Browsing by Author "Winterer, Georg"

Cognitive impairments are one of the main contributors to disability and poor long-term outcome in schizophrenia. Proof-of-concept trials indicate that repetitive transcranial magnetic stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (DLPFC) has the potential to improve cognitive functioning. We analyzed the effects of 10-Hz rTMS to the left DLPFC on cognitive deficits in schizophrenia in a large-scale and multicenter, sham-controlled study. A total of 156 schizophrenia patients with predominant negative symptoms were randomly assigned to a 3-week intervention (10-Hz rTMS, 15 sessions, 1000 stimuli per session) with either active or sham rTMS. The Rey Auditory Verbal Learning Test, Trail Making Test A and B, Wisconsin Card Sorting Test, Digit Span Test, and the Regensburg Word Fluency Test were administered before intervention and at day 21, 45, and 105 follow-up. From the test results, a neuropsychological composite score was computed. Both groups showed no differences in any of the outcome variables before and after intervention. Both groups improved markedly over time, but effect sizes indicate a numeric, but nonsignificant superiority of active rTMS in certain cognitive tests. Active 10-Hz rTMS applied to the left DLPFC for 3 weeks was not superior to sham rTMS in the improvement of various cognitive domains in schizophrenia patients with predominant negative symptoms. This is in contrast to previous preliminary proof-of-concept trials, but highlights the need for more multicenter randomized controlled trials in the field of non-invasive brain stimulation.

We conducted a randomized, sham-controlled repetitive transcranial magnetic stimulation (rTMS) study in chronic schizophrenia in-patients (n = 35) to evaluate the therapeutic efficacy of 10 Hz stimulation. Patients, who were on stable antipsychotic treatment, were randomly assigned to the active or sham condition. In the active rTMS group, ten sessions with a total of 10,000 stimuli were applied over the left dorsolateral prefrontal cortex at 110% of motor threshold. The sham group received corresponding sham stimulation. Clinical improvement was measured by the Clinical Global Impression scale (primary outcome measure), the Global Assessment of Functioning Scale (GAF) and the Positive and Negative Symptom Scale (PANSS; secondary outcome measures). Between-group comparisons revealed no significant differences in clinical outcome variables. Only a subgroup of patients with pronounced negative symptoms developed some clinical improvement as indicated by significant changes in the GAF-scale. Besides there is some evidence for a more favourable clinical outcome within this subgroup after rTMS in the CGI-S and PANSS negative scale, too. In line with earlier investigations, our results suggest a moderate potentially clinically relevant treatment effect of prefrontal 10 Hz rTMS stimulation in chronic patients. However, in our study this beneficial effect was restricted to subjects with pronounced negative symptoms.

Repetitive transcranial magnetic stimulation (rTMS) applied to the left frontal lobe is discussed to be a promising add-on treatment for negative symptoms in schizophrenia. The Positive and Negative Syndrome Scale (PANSS) has been used as outcome parameter in several previous rTMS trials, but studies focusing on PANSS factor analyses are lacking. For this purpose, we used the available PANSS data of the 'rTMS for the Treatment of Negative Symptoms in Schizophrenia' (RESIS) trial to calculate different literature-based PANSS factors and to re-evaluate the impact of rTMS on negative symptoms in this trial. In an exploratory re-analysis of published data from the RESIS study (Wobrock et al. 2015), we tested the impact of rTMS applied to the left dorsolateral prefrontal cortex on two PANSS factors for negative symptoms in psychotic disorders as well as on a PANSS five-factor consensus model intending to show that active rTMS treatment improves PANSS negative symptom subscores. In accordance to the original analysis, all PANSS factors showed an improvement over time in the active and, to a considerable extent, also in the sham rTMS group. However, comparing the data before and directly after the rTMS intervention, the PANSS excitement factor improved in the active rTMS group significantly more than in the sham group, but this finding did not persist if follow-up data were taken into account. These additional analyses extend the previously reported RESIS trial results showing unspecific improvements in the PANSS positive subscale in the active rTMS group. Our PANSS factor-based approach to investigate the impact of prefrontal rTMS on different negative symptom domains confirmed no overall beneficial effect of the active compared to sham rTMS.

Cigarette smoking is a severe health burden being related to a number of chronic diseases. Frequently, smokers report about sleep problems. Sleep disturbance, in turn, has been demonstrated to be involved in the pathophysiology of several disorders related to smoking and may be relevant for the pathophysiology of nicotine dependence. Therefore, determining the frequency of sleep disturbance in otherwise healthy smokers and its association with degree of nicotine dependence is highly relevant. In a population-based case-control study, 1071 smokers and 1243 non-smokers without lifetime Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I disorder were investigated. Sleep quality (SQ) of participants was determined by the Pittsburgh Sleep Quality Index. As possible confounders, age, sex and level of education and income, as well as depressiveness, anxiety, attention deficit hyperactivity, alcohol drinking behaviour and perceived stress, were included into multiple regression analyses. Significantly more smokers than non-smokers (28.1% versus 19.1%; P < 0.0001) demonstrated a disturbed global SQ. After controlling for the confounders, impaired scores in the component scores of sleep latency, sleep duration and global SQ were found significantly more often in smokers than non-smokers. Consistently, higher degrees of nicotine dependence and intensity of smoking were associated with shorter sleep duration. This study demonstrates for the first time an elevated prevalence of sleep disturbance in smokers compared with non-smokers in a population without lifetime history of psychiatric disorders even after controlling for potentially relevant risk factors. It appears likely that smoking is a behaviourally modifiable risk factor for the occurrence of impaired SQ and short sleep duration.

BACKGROUND: Investigators are urgently searching for options to treat negative symptoms in schizophrenia because these symptoms are disabling and do not respond adequately to antipsychotic or psychosocial treatment. Meta-analyses based on small proof-of-principle trials suggest efficacy of repetitive transcranial magnetic stimulation (rTMS) for the treatment of negative symptoms and call for adequately powered multicenter trials. This study evaluated the efficacy of 10-Hz rTMS applied to the left dorsolateral prefrontal cortex for the treatment of predominant negative symptoms in schizophrenia. METHODS: A multicenter randomized, sham-controlled, rater-blinded and patient-blinded trial was conducted from 2007-2011. Investigators randomly assigned 175 patients with schizophrenia with predominant negative symptoms and a high-degree of illness severity into two treatment groups. After a 2-week pretreatment phase, 76 patients were treated with 10-Hz rTMS applied 5 days per week for 3 weeks to the left dorsolateral prefrontal cortex (added to the ongoing treatment), and 81 patients were subjected to sham rTMS applied similarly. RESULTS: There was no statistically significant difference in improvement in negative symptoms between the two groups at day 21 (p = .53, effect size = .09) or subsequently through day 105. Also, symptoms of depression and cognitive function showed no differences in change between groups. There was a small, but statistically significant, improvement in positive symptoms in the active rTMS group (p = .047, effect size = .30), limited to day 21. CONCLUSIONS: Application of active 10-Hz rTMS to the left dorsolateral prefrontal cortex was well tolerated but was not superior compared with sham rTMS in improving negative symptoms; this is in contrast to findings from three meta-analyses.

Metabolic Syndrome (MetS) is one of the most common factors underlying the high rate of mortality observed in patients with schizophrenia. Recent research on this topic revealed that many of the patients studied were, in fact, in a medicated state. As such, it is unclear whether MetS is causally associated with the disorder itself or the medication used to treat it. In this study, patients with a clinically high risk of expressing first episode psychosis (CHR) were examined regarding the prevalence of MetS. N = 144 unmedicated and antipsychotic-naive CHR patients, aged between 18 and 42 years and suffering from unmanifested prodromal symptoms, were compared with a cohort of N = 3995 individuals from the "German Metabolic and Cardiovascular Risk Study" (GEMCAS). A slightly higher prevalence of individual MetS criteria was observed in the CHR group compared to the GEMCAS sample; specifically, the following were noted: a higher blood pressure (35.0% vs. 28.0%), increased waist circumference (17.6% vs. 15.1%), and increased fasting blood glucose (9.4% vs. 4.0%) in CHR patients. Additionally, the rate of reduced HDL cholesterol concentrations was lower in the control group (20.2% vs. 13.3%). (C) 2016 Elsevier B.V. All rights reserved.

Current meta-analysis revealed small, but significant effects of repetitive transcranial magnetic stimulation (rTMS) on negative symptoms in patients with schizophrenia. There is a need for further controlled, multicenter trials to assess the clinical efficacy of rTMS on negative symptoms in schizophrenia in a larger sample of patients. The objective of this multicenter, randomized, sham-controlled, rater- and patient-blind clinical trial is to investigate the efficacy of 3-week 10-Hz high frequency rTMS add on to antipsychotic therapy, 15 sessions per 3 weeks, 1,000 stimuli per session, stimulation intensity 110% of the individual motor threshold) of the left dorsolateral prefrontal cortex for treating negative symptoms in schizophrenia, and to evaluate the effect during a 12 weeks of follow-up. The primary efficacy endpoint is a reduction of negative symptoms as assessed by the negative sum score of the positive and negative symptom score (PANSS). A sample size of 63 in each group will have 80% power to detect an effect size of 0.50. Data analysis will be based on the intention to treat population. The study will be conducted at three university hospitals in Germany. This study will provide information about the efficacy of rTMS in the treatment of negative symptoms. In addition to psychopathology, other outcome measures such as neurocognition, social functioning, quality of life and neurobiological parameters will be assessed to investigate basic mechanisms of rTMS in schizophrenia. Main limitations of the trial are the potential influence of antipsychotic dosage changes and the difficulty to ensure adequate blinding.

Impaired neural plasticity may be a core pathophysiological process underlying the symptomatology of schizophrenia. Plasticity-enhancing interventions, including repetitive transcranial magnetic stimulation (rTMS), may improve difficult-to-treat symptoms; however, efficacy in large clinical trials appears limited. The high variability of rTMS-related treatment response may be related to a comparably large variation in the ability to generate plastic neural changes. The aim of the present study was to determine whether negative symptom improvement in schizophrenia patients receiving rTMS to the left dorsolateral prefrontal cortex (DLPFC) was related to rTMS-related brain volume changes. A total of 73 schizophrenia patients with predominant negative symptoms were randomized to an active (n = 34) or sham (n = 39) 10-Hz rTMS intervention applied 5 days per week for 3 weeks to the left DLPFC. Local brain volume changes measured by deformation-based morphometry were correlated with changes in negative symptom severity using a repeated-measures analysis of covariance design. Volume gains in the left hippocampal, parahippocampal and precuneal cortices predicted negative symptom improvement in the active rTMS group (all r <= - 0.441, all P <= 0.009), but not the sham rTMS group (all r <= 0.211, all P >= 0.198). Further analyses comparing negative symptom responders (>= 20% improvement) and non-responders supported the primary analysis, again only in the active rTMS group (F-(9,F- 207) = 2.72, P = 0.005, partial n(2) = 0.106). Heterogeneity in clinical response of negative symptoms in schizophrenia to prefrontal high-frequency rTMS may be related to variability in capacity for structural plasticity, particularly in the left hippocampal region and the precuneus.