Brief report
Hippocampal atrophy in first episode depression: A meta-analysis of magnetic resonance imaging studies

https://doi.org/10.1016/j.jad.2011.05.057Get rights and content

Abstract

Background

Reduced hippocampal volume has been consistently observed in major depressive disorder. Hippocampal volume loss is particularly evident in patients with recurrent and chronic depression. However, the reports in first episode depression have been mixed.

Methods

We performed a random effects meta-analysis to establish whether hippocampal atrophy exists from disease onset. We included magnetic resonance imaging studies of hippocampal volume in patients with first episode major depressive disorder and matched healthy controls.

Results

A total of 7 studies met our inclusion and exclusion criteria, representing independent observations in a total sample of 191 patients and 282 healthy controls. The cumulative analysis revealed hippocampal volume loss in patients with first episode depression relative to controls in both the left (standardised mean difference, SMD =  0.41, 95% Confidence Interval: [− 0.78;−0.03], z =  2.14, p = 0.0321) and right (SMD =  0.53[− 0.98;−0.09], z =  2.38, p = 0.0173) hippocampi. The average volume reduction was − 4.0% in the left and − 4.5% in the right hippocampus.

Conclusions

Hippocampal volume loss in first episode depression is consistent with a neurodevelopmental model of depression, advocating hippocampal structure as a potential diagnostic neurobiomarker for depression.

Introduction

Initial reports of hippocampal volume in depression suffered from limited resolution of early neuroimaging methods leading to poor separation of the hippocampus and adjacent structures (reviewed in: Fu et al., 2003). More recent meta-analyses have convincingly established that reduced hippocampal volume is a neurobiological feature of major depressive disorder, particularly in illnesses characterised by recurrent episodes and in chronic depression (Campbell and MacQueen, 2004, McKinnon et al., 2009, Videbech and Ravnkilde, 2004). However, the stage at which hippocampal atrophy begins in depression is unclear. In first episode depression, the evidence has been equivocal, with some studies observing decreased hippocampal volume (Cole et al., 2010, Frodl et al., 2002), while others have reported no significant difference (Eker et al., 2010, Kronmüller et al., 2009).

The presence of hippocampal atrophy from disease onset would have significant etiological and clinical implications as it would support a model of depression in which structural abnormalities appear earlier than previously believed with potentially deleterious effects on clinical outcome and response to antidepressant therapy (MacQueen and Frodl, 2010). In the present study, we sought to establish whether hippocampal atrophy exists from disease onset. We performed a random effects meta-analysis of magnetic resonance imaging studies of hippocampal volume in first episode depression.

Section snippets

Literature search

MEDLINE, EMBASE, Scopus and PsychINFO electronic databases were queried with the following search terms: “depression”, “major depressive disorder”, “magnetic resonance imaging”, “hippocampus”, and abbreviations “MDD”, “MRI”, “unipolar” for papers published between January 1990 and February 2011. References from the retrieved papers and reviews of hippocampal and regional brain volumes in major depressive disorder (MDD) were also inspected for relevant articles.

Inclusion criteria were: 1)

Results

A total of 7 independent studies (Cole et al., 2010, Eker et al., 2010, Kaymak et al., 2010, Kronmüller et al., 2009, MacQueen et al., 2003, Meisenzahl et al., 2010, van Eijndhoven et al., 2009) met our inclusion and exclusion criteria, reporting measurements of 191 patients with a first episode of depression (Table 1, additional methodological study characteristics in Supplementary Table A, Supplementary Table B). Briefly, all studies had recruited adult patients (mean age: 37.6 years, weighted

Discussion

The present meta-analysis establishes that hippocampal volume loss is not only a feature of recurrent and chronic depression but is also evident in adult patients with a first episode of the illness. Hippocampal volume reduction in first episode patients has also been recently demonstrated using whole-brain voxel-based morphometry (Zou et al., 2010). These findings can be linked with recent studies reporting smaller hippocampal volume in subjects at high risk for depression due to a family

Role of funding source

Funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

Conflict of interest

All authors declare that they have no conflicts of interests.

Acknowledgements

JC was supported by a Medical Research Council PhD studentship. SGC was supported by the National Institute for Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health award to the South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, King's College London.

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