title: Imaging the neuroplastic effects of ketamine with VBM and the necessity of placebo control.
abstract: In the last years a plethora of studies have investigated morphological changes induced by behavioural or pharmacological interventions using structural T1-weighted MRI and voxel-based morphometry (VBM). Ketamine is thought to exert its antidepressant action by restoring neuroplasticity. In order to test for acute impact of a single ketamine infusion on grey matter volume we performed a placebo-controlled, double-blind investigation in healthy volunteers using VBM. 28 healthy individuals underwent two MRI sessions within a timeframe of 2 weeks, each consisting of two structural T1-weighted MRIs within a single session, one before and one 45min after infusion of S-ketamine (bolus of 0.11mg/kg, followed by an maintenance infusion of 0.12mg/kg) or placebo (0.9% NaCl infusion) using a crossover design. In the repeated-measures ANOVA with time (post-infusion/pre-infusion) and medication (placebo/ketamine) as factors, no significant effect of interaction and no effect of medication was found (FWE-corrected). Importantly, further post-hoc t-tests revealed a strong "decrease" of grey matter both in the placebo and the ketamine condition over time. This effect was evident mainly in frontal and temporal regions bilaterally with t-values ranging from 4.95 to 5.31 (FWE-corrected at p<0.05 voxel level). The vulnerabilities of VBM have been repeatedly demonstrated, with reports of influence of blood flow, tissue water and direct effects of pharmacological compounds on the MRI signal. Here again, we highlight that the relationship between intervention and VBM results is apparently subject to a number of physiological influences, which are partly unknown. Future studies focusing on the effects of ketamine on grey matter should try to integrate known influential factors such as blood flow into analysis. Furthermore, the results of this study highlight the importance of a carefully performed placebo condition in pharmacological fMRI studies.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Höflich
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Ganger
authors.affiliation: MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Tik
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Hahn
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: G S
authors.initials: GS
authors.lastname: Kranz
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Vanicek
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Spies
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Kraus
authors.affiliation: MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Windischberger
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Kasper
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: D
authors.initials: D
authors.lastname: Winkler
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria. Electronic address: rupert.lanzenberger@meduniwien.ac.at.
authors.forename: R
authors.initials: R
authors.lastname: Lanzenberger
mesh_terms: D000328:Adult; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D066128:Gray Matter / Q000033:anatomy & histology / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007649:Ketamine / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D010919:Placebos; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012107:Research Design; D055815:Young Adult
chemical_list: D000778:Anesthetics, Dissociative; D010919:Placebos; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine
keywords: Brain structure; Ketamine; MRI; Neuroplasticity; VBM