Elsevier

Biological Psychiatry

Volume 49, Issue 9, 1 May 2001, Pages 803-806
Biological Psychiatry

Original article
Medial orbital frontal lesions in late-onset depression

https://doi.org/10.1016/S0006-3223(00)01113-6Get rights and content

Abstract

Background: Early studies using magnetic resonance (MR) imaging suggested that subcortical vascular changes are more prevalent in late-life depression and that they may play a role in the pathophysiology of depression. Studying the location of the lesion relative to the occurrence of depression could be critical in delineating the neuroanatomic substrates of depression. Our purpose was to characterize these lesions in terms of location by development of statistical parametric maps of lesions that differentiate patients from control subjects.

Methods: Magnetic resonance images were acquired on 88 elderly depressed subjects (“patients,” unipolar major depression assessed using the Duke Depression Evaluation Schedule, age range 63–80 years) enrolled in the Duke University Clinical Research Center for the Study of Late-Life Depression and 47 age- and gender-matched nondepressed subjects (“control subjects”). The MR protocol includes a volumetric, dual-contrast fast spin–echo pulse sequence. A statistical parametric map was formed from a two-group t test to test for differences in lesion density between patients and control subjects. Additional testing was performed to evaluate whether there were regions that correlated with the severity of depression using the 17-item Hamilton Depression rating.

Results: The statistical parametric mapping analysis between groups showed two major regions of increased lesion density in the patients in the medial orbital prefrontal white matter. Severity of depression among depressed patients was correlated with lesions in the medial orbital region.

Conclusions: This study supports recent evidence implicating the medial orbital frontal cortex in depression.

Introduction

The causes of depression in the elderly are poorly understood (Byrum et al 1999). Genetic factors are of less significance in patients presenting with depression for the first time late in life (Krishnan et al 1997). Thus, other factors are believed to play a role in the etiopathophysiology of late-onset depression. Early studies using magnetic resonance imaging (MRI) suggested that subcortical vascular changes are more prevalent in late-life depression and that they may play a role in the pathophysiology of depression (Krishnan et al 1997). The importance of these changes has also been demonstrated in a recent epidemiologic study (Steffens et al 1999). Studying the location of the lesion relative to the occurrence of depression could be critical in delineating the neuroanatomic substrates of depression. The purpose of this study was to characterize these lesions in terms of location by development of statistical parametric maps of lesions that differentiate patients from control subjects.

Section snippets

Methods and materials

Magnetic resonance images were acquired for 88 elderly depressed subjects (age range 63–80 years, 63 female), assessed using the Duke Depression Evaluation Schedule (George et al 1989) and enrolled in the Duke University Clinical Research Center for the Study of Late-Life Depression, and 47 age- and gender-matched nondepressed subjects (control subjects) after obtaining written informed consent under a protocol approved by the Duke Institutional Review Board. All patients met DSM-IV criteria

Results

There was a higher rate of vascular disease in the control subjects (34) who were recruited to have a greater risk for vascular disease than in patients (38; χ2 = 10.8, p < .001). Subcortical hyperintensity was greater in patients than in control subjects (0 and 1 vs. 2 and 3; χ2 = 7.32, p < .006). Large deep white matter hyperintensities were also greater in depressed patients, although this did not reach significance (3 vs. rest, χ2 = 2.85, p < .09). The SPM analysis between groups showed two

Discussion

This study, in conjunction with other literature on the role of this part of the prefrontal cortex, suggests a critical role for these lesions in the pathophysiology of depression in late life. Previous studies with rating scales have provided evidence that large lesions, especially in the frontal cortex and basal ganglia, are related to depression. This study is the first to more precisely localize the lesions. The regions identified are consistent with other data in the literature (Ongur et

Acknowledgements

This study was sponsored by the National Institute of Mental Health (Grant No. MH40159).

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