Elsevier

Biological Psychiatry

Volume 47, Issue 12, June 2000, Pages 1087-1090
Biological Psychiatry

Brief report
Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study

https://doi.org/10.1016/S0006-3223(99)00296-6Get rights and content

Abstract

Background: Previous studies have shown that major depression is frequently accompanied by hypercortisolemia. There is some evidence suggesting that an increase in the glucocorticoid levels may make hippocampal cells more vulnerable to insults caused by hypoxia, hypoglycemia, or excitatory neurotransmitters. Using magnetic resonance imaging (MRI), the hippocampi of patients with major depression were measured and compared with values observed in control subjects.

Methods: Thirty-eight patients with primary unipolar major depression were recruited. Twenty control subjects were matched for age, gender, and years of education. The hippocampal volume was measured from coronal MRI scans in all of the subjects. Patients were also grouped and compared as responders and nonresponders to treatment with fluoxetine of 20 mg/day, for 8 weeks. Hamilton Depression Rating Scale (HDRS) was used to determine the severity of depression.

Results: No significant differences were observed between the hippocampal volumes of patients with major depression and control subjects; however, a significant correlation was observed between the left hippocampal volume of men and their HDRS baseline values. In addition, female responders had a statistically significant higher mean right hippocampal volume than nonresponders.

Conclusions: The results of our study indicate no reduction in the volume of the hippocampus in patients with major depression. Nonetheless, the results do suggest that the effects of disease severity, gender, and treatment response may influence hippocampal volume.

Introduction

Although there seems to be a consensus on the observed abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis in patients with major depression, changes in the volume of the hippocampus in depressed subjects is a topic of debate. It has been hypothesized that increased levels of glucocorticoids may lead to cognitive impairments related to the pathology of the hippocampus (Sapolsky et al 1986). Sapolsky (1992) discussed the proposed mechanisms by which high levels of glucocorticoids increase neuronal cell death in the hippocampus, which may lead to impairments of learning and memory. Based on this premise, one might expect a reduction in the volume of the hippocampus in those with hypercortisolemia, found in a group of patients with major depression.

Using magnetic resonance imaging, several groups have examined volumetric changes in the hippocampus of those with major depression. Some have found no difference between the hippocampal volume of nonpsychiatric control subjects and that of patients with major depression (Axelson et al 1993; Coffey et al 1993). On the other hand, Sheline et al (1996) reported smaller left and right hippocampal volumes in patients with major depression.

In one study, the depressed group was divided into two subtypes based on the individual’s response to treatment (Pillay et al 1997). They analyzed volumetric changes in cerebral and cerebellar regions. Although they did not find significant differences when comparing depressed patients as a whole with control subjects, they did find significant results when depressed subjects were divided into groups of responders and nonresponders.

We therefore hypothesized a reduction in the volume of the hippocampus in subjects with major depression in comparison with control subjects and also examined whether differences existed between responders and nonresponders.

Section snippets

Human subjects

After approval of the study by the Institutional Review Board of Massachusetts General Hospital, written informed consent was obtained from all subjects. Thirty-eight consecutively referred patients with primary unipolar major depression were recruited in the open phase of an NIMH-sponsored double-blind study of fluoxetine treatment, 20 mg/day, for 8 weeks. All depressed patients met the criteria for major depressive disorder, determined with the Structured Clinical Interview for Diagnosis

Results

Analysis of variance comparing left and right hippocampal volumes of the major depressed patients to the left and right hippocampal volumes of the control subjects revealed no statistically significant differences (Table 1). Repeated measures ANOVAs revealed no statistically significant differences between the volumes of the left and right hippocampus in both the 20 control subjects and the 38 patients with major depression. In addition, no significant difference was observed when the ratios

Discussion

The comparison of absolute hippocampal volumes or the comparison of the ratios of hippocampal volumes to cerebral volumes between the 20 control subjects and the 38 patients with major depression revealed no statistically significant differences (Table 1).

The results presented here do not replicate the findings (Sheline et al 1996) of a reduction in the hippocampal volume of patients with major depression. These results are in accordance with findings of Coffey et al (1993) and Axelson et al

Acknowledgements

This work was supported in part by the National Alliance for Research on Schizophrenia and Depression and The Stanley Foundation.

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