title: Cognitive Effects of High-Frequency rTMS in Schizophrenia Patients With Predominant Negative Symptoms: Results From a Multicenter Randomized Sham-Controlled Trial.
abstract: 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 noninvasive brain stimulation.
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany; These authors contributed equally to the article. alkomiet.hasan@med.uni-muenchen.de.
authors.forename: Alkomiet
authors.initials: A
authors.lastname: Hasan
authors.affiliation: Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, Göttingen, Germany; These authors contributed equally to the article.
authors.forename: Birgit
authors.initials: B
authors.lastname: Guse
authors.affiliation: Department of Psychiatry and Psychotherapy, Heinrich-Heine University, Düsseldorf, Germany;
authors.forename: Joachim
authors.initials: J
authors.lastname: Cordes
authors.affiliation: Department of Psychiatry and Psychotherapy, Heinrich-Heine University, Düsseldorf, Germany;
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wölwer
authors.affiliation: The Charité - Universitätsmedizin Berlin, Berlin, Germany;
authors.forename: Georg
authors.initials: G
authors.lastname: Winterer
authors.affiliation: Department of Psychiatry and Psychotherapy, Heinrich-Heine University, Düsseldorf, Germany;
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Gaebel
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany;
authors.forename: Berthold
authors.initials: B
authors.lastname: Langguth
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany; Department of Psychiatry, Psychosomatics and Psychotherapy, kbo-Lech-Mangfall-Klinik, Agatharied, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Landgrebe
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany;
authors.forename: Peter
authors.initials: P
authors.lastname: Eichhammer
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany;
authors.forename: Elmar
authors.initials: E
authors.lastname: Frank
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, Sozialstiftung Bamberg, Bamberg, Germany;
authors.forename: Göran
authors.initials: G
authors.lastname: Hajak
authors.affiliation: Coordination Centre for Clinical Trials, Heinrich-Heine University, Düsseldorf, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Ohmann
authors.affiliation: Coordination Centre for Clinical Trials, Heinrich-Heine University, Düsseldorf, Germany;
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Verde
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Institute of Central Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany;
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Institut für anwendungsorientierte Forschung und klinische Studien GmbH, Göttingen, Germany;
authors.forename: Raees
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: Institute of Mental Health, The University of British Columbia, Vancouver, British Columbia, Canada;
authors.forename: William G
authors.initials: WG
authors.lastname: Honer
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany;
authors.forename: Berend
authors.initials: B
authors.lastname: Malchow
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany;
authors.forename: Susanne
authors.initials: S
authors.lastname: Karch
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider-Axmann
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany;
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
authors.affiliation: Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, Göttingen, Germany; County Hospitals Darmstadt-Dieburg, Groß-Umstadt, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wobrock
mesh_terms: D000328:Adult; D060825:Cognitive Dysfunction / Q000209:etiology / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010919:Placebos; D012559:Schizophrenia / Q000150:complications / Q000628:therapy*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D010919:Placebos
keywords: brain plasticity; cognition; negative symptoms; repetitive magnetic stimulation; schizophrenia