title: Effects of minocycline add-on treatment on brain morphometry and cerebral perfusion in recent-onset schizophrenia.
abstract: Increasing evidence suggests that the tetracycline antibiotic minocycline has neuroprotective effects and is a potential treatment for schizophrenia. However, the mechanisms of action of minocycline in the CNS remain elusive. The aim of this study was to investigate the effects of minocycline on brain morphology and cerebral perfusion in patients with recent-onset schizophrenia after 12months of a randomized double-blind, placebo-controlled clinical trial of minocycline add-on treatment. This study included 24 outpatients with recent-onset schizophrenia randomized for 12months of adjuvant treatment with minocycline (200mg/d) or placebo. MRI (1.5T) and [(99m)Tc]-ECD SPECT brain scans were performed at the end of the 12-month of trial. Between-condition comparisons of SPECT and MRI brain images were performed using statistical parametric mapping and analyzed by voxel-based morphometry (VBM). Minocycline adjuvant treatment significantly reduced positive and negative symptoms when compared with placebo. The VBM analysis of MRI scans showed that the patients in the placebo group had significant lower gray matter volumes in the midposterior cingulate cortex and in the precentral gyrus in comparison with the patients in the minocycline group. In addition, a decreased ECD uptake in the minocycline condition was observed in fronto-temporal areas. These results suggest that minocycline may protect against gray matter loss and modulate fronto-temporal areas involved in the pathophysiology of schizophrenia. Furthermore, minocycline add-on treatment may be a potential treatment in the early stages of schizophrenia and may ameliorate clinical deterioration and brain alterations observed in this period.
authors.affiliation: Department of Neuroscience and Behavior, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, Brazil; National Science and Technology Institute for Translational Medicine (INCT-TM), Brazil. Electronic address: crischaves01@yahoo.com.br.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Chaves
authors.affiliation: Department of Neuroscience and Behavior, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, Brazil; National Science and Technology Institute for Translational Medicine (INCT-TM), Brazil.
authors.forename: Cristiane R
authors.initials: CR
authors.lastname: Marque
authors.affiliation: Department of Neuroscience and Behavior, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, Brazil; National Science and Technology Institute for Translational Medicine (INCT-TM), Brazil; Department of Clinical Medicine, Federal University of Rio Grande do Norte, Brazil.
authors.forename: João P
authors.initials: JP
authors.lastname: Maia-de-Oliveira
authors.affiliation: Department of Neuroscience and Behavior, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, Brazil; Department of Internal Medicine, Division of Nuclear Medicine, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Lauro
authors.initials: L
authors.lastname: Wichert-Ana
authors.affiliation: Department of Neuroscience and Behavior, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, Brazil; National Science and Technology Institute for Translational Medicine (INCT-TM), Brazil.
authors.forename: Thiago B
authors.initials: TB
authors.lastname: Ferrari
authors.affiliation: Department of Neuroscience and Behavior, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, Brazil; Department of Internal Medicine, Division of Radiology, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Santos
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Araújo
authors.affiliation: Department of Neuroscience and Behavior, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, Brazil; National Science and Technology Institute for Translational Medicine (INCT-TM), Brazil.
authors.forename: João P
authors.initials: JP
authors.lastname: Machado-de-Sousa
authors.affiliation: Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Federal University of São Paulo, Brazil.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Bressan
authors.affiliation: Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Brazil.
authors.forename: Helio
authors.initials: H
authors.lastname: Elkis
authors.affiliation: Department of Neuroscience and Behavior, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, Brazil; National Science and Technology Institute for Translational Medicine (INCT-TM), Brazil.
authors.forename: José A
authors.initials: JA
authors.lastname: Crippa
authors.affiliation: Department of Neuroscience and Behavior, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, Brazil; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Guimarães
authors.affiliation: Department of Neuroscience and Behavior, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, Brazil; National Science and Technology Institute for Translational Medicine (INCT-TM), Brazil.
authors.forename: Antônio W
authors.initials: AW
authors.lastname: Zuardi
authors.affiliation: National Science and Technology Institute for Translational Medicine (INCT-TM), Brazil; Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Canada.
authors.forename: Glen B
authors.initials: GB
authors.lastname: Baker
authors.affiliation: National Science and Technology Institute for Translational Medicine (INCT-TM), Brazil; Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Canada.
authors.forename: Serdar M
authors.initials: SM
authors.lastname: Dursun
authors.affiliation: Department of Neuroscience and Behavior, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, Brazil; National Science and Technology Institute for Translational Medicine (INCT-TM), Brazil.
authors.forename: Jaime E C
authors.initials: JE
authors.lastname: Hallak
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008911:Minocycline / Q000627:therapeutic use*; D009929:Organ Size; D015609:Organotechnetium Compounds; D011569:Psychiatric Status Rating Scales; D019275:Radiopharmaceuticals; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D012815:Signal Processing, Computer-Assisted; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D008911:Minocycline; C059659:technetium Tc 99m bicisate; D003545:Cysteine
keywords: MRI; Minocycline; Neuroimaging; SPECT; Schizophrenia; VBM