Differential brain glucose metabolic patterns in antipsychotic-naive first-episode schizophrenia with and without auditory verbal hallucinations

Differential brain glucose metabolic patterns in antipsychotic-naive first-episode schizophrenia with and without auditory verbal hallucinations


J Psychiatry Neurosci 2011;36(5):312-21

Guillermo Horga, MD; Eduard Parellada, MD, PhD; Francisco Lomeña, MD, PhD; Emilio Fernández-Egea, MD, PhD; Anna Mané, MD; Mireia Font, PhD; Carles Falcón, PhD; Anna B. Konova, MA; Javier Pavia, PhD; Domènec Ros, PhD; Miguel Bernardo, MD, PhD

Horga, Parellada, Fernández-Egea, Mané, Font, Bernardo — Clinic Schizophrenia Program, Psychiatry Department, Hospital Clinic of Barcelona, Barcelona, Spain; Horga, Parellada, Ros, Bernardo — University of Barcelona, Barcelona, Spain; Parellada, Lomeña, Fernández-Egea, Bernardo — Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain; Parellada, Lomeña, Falcón, Bernardo — Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Lomeña, Pavia — Nuclear Medicine Department, Centre of Diagnostic Imaging, Hospital Clinic of Barcelona, Spain; Lomeña — CETIR Unitat PET Centre, Esplugues de Llobregat, Spain; Fernández-Egea — Department of Psychiatry, University of Cambridge, Cambridge, and the Cambridgeshire and Peterborough NHS Foundation Trust. Huntingdon, UK; Mané — Centre Forum, Barcelona, Spain; Falcón — Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain; Konova — Department of Psychology, Stony Brook University, Stony Brook, NY


Background: Auditory verbal hallucinations (AVHs) are a core symptom of schizophrenia. Previous reports on neural activity patterns associated with AVHs are inconsistent, arguably owing to the lack of an adequate control group (i.e., patients with similar characteristics but without AVHs) and neglect of the potential confounding effects of medication.

Methods: The current study was conducted in a homogeneous group of patients with schizophrenia to assess whether the presence or absence of AVHs was associated with differential regional cerebral glucose metabolic patterns. We investigated differences between patients with commenting AVHs and patients without AVHs among a group of dextral antipsychotic-naive inpatients with acute first-episode schizophrenia examined with [18F]fluoro-deoxyglucose positron emission tomography (FDG-PET) at rest. Univariate and multivariate approaches were used to establish between-group differences.

Results: We included 9 patients with AVHs and 7 patients without AVHs in this study. Patients experiencing AVHs during FDG uptake had significantly higher metabolic rates in the left superior and middle temporal cortices, bilateral superior medial frontal cortex and left caudate nucleus (cluster level p < 0.005, family wise error–corrected, and bootstrap ratio > 3.3, respectively). Additionally, the multivariate method identified hippocampal–parahippocampal, cerebellar and parietal relative hypoactivity during AVHs in both hemispheres (bootstrap ratio < –3.3). Limitations: The FDG-PET imaging technique does not provide information regarding the temporal course of neural activity. The limited sample size may have increased the risk of false-negative findings.

Conclusion: Our results indicate that AVHs in patients with schizophrenia may be mediated by an alteration of neural pathways responsible for normal language function. Our findings also point to the potential role of the dominant caudate nucleus and the parahippocampal gyri in the pathophysiology of AVHs. We discuss the relevance of phenomenology-based grouping in the study of AVHs.

Submitted May 23, 2010; Revised Aug. 11, 2010; Accepted Oct. 15, 2010.

Acknowledgments: This work was supported by the Fundació Marató of TV3 (registered number 012410), Janssen-Cilag; and Ministerio de Ciencia y Tecnología (grant number SAF-2002–04270-C02–02), the Fondo de Investigación Sanitaria (grant numbers G03/185, C03/06), DIUE (Government of Catalonia, Comissionat per Universitats I Recerca del Departament d’Innovació, Universitats I Empresa, grant number 2009SGR1295) and the Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM. The authors thank the Fundación Española de Psiquiatría y Salud Mental for providing funding for research training.

Competing interests: Dr. Horga declares having received grant and travel support from the Alicia Koplowitz Foundation. Dr. Parellada declares having received grant support and lecture fees from Janssen-Cilag and GlaxoSmithKline and grant support from Lilly. Dr. Lomeña declares having received lecture fees from GE Healthcare. Dr. Font declares having received grant support from Maraton TV3 and Janssen-Cilag and travel support from Janssen-Cilag. Dr. Bernardo declares having received grant support from Bristol-Myers Squibb, CIBERSAM, Eli Lilly, FIS-Institute of Health Carlos III, the Government of Catalonia, Janssen-Cilag, Marató TV3, Organon and Pfizer, and declared board membership with and lecture fees from Bristol- Myers Squibb, Eli Lilly, Janssen-Cilag, Mylan and Pfizer. None declared for Drs. Fernández-Egea, Mané, Falcón, Konova, Pavia and Ros.

Contributors: Dr. Horga designed the study, performed the analyses, interpreted the results and drafted the manuscript. Drs. Parellada, Lomeña, Fernández-Egea, Font and Bernardo designed the study protocol. Drs. Konova, Mané and Falcón assisted with data analyses, provided methodological advice and helped editing the manuscript. Drs. Pavia, Ros and Lomeña supervised the imaging protocol and data collection. All authors contributed to, revised and approved the final manuscript.

DOI: 10.1503/jpn.100085

Correspondence to: Dr. G. Horga, Clinic Schizophrenia Program, Psychiatry Department, Clinical Institute of Neurosciences, Hospital Clinic of Barcelona, Villarroel 170, 08036 Barcelona, Spain; guillermo.horga@gmail.com or horgag@childpsych.columbia.edu