title: Structural brain changes are associated with response of negative symptoms to prefrontal repetitive transcranial magnetic stimulation in patients with schizophrenia.
abstract: 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, 207)=2.72, P=0.005, partial η2=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.
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hasan
authors.affiliation: Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, Göttingen, Germany.|Department of Psychiatry and Psychotherapy, County Hospitals Darmstadt-Dieburg, Groß-Umstadt, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Wobrock
authors.affiliation: Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Guse
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany.
authors.forename: B
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, Agatharied, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Landgrebe
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Eichhammer
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Frank
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Cordes
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Wölwer
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Musso
authors.affiliation: Experimental and Clinical Research Centre, The Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Winterer
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Gaebel
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, Sozialstiftung Bamberg, Bamberg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Hajak
authors.affiliation: European Clinical Research Network, Düsseldorf, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Ohmann
authors.affiliation: Coordination Centre for Clinical Trials, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: P 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: M
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Institut für anwendungsorientierte Forschung und klinische Studien GmbH, Göttingen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Institute of Mental Health, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: W G
authors.initials: WG
authors.lastname: Honer
authors.affiliation: Department of Cognitive Neurology, Georg-August-University Goettingen, Goettingen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Dechent
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Malchow
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: M F U
authors.initials: MFU
authors.lastname: Castro
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Dwyer
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Cabral
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany.
authors.forename: P M
authors.initials: PM
authors.lastname: Kreuzer
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany.
authors.forename: T B
authors.initials: TB
authors.lastname: Poeppl
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Schneider-Axmann
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Falkai
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Koutsouleris
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications / Q000628:therapy*; D050781:Transcranial Magnetic Stimulation / Q000379:methods* / Q000523:psychology; D016896:Treatment Outcome