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Wolfgang Gaebel,
Mathias Riesbeck,
Wolfgang Wölwer,
Ansgar Klimke,
Matthias Eickhoff,
Martina von Wilmsdorff,
Isabella Heuser,
Wolfgang Maier,
Joachim Klosterkötter, Peter Falkai,
Ralf Schlösser,
Andrea Schmitt,
Michael Riedel,
Stefan Klingberg,
Wolfgang Köpcke,
Christian Ohmann,
Hans-Jürgen Möller
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ABSTRACT: OBJECTIVE: Full and sustained symptom remission is a major treatment objective after a first-episode in schizophrenia. Findings regarding differences in remission between first- and second-generation antipsychotics are inconclusive. This study aimed to provide rates and predictors of remission in first-episode schizophrenia and to identify symptoms that prevent remission. METHODS: Prevalence rates of "symptomatic remission" (symptom criteria only) and "enduring remission" (symptom and 6-month time criteria), defined according to Andreasen et al. (2005), were determined in first-episode patients participating in a RCT by the German Research Network on Schizophrenia (GRNS) that compared post-acute, 1-year maintenance treatment with risperidone or haloperidol. Respective predictors at baseline were identified by logistic and Cox regression analysis. RESULTS: Prevalence rates were 91.5% for symptomatic remission (n=152/166 eligible patients) and 58.6% for enduring remission (n=65 of 111 patients who continued for at least 6months; 39.2% of all 166 patients included), with no significant differences between risperidone and haloperidol in either type of remission. Enduring remission often was not reached because of negative symptoms: After 6months, 40.5% of the patients had at least 1 negative symptom, whereas only 10.8% of the patients had "persisting" positive symptoms. Of the different predictors identified in univariate analyses, (lower) negative symptoms and participating in standardized psychological treatment remained significant in multivariate (stepwise forward) analyses for enduring remission. CONCLUSIONS: By far most of the first-episode patients reached a temporary state of full symptomatic remission within 1year of antipsychotic treatment. However, only about 50% achieved sustained, enduring remission. Negative symptoms are still a major treatment obstacle to enduring remission in schizophrenia.
Biological Psychiatry 05/2013; · 8.28 Impact Factor
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Archiv f ur Psychiatrie und Nervenkrankheiten 04/2013; · 2.75 Impact Factor
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ABSTRACT: Evidence suggests that the anterior cingulate cortex (ACC) plays a key role in the development of posttraumatic stress disorder (PTSD). Owing to the region's highly variable patterns, three different studies of PTSD have yielded inconsistent volume reductions. Accordingly, in order to measure the correct borders and volumes, the different patterns of the ACC must be considered separately. We examined 15 victims with chronic symptoms of PTSD, all traumatized at the same accident in 1988, comparing them to 15 matched control subjects. After categorizing the ACC according to single, single segmented, double or double segmented cingulate sulcus (CS), we measured the area with a semi-automated procedure using Brain2 software. Fifty-three percent of our PTSD subjects had single segmented CS compared to 23 % in control subjects and 25 % in the literature. Furthermore, the four patterns showed differences in mean volume over all subjects of up to 13 %. We detected no differences in absolute ACC volumes when differentiating between the patterns or in correlation with brain volumes or clinical parameters. This is the first study to differentiate ACC structure into different patterns in PTSD. We found that one pattern was overrepresented which, in turn, could signal vulnerability to develop PTSD. Because of the remarkable volume differences between patterns, future studies should categorize this highly variable region into different patterns for volumetric measurements. However, future investigations in larger samples should confirm our findings and assess to which extend alterations of ACC patterns may influence the incidence of PTSD.
Archiv f ur Psychiatrie und Nervenkrankheiten 04/2013; · 2.75 Impact Factor
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ABSTRACT: BACKGROUND: Schizophrenia has recently been described as a disorder of impaired plasticity and dysconnectivity. Several lines of evidence suggest that alterations in glutamatergic neurotransmission underlie different symptom domains of schizophrenia. Little is known about the impact of genetic liability on cortical plasticity and connectivity in schizophrenia. OBJECTIVE: To compare N-methyl-d-aspartate receptor (NMDAR)-dependent cortical plasticity and connectivity in schizophrenia patients and unaffected first-degree relatives to that in healthy subjects. METHODS: Cortical plasticity can be induced in the motor cortex with cathodal transcranial direct current stimulation (tDCS). Animal and human research indicates that this long-term depression-like plasticity (LTD-like) is NMDAR dependent, and that these plasticity shifts can last for several hours. tDCS-induced plasticity was assessed by measuring motor-evoked potentials (MEPs) generated by applying transcranial magnetic stimulation (TMS) to both hemispheres in healthy controls, chronically ill schizophrenia patients and unaffected first-degree relatives. RESULTS: Compared to healthy controls, both first-degree relatives and schizophrenia patients showed abolished motor-cortical LTD-like plasticity of the stimulated hemisphere. On the non-stimulated hemisphere, plasticity was again abolished in schizophrenia patients, whereas first-degree relatives had a reversed plasticity. CONCLUSIONS: Non-psychotic and clinically unaffected first-degree relatives showed an alteration and a reversal of LTD-like cortical plasticity, indicating functional alterations of glutamatergic transmission as a result of a genetic liability for developing schizophrenia. These results provide new evidence for the association between plasticity dysregulation and functional cortical connectivity, and the importance of these networks in the pathophysiology of schizophrenia.
Brain Stimulation 03/2013; · 3.76 Impact Factor
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Archiv f ur Psychiatrie und Nervenkrankheiten 03/2013; · 2.75 Impact Factor
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ABSTRACT: Severe psychiatric disorders such as schizophrenia are related to cognitive and negative symptoms, which often are resistant to current treatment approaches. The glutamatergic system has been implicated in the pathophysiology of schizophrenia and affective disorders. A key component is the dysfunction of the glutamatergic N-methyl-D-aspartate (NMDA) receptor. Substances regulating activation/inhibition of the NMDA receptor have been investigated in schizophrenia and major depression and are promising in therapeutic approaches of negative symptoms, cognition, and mood. In schizophrenia, add-on treatments with glycine, D-serine, D-alanine, D-cycloserine, D-amino acid oxidase inhibitors, glycine transporter-1 (GlyT-1) inhibitors (e.g., sarcosine, bitopertin) and agonists (e.g., LY2140023) or positive allosteric modulator (e.g., ADX71149) of group II metabotropic glutamate receptors (mGluRs) have been studied. In major depression, the NMDA receptor antagonists (e.g., ketamine, AZD6765), GluN2B subtype antagonists (e.g., traxoprodil, MK-0657), and partial agonists (e.g., D-cycloserine, GLYX-13) at the glycine site of the NMDA receptor have been proven to be effective in animal studies and first clinical trials. In addition, clinical studies of mGluR2/3 antagonist BCI-838 (a prodrug of BCI-632 (MGS0039)), mGluR2/3-negative allosteric modulators (NMAs) (e.g., RO499819, RO4432717), and mGluR5 NAMs (e.g., AZD2066, RO4917523) are in progress. Future investigations should include effects on brain structure and activation to elucidate neural mechanisms underlying efficacy of these drugs.
Archiv f ur Psychiatrie und Nervenkrankheiten 03/2013; · 2.75 Impact Factor
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Archiv f ur Psychiatrie und Nervenkrankheiten 01/2013; · 2.75 Impact Factor
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Archiv f ur Psychiatrie und Nervenkrankheiten 01/2013; · 2.75 Impact Factor
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ABSTRACT: Background: First-episode schizophrenia (FE-SZ) and attention deficit hyperactivity disorder (ADHD) are both neuropsychiatric disorders associated with an impaired dopaminergic transmission. Though displaying different clinical phenotypes, a common pathophysiological pathway is discussed controversially. Several studies using transcranial magnetic stimulation (TMS) revealed abnormalities in human motor cortex excitability in both schizophrenia and ADHD patients. Studies on cortical excitability comparing these two diseases directly are lacking. Method: In this study, a total of 94 subjects were analyzed. Twenty-five FE-SZ patients were directly compared with 28 ADHD patients and 41 healthy controls (HC). We investigated cortical excitability (inhibitory and facilitatory networks) with single- and paired-pulse TMS to the left and right motor cortex. Results: Compared to HC, FE-SZ/ADHD patients displayed an impaired cortical inhibition over the left hemisphere. Apart from an enhanced intracortical facilitation, FE-SZ patients did not differ compared to ADHD patients in the main outcome measures. Both patient groups presented a dysfunctional hemispheric pattern of cortical inhibition and facilitation in comparison with HC. Conclusion: The results of this study indicate a pattern of cortical disinhibition and abnormal hemispheric balance of intracortical excitability networks in two different psychiatric diseases. These effects might be associated with an imbalance in GABAergic and dopaminergic transmission and might provide evidence for a common pathophysiological pathway of both diseases.
Neuropsychobiology 01/2013; 67(2):74-83. · 2.67 Impact Factor
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ABSTRACT: These updated guidelines are based on a first edition of the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia published in 2006. For this 2012 revision, all available publications pertaining to the biological treatment of schizophrenia were reviewed systematically to allow for an evidence-based update. These guidelines provide evidence-based practice recommendations that are clinically and scientifically meaningful. They are intended to be used by all physicians diagnosing and treating people suffering from schizophrenia. Based on the first version of these guidelines, a systematic review of the MEDLINE/PUBMED database and the Cochrane Library, in addition to data extraction from national treatment guidelines, has been performed for this update. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into six levels of evidence (A-F) and five levels of recommendation (1-5) ( Bandelow et al. 2008a ,b, World J Biol Psychiatry 9:242, see Table 1 ). This second part of the updated guidelines covers long-term treatment as well as the management of relevant side effects. These guidelines are primarily concerned with the biological treatment (including antipsychotic medication and other pharmacological treatment options) of adults suffering from schizophrenia.
The World Journal of Biological Psychiatry 12/2012; · 2.38 Impact Factor
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ABSTRACT: Via influencing brain plasticity, aerobic exercise could contribute to the treatment of schizophrenia patients. As previously shown, physical exercise increases hippocampus volume and improves short-term memory. We now investigated gray matter density and brain surface expansion in this sample using MRI-based cortical pattern matching methods. Comparing schizophrenia patients to healthy controls before and after 3 months of aerobic exercise training (cycling) plus patients playing table football yielded gray matter density increases in the right frontal and occipital cortex merely in healthy controls. However, respective exercise effects might be attenuated in chronic schizophrenia, which should be verified in a larger sample.
Archiv f ur Psychiatrie und Nervenkrankheiten 11/2012; · 2.75 Impact Factor
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Archiv f ur Psychiatrie und Nervenkrankheiten 10/2012; · 2.75 Impact Factor
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Archiv f ur Psychiatrie und Nervenkrankheiten 10/2012; · 2.75 Impact Factor
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Birgit Guse, Peter Falkai,
Oliver Gruber,
Heather Whalley,
Lydia Gibson,
Alkomiet Hasan,
Katrin Obst,
Peter Dechent,
Andrew McIntosh,
Boris Suchan,
Thomas Wobrock
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ABSTRACT: In schizophrenia patients negative symptoms and cognitive impairment often persist despite treatment with second generation antipsychotics leading to reduced quality of life and psychosocial functioning. One core cognitive deficit is impaired working memory (WM) suggesting malfunctioning of the dorsolateral prefrontal cortex. High frequency repetitive transcranial magnetic stimulation (rTMS) has been used to transiently facilitate or consolidate neuronal processes. Pilot studies using rTMS have demonstrated improvement of psychopathology in other psychiatric disorders, but a systematic investigation of working memory effects outlasting the stimulation procedure has not been performed so far. The aim of our study was to explore the effect of a 3-week high frequency active or sham 10Hz rTMS on cognition, specifically on working memory, in schizophrenia patients (n=25) in addition to antipsychotic therapy and in healthy controls (n=22). We used functional magnetic resonance imaging (fMRI) to compare activation patterns during verbal WM (letter 2-back task) before and after 3-weeks treatment with rTMS. Additionally, other cognitive tasks were conducted. 10Hz rTMS was applied over the left posterior middle frontal gyrus (EEG electrode location F3) with an intensity of 110% of the individual resting motor threshold (RMT) over a total of 15 sessions. Participants recruited the common fronto- parietal and subcortical WM network. Multiple regression analyses revealed no significant activation differences over time in any contrast or sample. According to the ANOVAs for repeated measures performance remained without alterations in all groups. This is the first fMRI study that has systematically investigated this topic within a randomized, placebo-controlled, double-blind design, contrasting the effects in schizophrenia patients and healthy controls.
Behavioural brain research 09/2012; 237C:300-307. · 3.22 Impact Factor
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Archiv f ur Psychiatrie und Nervenkrankheiten 09/2012; 262(7):545-6. · 2.75 Impact Factor
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Athanasios Zovoilis,
Hope Y Agbemenyah,
Roberto C Agis-Balboa,
Roman M Stilling,
Dieter Edbauer,
Pooja Rao,
Laurent Farinelli,
Ivana Delalle,
Andrea Schmitt, Peter Falkai,
Sanaz Bahari-Javan,
Susanne Burkhardt,
Farahnaz Sananbenesi,
Andre Fischer
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Athanasios Zovoilis,
Hope Y Agbemenyah,
Roberto C Agis-Balboa,
Roman M Stilling,
Dieter Edbauer,
Pooja Rao,
Laurent Farinelli,
Ivana Delalle,
Andrea Schmitt, Peter Falkai,
Sanaz Bahari-Javan,
Susanne Burkhardt,
Farahnaz Sananbenesi,
Andre Fischer
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Archiv f ur Psychiatrie und Nervenkrankheiten 08/2012; 262(7):547-8. · 2.75 Impact Factor
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ABSTRACT: Substance abuse is the most prevalent comorbid psychiatric condition associated with schizophrenia, and cannabis is the illicit drug most often abused. Apart from worsening the course of schizophrenia, frequent cannabis use especially at an early age seems to be an important risk factor for developing schizophrenia. Although a large body of neuroimaging studies gives evidence for structural alterations in many different brain regions in schizophrenia patients, there is still limited knowledge of the impact of cannabis abuse on brain structure in schizophrenia. We performed a systematic review including structural magnetic resonance imaging studies comparing high-risk and schizophrenia patients with and without cannabis abuse and found inconclusive results. While there is some evidence that chronic cannabis abuse could alter brain morphology in schizophrenia in patients continuing their cannabis consumption, there is no convincing evidence that this alteration takes place before the onset of schizophrenia when looking at first-episode patients. There is some weak evidence that cannabis abuse could affect brain structures in high-risk subjects, but replication of these studies is needed.
Archiv f ur Psychiatrie und Nervenkrankheiten 08/2012; · 2.75 Impact Factor
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Pascal F Durrenberger,
Francisca S Fernando,
Roberta Magliozzi,
Samira N Kashefi,
Timothy P Bonnert,
Isidro Ferrer,
Danielle Seilhean,
Brahim Nait-Oumesmar,
Andrea Schmitt,
Peter J Gebicke-Haerter, Peter Falkai,
Edna Grünblatt,
Miklos Palkovits,
Piero Parchi,
Sabina Capellari,
Thomas Arzberger,
Hans Kretzschmar,
Federico Roncaroli,
David T Dexter,
Richard Reynolds
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ABSTRACT: The use of an appropriate reference gene to ensure accurate normalisation is crucial for the correct quantification of gene expression using qPCR assays and RNA arrays. The main criterion for a gene to qualify as a reference gene is a stable expression across various cell types and experimental settings. Several reference genes are commonly in use but more and more evidence reveals variations in their expression due to the presence of on-going neuropathological disease processes, raising doubts concerning their use. We conducted an analysis of genome-wide changes of gene expression in the human central nervous system (CNS) covering several neurological disorders and regions, including the spinal cord, and were able to identify a number of novel stable reference genes. We tested the stability of expression of eight novel (ATP5E, AARS, GAPVD1, CSNK2B, XPNPEP1, OSBP, NAT5 and DCTN2) and four more commonly used (BECN1, GAPDH, QARS and TUBB) reference genes in a smaller cohort using RT-qPCR. The most stable genes out of the 12 reference genes were tested as normaliser to validate increased levels of a target gene in CNS disease. We found that in human post-mortem tissue the novel reference genes, XPNPEP1 and AARS, were efficient in replicating microarray target gene expression levels and that XPNPEP1 was more efficient as a normaliser than BECN1, which has been shown to change in expression as a consequence of neuronal cell loss. We provide herein one more suitable novel reference gene, XPNPEP1, with no current neuroinflammatory or neurodegenerative associations that can be used for gene quantitative gene expression studies with human CNS post-mortem tissue and also suggest a list of potential other candidates. These data also emphasise the importance of organ/tissue-specific stably expressed genes as reference genes for RNA studies.
Acta Neuropathologica 08/2012; · 9.32 Impact Factor
