Elsevier

Biological Psychiatry

Volume 56, Issue 2, 15 July 2004, Pages 101-112
Biological Psychiatry

Original article
Hippocampal volume, memory, and cortisol status in major depressive disorder: effects of treatment

https://doi.org/10.1016/j.biopsych.2004.04.002Get rights and content

Abstract

Background

Depression has been linked to stress, memory deficits, and hypercortisolemia. However, the relationships between depression, hippocampal structure and function, and cortisol levels are unclear and the effects of antidepressant treatment on the measures are not well studied.

Methods

Whole hippocampal volume, performance on verbal and visual declarative memory function and cortisol status was evaluated in 38 subjects with major depressive disorder (MDD) and 33 healthy subjects. All measures were repeated in a subgroup (n = 22) of depressed patients after successful selective serotonin reuptake inhibitor (SSRI) treatment.

Results

Hippocampal volume was not significantly different between patients with untreated MMD and healthy subjects, after controlling for whole brain volume, age and gender. However, depressed subjects had significantly greater deficits in delayed memory and percent retention on the verbal portion of the Wechsler Memory Scale—Revised (WMS-R) compared with healthy subjects, without significant differences in visual memory, attention, vigilance, or distractibility. Baseline plasma or urinary free cortisol (UFC) was not related to either hippocampal volume or memory deficits. Successful treatment with antidepressants did not change hippocampal volume but did result in a significant improvement in memory function and a reduction in UFC excretion.

Conclusions

Medication-free nonelderly depressed outpatients without alcohol dependence or adverse experiences in childhood had normal hippocampal volume. Focal declarative memory deficits in depression supported localized hippocampal dysfunction in depressed patients. Treatment with antidepressants significantly improved memory and depression but did not alter hippocampal volume, suggesting that antidepressants may improve hippocampal function in the absence of detectable structural changes.

Section snippets

Subjects

Outpatient depressed and healthy control subjects, 18–60 years of age, were recruited through newspaper advertisements and flyers and gave written informed consent before participation in this study. The study was approved by the Human Investigation Committee at the Yale University School of Medicine. After an initial psychiatric interview, all subjects underwent a physical examination and screening tests that included a complete blood count, plasma electrolytes, β-HCG and creatine, liver

Results

Sociodemographic and clinical information of depressed patients and healthy subjects are given in Table 1. Thirty-eight depressed patients (15 men, 23 women) and 33 healthy subjects (12 men, 21 women) formed the study sample. The mean age of the depressed patients was significantly higher than that of healthy subjects (41 ± 11 vs. 34 ± 10 years; F = 6.76, df = 1,69 p = .01). The height, weight, and education in years were not significantly different between patients and subjects. The gender

Discussion

In this study, patients with unipolar MDD demonstrated specific impairment in verbal memory, despite normal hippocampal volume. Urinary free cortisol (UFC) excretion and plasma cortisol levels in depressed patients were unrelated to either memory deficits or hippocampal volume. Immediate and delayed verbal memory improved and UFC decreased after successful treatment with antidepressant drugs without an accompanying increase in hippocampal volume.

A major finding of our study was the normal

Acknowledgements

We thank Sara Norris, M.P.H., for help with statistical analysis; Holly Giesen, B.A., for editorial assistance, Ryan Jerving, Ph.D., for help in preparing the manuscript, and Thomas Lam, M.D., for his contribution toward interrater reliability measurements for the hippocampus.

EV and GMA contributed equally to this paper.

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    This study was supported in part by National Institute of Mental Health grants MH-56120, MH-42088, MN-51761, and MH-58922; the Emory Conte Center for Early Life Stress; the National Alliance for Research on Schizophrenia and Depression (NARSAD); and an investigator-initiated research grant with Eli Lilly Pharmaceuticals.

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