjects with schizophrenia ( n = 15 per group). We also investigated the possible influence of chronic antipsychotic administration (typical and atyp ical) on striatal VGluTl expression in the rat brain. We found deficits in EAAT3 in all striatal regions examined in schizophrenia when compared to controls. Following correction for confounding factors (post-mortem interval), these deficits only remained significant in the caudate nucleus (p = 0.019). We also found significant deficits in VGluTl in the caudate nucleus (p = 0.009) in schizophrenia. There were no significant differences in VGluTl in the striatum of antipsychotic treated rats when compared to their vehicle treated controls.

Data about therapeutic drag monitoring (TDM) of psychotro pic medications are often obtained from samples of highly selected individ uals, who may not be representative for the average psychiatric patient. These data therefore may have limitations with regard to their transferability to everyday clinical practice. Therefore studies under naturalistic conditions are important to clarify the full clinical relevance of TDM. We retrospec tively evaluated all TDM-analyses of the tricyclic antidepressants (TCA) amitriptyline and clomipramine during a 12-month period in an unselected sample of patients in a standard clinical setting. We especially examined the relationship between serum levels on one hand and clinical response and adverse effects on the other hand. In patients with amitriptyline, responders showed a significantly higher serum level than non-responders, whereas in patients with clomipramine a serum level within the recommended therapeutic range was associated with clinical response. We also found significantly higher serum concentrations in patients with adverse effects compared to patients without adverse effects in the clomipramine group. No such relationship could be shown in patients treated with amitrip tyline. Our results suggest that therapeutic ranges in naturalistic set tings in some ways differ from those obtained in controlled clinical settings and that TDM studies in everyday clinical practice are necessary and beneficial.

Background Polymorphisms in the human frizzeled-3 (FZD3) gene have been associated with schizophrenia in an Asian population sample. However, this finding could not be confirmed in subsequent studies investigating other populations. Here we attempted to replicate this finding in a sample of 192 German chronically ill schizophrenic subjects. Methods Three single nucleotide polymorphisms in the FZD3 gene have been genotyped by primer extension and MALDI-TOF measurement. Subsequently, associations for single markers as well as haplotypes were tested. Results In German patients, neither single markers nor haplotypes in FZD3 were associated with schizophrenia. Further exploratory analyses using a different diagnostic approach did also not yield significant results. Conclusions FZD3 is unlikely to play a role in the genetic predisposition towards schizophrenia in the Caucasian population.

The aim of this study was to analyze motor inhibition and facilitation of adult ADHD patients using double pulse transcranial magnetic stimulation (TMS). Twenty-six right handed adult ADHD patients according to DSM-IV were investigated and compared to 26 age and sexmatched controls. In the left hemisphere, mean motor inhibition was 0.53 ±0.33 (mean ±SD) in ADHD patients and 0.34 ±0.16 (mean ±SD) in controls (p = 0.012). There were no significant differences in motor excitability concerning facilitation or in the right hemisphere. Decreased motor inhibition correlated with a higher symptom score derived from the Wender Reimherr Interview (WRI) (p = 0.28; p = 0.04) and also with self rated hyperactivity/impulsivity symptoms (p = 0.30; p = 0.03). In conclusion, decreased motor inhibition in adult ADHD corroborate similar findings in children with ADHD (Moll et al., 2000) and reflect disturbed impulsivity and hyperactivity on a neurophysiological level.

Methylphenidate (MPH) is a centrally acting (psycho)stimulant which reversibly blocks the dopamine re-uptake transporter. At present MPH is one of the most frequently prescribed drugs for the symptomatic treatment of attention deficit hyperactivity disorder (ADHD). Although MPH has been in use for about 50 years, there is no information available concerning the long-term benefits and risks of medication. Based on experiments in rats it has been suggested that MPH treatment may affect the maturation of central dopaminergic systems and may be a risk factor for the development of Parkinson’s disease (PD). The aim of the present case-control study was to gain information about (1) ADHD-like symptoms that may precede PD motor symptoms, and (2) the exposure to psychostimulants in childhood. We used a German short version of the Wender Utah Rating Scale (WURS-k, Retz-Junginger et al., 2002) which is a reliable measure for the retrospective diagnosis of childhood ADHD, and another questionnaire including a rating scale for symptoms of ADHD in childhood (Q-ADHD-Child) according to DSM-IV and ICD-10 criteria.

In this study we investigated differences in the gene expression profiling of the brains of rhesus macaques that were uninfected or infected with SIV in the asymptomatic stage or AIDS. The main aim was to use biostatistical methods to classify brain gene expression following SIV infection, without consideration of the biological significance of the individual genes. We also used data from animals treated with different pharmacological substances such as dopaminergic drags, N-methyl-D-aspartate (NMDA) antagonists or antioxidants during the early stage of infection as these animals exhibited an accelerated or attenuated neuropsychiatrie disease progression.

Multiple sclerosis (MS) is a chronic, demyelinating disease of unknown origin. Sophisticated analytical methods have made it possible to measure small biologically active molecules at low endogenous levels, and understand their role in the network of other biologically active compounds actively involved in inflammatory and neurodegenerative processes. Evidence is accumulating as concerns the disturbances of the kynurenine pathway and redox changes in MS. A new promising metabolite of the kynurenine pathway seems to beneficially influence experimental allergic encephalomyelitis. More clinical evidence is needed to prove the role of kynurenic acid analogues and/or enzyme inhibitors as potential medications in MS in the future. Various compounds have been shown to be important in the pathophysiological processes of the disease and are targets for pharmaceutical intervention.