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Ehlis A.-C.,University of Wurzburg | Ehlis A.-C.,TU Dresden | Ehlis A.-C.,University of Tubingen | Pauli P.,University of Wurzburg | And 9 more authors.
World Journal of Biological Psychiatry | Year: 2012

Objectives. One of the neurobiological core features of schizophrenic illnesses is a hypo-functionality of the frontal cortex ("cerebral hypofrontality"). The two major classes of antipsychotic medication differ regarding their impact on frontal lobe function and metabolism, with a presumably more positive effect of "atypical" compared to "typical" agents. To date, neurobiological markers reliably predicting the treatment response to different antipsychotics are lacking. The present study, therefore, aimed at establishing a neurophysiological marker of frontal lobe function (NoGo-Anteriorization, NGA) as a predictor of the treatment response to first-and second-generation antipsychotics. Methods. Seventy-six schizophrenic patients were examined three times over a 6-week study period. Patients were treated with first-or second-generation antipsychotics, and NGA, neurocognitive performance, and symptomatology were assessed on admission as well as during two follow-up measurements. Results. Baseline NGA values significantly predicted the treatment response to typical and atypical antipsychotics; however, the direction of this prediction was dependent on the antipsychotic drug regimen. Moreover, atypical antipsychotics had a superior impact on neurocognitive performance and self-reported quality of life. Conclusions. The NGA might be a useful tool in developing individualized treatment strategies based on pathophysiological aspects of schizophrenic illnesses that can be easily determined in clinical routine settings. © 2012 Informa Healthcare.

Englisch S.,Central Institute of Mental Health CIMH | Zink M.,Central Institute of Mental Health CIMH
Mens Sana Monographs | Year: 2012

Treatment-resistant symptoms complicate the clinical course of schizophrenia, and a large proportion of patients do not reach functional recovery. In consequence, polypharmacy is frequently used in treatment-refractory cases, addressing psychotic positive, negative and cognitive symptoms, treatment-emergent side effects caused by antipsychotics and comorbid depressive or obsessive-compulsive symptoms. To a large extent, such strategies are not covered by pharmacological guidelines which strongly suggest antipsychotic monotherapy. Add-on strategies comprise combinations of several antipsychotic agents and augmentations with mood stabilizers; moreover, antidepressants and experimental substances are applied. Based on the accumulated evidence of clinical trials and meta-analyses, combinations of clozapine with certain second-generation antipsychotic agents and the augmentation of antipsychotics with antidepressants seem recommendable, while the augmentation with mood stabilizers cannot be considered superior to placebo. Forthcoming investigations will have to focus on innovative pharmacological agents, the clinical spectrum of cognitive deficits and the implementation of cognitive behavioral therapy.

von der Goltz C.,Central Institute of Mental Health CIMH | Koopmann A.,Central Institute of Mental Health CIMH | Dinter C.,Central Institute of Mental Health CIMH | Richter A.,Central Institute of Mental Health CIMH | And 7 more authors.
Psychoneuroendocrinology | Year: 2010

Objective: Preclinical data suggest modulating effects of both orexin/hypocretin and leptin on dopaminergic transmission in mesolimbic reward pathways. This indicates a possible role of both peptides in reward function and motivation, and thus in addictive diseases. The aim of this study was to examine the possible association between orexin and leptin, and nicotine craving in smokers in a clinical case-control study under standardized conditions. Methods: We compared orexin and leptin, ACTH and cortisol plasma concentrations (RIA) between tobacco smokers (n=60) during early nicotine withdrawal and healthy controls (n=64). Motivational aspects of nicotine craving were additionally assessed in the smoking participants using the Questionnaire of Smoking Urges (QSU). Results: As main results we detected a significant negative correlation between orexin plasma concentration and nicotine craving (r=-0.28; p<05), and a positive association between craving and leptin plasma concentration (r=0.29; p<05). Conclusions: Our results show an association between craving for nicotine and plasma concentrations of orexin and leptin suggesting that both peptides interfere with the dopaminergic transmission during nicotine withdrawal in a bidirectional manner and, thus, modulate craving for nicotine. © 2009 Elsevier Ltd.

Richter S.H.,Central Institute of Mental Health CIMH | Richter S.H.,Justus Liebig University | Richter S.H.,University of Munster | Garner J.P.,Purdue University | And 15 more authors.
PLoS ONE | Year: 2011

In animal experiments, animals, husbandry and test procedures are traditionally standardized to maximize test sensitivity and minimize animal use, assuming that this will also guarantee reproducibility. However, by reducing within-experiment variation, standardization may limit inference to the specific experimental conditions. Indeed, we have recently shown in mice that standardization may generate spurious results in behavioral tests, accounting for poor reproducibility, and that this can be avoided by population heterogenization through systematic variation of experimental conditions. Here, we examined whether a simple form of heterogenization effectively improves reproducibility of test results in a multilaboratory situation. Each of six laboratories independently ordered 64 female mice of two inbred strains (C57BL/6NCrl, DBA/2NCrl) and examined them for strain differences in five commonly used behavioral tests under two different experimental designs. In the standardized design, experimental conditions were standardized as much as possible in each laboratory, while they were systematically varied with respect to the animals' test age and cage enrichment in the heterogenized design. Although heterogenization tended to improve reproducibility by increasing within-experiment variation relative to between-experiment variation, the effect was too weak to account for the large variation between laboratories. However, our findings confirm the potential of systematic heterogenization for improving reproducibility of animal experiments and highlight the need for effective and practicable heterogenization strategies. © 2011 Richter et al.

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