Hippocampal volume in first episode and recurrent depression Klaus-Thomas Kronmüller a, ⁎, Johannes Schröder b , Sebastian Köhler a , Bianca Götz a , Daniela Victor a , Jörg Unger a , Frederic Giesel c , Vincent Magnotta d , Christoph Mundt a , Marco Essig c , Johannes Pantel e a Department of Psychiatry, University of Heidelberg, Germany b Section of Geriatric Psychiatry, University of Heidelberg, Germany c Department of Radiology, German Cancer Research Center, Heidelberg, Germany d Mental Health Clinical Research Center, Department of Psychiatry, University of Iowa, Iowa City, IA, USA e Department of Psychiatry and Psychotherapy, University of Frankfurt/Main, Germany abstract article info Article history: Received 9 March 2007 Received in revised form 17 December 2007 Accepted 5 August 2008 Keywords: Affective disorders Structural brain imaging Gender effects Abnormalities in limbic–thalamic–cortical networks are hypothesized to modulate human mood states. In the present study differences in hippocampal volumes of patients with a first episode of depression, recurrent major depression and healthy control subjects were examined with high-resolution magnetic resonance imaging (MRI). Male patients with a first episode of major depression had a significantly smaller left hippocampal volume than male control subjects. Also, these patients had a significant left–right asymmetry in hippocampal volume. Female patients showed no significant alterations in hippocampal volumes. The results support the hypothesis that the hippocampus plays an important role in the pathophysiology of the early phase of major depression, especially for male patients. Implications for the neurodevelopmental and the neurodegenerative model of hippocampal change are discussed. © 2008 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Increasing evidence has shown structural cerebral abnormalities in limbic–thalamic–cortical networks in patients with unipolar depression (Soares and Mann, 1997; Campbell and MacQueen, 2003, 2006). A core area in these networks is the hippocampus, which is involved in memory and emotional regulation deficits that often accompany depression. Several structural imaging studies have found abnormalities in hippo- campal volumes in patients with depression. Some of these studies found a smaller volume unilaterally, others found a bilaterally smaller one, and still others could not find any differences compared with healthy controls (Videbech and Ravnkilde, 2004; Campbell et al., 2004; Campbell and MacQueen, 2006). In recent studies a smaller hippocampal volume has been found only in subsamples of depressed patients. It has been presumed that the inconsistencies in results cannot solely be ascribed to the heterogeneity of MRI methods but also to the sampling, which was inconsistent concerning the proportion of first episode and recurrently depressed patients as well as the gender ratio (Videbech and Ravnkilde, 2004; Campbell et al., 2004). Frodl et al. (2002) compared depressive men and women with healthy controls and found a smaller left hippocampal volume only for men with a first episode of major depression. MacMaster and Kusumakar (2004) found an even more pronounced reduction in left hippocampal volume in male adolescent patients. In contrast, MacQueen et al. (2003) found that patients with multiple episodes in comparison to first episode patients were more likely to have smaller hippocampal volumes. To date, only one study exists, namely that of MacQueen et al. (2003), which systematically compares first episode and recurrently depressed patients, and also considers gender effects. The aim of the present study therefore was to compare the hippocampal formation of male and female patients with a first episode and recurrent depression to that of healthy control subjects. The hypotheses were that depressed patients have a smaller hippocam- pal volume in comparison to healthy control subjects and that patients with multiple episodes have a smaller hippocampal volume in comparison to patients with a first episode of major depression. 2. Methods 2.1. Subjects Fifty-seven inpatients with major depression according to DSM-IV (American Psychiatric Association, 1994) treated in the Department of Psychiatry of the University in Heidelberg were recruited. The diagnoses were made using a structured clinical interview (SCID; Wittchen et al., 1997). The mean age of the 33 female and 24 male patients was 43.54 (S.D. = 12.82, 18–64) at initial assessment. Twenty- seven (47.37%) patients were married. Twenty-two (38.60%) had a high and 35 (61.40%) a low level of school education. Twenty-six (45.61%) patients had a first episode of major depression. The mean score in the 17-item Hamilton Depression Rating Scale (HDRS; Hamilton, 1960) was 22.74 (S.D.=6.58) at admission to treatment. Psychiatry Research: Neuroimaging 174 (2009) 62–66 ⁎ Corresponding author. Department of Psychiatry, University of Heidelberg, Voßstraße 4, D-69115 Heidelberg, Germany. Tel.: +49 6221 5632747; fax: +49 6221 565477. E-mail address: klaus_kronmueller@med.uni-heidelberg.de (K.-T. Kronmüller). 0925-4927/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pscychresns.2008.08.001 Contents lists available at ScienceDirect Psychiatry Research: Neuroimaging journal homepage: www.elsevier.com/locate/psychresns