J Psychiatry Neurosci 2010;35(1):33-40
Henning Witthaus, MD; Ute Mendes, MD; Martin Brüne, MD, PhD; Seza Özgürdal, MSc; Georg Bohner, MD; Yehonala Gudlowski, Msc; Peter Kalus, MD; Nancy Andreasen, MD, PhD; Andreas Heinz, MD, PhD; Randolf Klingebiel, MD, PhD; Georg Juckel, MD, PhD
Witthaus, Brüne, Özgürdal, Juckel — Early Recognition and Therapy Centre for Beginning Psychoses Bochum, Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, Ruhr-University of Bochum; Mendes, Gudlowski, Kalus, Heinz — Early Recognition and Therapy Centre for Beginning Psychoses Berlin, Department of Psychiatry and Psychotherapy, Charité Campus Mitte; Bohner, Klingebiel — Department of Neuroradiology, Charité Campus Mitte, Berlin, Germany; Andreasen — Iowa Mental Health Clinical Research Center, University of Iowa, Iowa City, Iowa
Background: Accumulating evidence from postmortem and magnetic resonance imaging (MRI) studies suggests that abnormalities of medial temporal lobe structures are critically involved in the pathogenesis of schizophrenia. It is still unclear, however, whether certain abnormalities are already present in individuals at ultra high-risk (UHR) for transition into psychosis. Recent studies involving patients at UHR showed contradictory results for hippocampal volume, and only 1 study reported that amygdalar volume was unchanged between healthy patients and those at UHR. Furthermore, no subregions of the hippocampus have been investigated in people at UHR.
Methods: We recruited 29 UHR patients, 23 first-episode patients and 29 age- and sex-matched healthy controls. We measured hippocampal and amygdalar volumes from MRI scans by use of BRAINS2 to manually trace the regions of interest. The hippocampi were divided in 2 regions: head and corpus/tail.
Results: Patients at UHR had significantly smaller volumes of the hippocampus corpus and tail bilaterally, but not of the head, compared with healthy controls. Group differences for the right hippocampus corpus and tail volume remained significant after we controlled for whole brain volume and other covariates. We found that UHR patients who later developed psychosis had smaller right hippocampus corpus and tail volumes than did those who did not develop psychosis. First-episode patients had significantly smaller left amygdalar volumes than did healthy individuals or those at UHR.
Limitations: Our study had a small sample size, and we were unable to control for the effects of medication. Conclusion: Our findings suggest that parts of the hippocampal–amygdalar complex are involved in the pathogenesis of schizophrenia. Reduction of hippocampus corpus and tail volumes may be indicative of the prodromal phase of schizophrenia and represent risk factors for transition into psychosis. Further investigations are needed to determine whether structural changes of the left amygdala play a role during transition from the prodromal phase to the first manifest episode of schizophrenia.
Acknowledgments: This study was supported in part by an unrestricted grant from the Charities Aid Foundation and was, in part, associated with the framework of the European Prediction of Psychosis Study (EPOS, QLRT-2000-01081, European Commission 5th Program).
Competing interests: Andreas Heinz has received research funding from the German Research Foundation and the Bernstein Centre for Computational Neuroscience Berlin (German Federal Ministry of Education and Research), Eli Lilly & Company, Janssen-Cilag and Bristol-Myers Squibb. Dr. Heinz has received speaker honoraria from Janssen-Cilag, Johnson & Johnson, Eli Lilly, Pfizer, Bristol-Myers Squibb, AstraZeneca and Servier. Georg Juckel has received consultancy fees from Janssen-Cilag, AstraZeneca and Eli Lilly. He has received speaker fees and/or educational grants from Janssen-Cilag, AstraZeneca, Eli Lilly, Wyeth and Pfizer.
None declared for Henning Witthaus, Ute Mendes, Martin Brune, Seza Özgürdal, George Bohner, Yehonala Gudlowski, Peter Kalusand Randolf Klingebiel.
Contributors: Drs. Witthaus, Mendes and Juckel contributed to the conception and design of the study and the acquisition, analysis and interpretation of data. Dr. Heinz contributed to the conception and design of the study and the acquisition of data. Dr. Klaus contributed to the conception and design of the article and the analysis and interpretation of data. Drs. Özgürdal, Klingebiel and Bohner contributed to the acquisition of the data. Dr. Juckel wrote the article, which he revised along with the other authors. All authors approved the final version submitted for publication. All authors had full access to all of the data in the study and all analyses
Submitted Feb. 2, 2009; Revised Jul. 12, Sep. 1, 2009; Accepted Sep. 7, 2009.
Correspondence to: Dr. G. Juckel, Department of Psychiatry, Ruhr-University of Bochum, LWL University Hospital, Alexandrinenstr. 1, 44791 Bochum, Germany; fax 49 0234 5077 204;