Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia

Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia


J Psychiatry Neurosci 2010;35(2):95-104

Bjørn H. Ebdrup, MD, PhD; Birte Glenthøj, MD, DMSc; Hans Rasmussen, PhD; Bodil Aggernaes, MD, PhD; Annika R. Langkilde, MD, PhD; Olaf B. Paulson, MD, DMSc; Henrik Lublin, MD, DMSc; Arnold Skimminge, MSc; William Baaré, PhD

Ebdrup, Glenthøj, Rasmussen, Aggernaes, Lublin — Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Psychiatric Center Glostrup, Copenhagen University Hospital, Glostrup; Ebdrup, Langkilde, Paulson, Skimminge, Baaré — Danish Research Centre for Magnetic Resonance, MR-Department, Copenhagen University Hospital Hvidovre, Hvidovre; Paulson, Baaré — Center for Integrated Molecular Brain Imaging and Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark


Background: Enlarged ventricles and reduced hippocampal volume are consistently found in patients with first-episode schizophrenia. Studies investigating brain structure in antipsychotic-naive patients have generally focused on the striatum. In this study, we examined whether ventricular enlargement and hippocampal and caudate volume reductions are morphological traits of antipsychotic-naive first-episode schizophrenia.

Methods: We obtained high-resolution 3-dimensional T1-weighted magnetic resonance imaging scans for 38 antipsychotic-naive first-episode schizophrenia patients and 43 matched healthy controls by use of a 3-T scanner. We warped the brain images to each other by use of a high-dimensional intersubject registration algorithm. We performed voxel-wise group comparisons with permutation tests. We performed small volume correction for the hippocampus, caudate and ventricles by use of a false discovery rate correction (p < 0.05) to control for multiple comparisons. We derived and analyzed estimates of brain structure volumes. We grouped patients as those with (n = 9) or without (n = 29) any lifetime substance abuse to examine the possible effects of substance abuse. Results: We found that hippocampal and caudate volumes were decreased in patients with first-episode schizophrenia. We found no ventricular enlargement, differences in global volume or significant associations between tissue volume and duration of untreated illness or psychopathology. The hippocampal volume reductions appeared to be influenced by a history of substance abuse. Exploratory analyses indicated reduced volume of the nucleus accumbens in patients with first-episode schizophrenia.

Limitations: This study was not a priori designed to test for differences between schizophrenia patients with or without lifetime substance abuse, and this subgroup was small.

Conclusion: Reductions in hippocampal and caudate volume may constitute morphological traits in antipsychotic-naive first-episode schizophrenia patients. However, the clinical implications of these findings are unclear. Moreover, past substance abuse may accentuate hippocampal volume reduction. Magnetic resonance imaging studies addressing the potential effects of substance abuse in antipsychotic-naive first-episode schizophrenia patients are warranted.

Trial Registration Clinicaltrials.gov NCT00207064, http://clinicaltrials.gov/ct2/show/NCT00207064

Acknowledgments: This study was sponsored by The Danish Medical Research Council, The Copenhagen Hospital Cooperation, The Lundbeck Foundation, Gerda and Aage Haensch’s Foundation, Slagtermester Max Worzner og hustru Inger Worzner’s Foundation and The Danish Psychiatric Association. An unrestricted grant was received from AstraZeneca A/S, Denmark.

Competing interests: None declared.

Contributors: Drs. Ebdrup, Glenthøj, Paulson and Baaré designed the study and wrote the article. Drs. Ebdrup, Glenthøj, Rasmussen, Aggernaes and Baaré acquired the data, which Drs. Ebdrup, Glenthøj, Rasmussen, Langkilde, Lublin, Skimminge and Baaré analyzed. All authors reviewed the article and approved its publication.

DOI: 10.1503/jpn.090049

Correspondence to: Dr. B.H. Ebdrup, Center for Neuropsychiatric Schizophrenia Research, Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Psychiatric Center Glostrup, University Hospital Glostrup, DK-2600 Glostrup, Denmark; fax 45 4323 4653; bebdrup@cnsr.dk