Structural Neuroimaging Research Methods in Geriatric Depression

doi:10.1097/01.JGP.0000238588.34205.bd

The American Journal of Geriatric Psychiatry

Volume 14, Issue 10, October 2006, Pages 812-822

https://doi.org/10.1097/01.JGP.0000238588.34205.bd Get rights and content

Geriatric depression consists of complex and heterogeneous behaviors unlikely to be caused by a single brain lesion. However, there is evidence that abnormalities in specific brain structures and their interconnections confer vulnerability to the development of late-life depression. Structural magnetic resonance imaging methods can be used to identify and quantify brain abnormalities predisposing to geriatric depression and in prediction of treatment response. This article reviews several techniques, including morphometric approaches, study of white matter hyperintensities, diffusion tensor imaging, magnetization transfer imaging, t2 relaxography, and spectroscopy, that have been used to examine these brain abnormalities with a focus on the type of information obtained by each method as well as each method's limitations. The authors argue that the available methods provide complementary information and that, when combined judiciously, can increase the knowledge gained from neuroimaging findings and conceptually advance the field of geriatric depression.

Section snippets

Manual Morphometry

The most common method to examine differences in brain morphometry in vivo is the use of T1-weighted images. Most morphometric studies have depended on manual measurements of regions of interest (ROI). These studies provide measures of the volume of specific brain areas and have the advantage that the boundaries used are typically guided by relevant neuroanatomic parameters. The reliability of such measures tends to be high, at least within a particular laboratory or among a small set of

White Matter Hyperintensities

The most common method to study WM neuropathology on MRI has been the examination of WM hyperintensities (WMH). These hyperintensities are typically observed in T2-weighted or fluid-attenuated inversion recovery sequences and are taken to indicate WM damage. WMH are more prevalent and severe in older depressed individuals than age-matched control subjects and mainly occur in subcortical regions and frontal WM projections.²⁴ Subcortical hyperintensities have been found to be associated with

CONCLUSION

Although the etiology of geriatric depression is unknown, there is consensus that diverse processes (e.g., vascular lesions, impaired neurogenesis, inflammation, genetics), alone or in synergy, disrupt certain brain structures and confer vulnerability to depression.² Frontostriatal structures, the hippocampus, and the amygdala are structures whose functional disruption is thought to predispose to geriatric depression. WM pathology may interfere with functional communication among these

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Late-life major depression (LLD) is characterized by distinct epidemiologic and psychosocial factors, as well as medical comorbidities that are associated with specific neuroanatomical differences. The purpose of this study was to use interregional correlations of cortical and subcortical volumes to examine cortical-subcortical structural network properties in subjects with LLD compared with healthy comparison subjects.
This was a cross-sectional neuroimaging study conducted in the general community. We recruited 73 healthy elderly comparison subjects and 53 subjects with LLD who volunteered in response to advertisements. Brain network connectivity measures were generated by correlating regional volumes after controlling for age, gender, and intracranial volume by using the Brain Connectivity Toolbox.
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Citation Excerpt :
For those with MDD, it has been shown that hippocampal volume is smaller than in healthy subjects.45 Similarly, a reduction in hippocampal volume in late-life depression has also been reported by many investigators46–49 and has been further supported by meta-analyses performed in two separate studies.45,50 In a positive emission tomography study, de Asis et al.51 demonstrated deficits in bilateral activation of hippocampus of the geriatric depressed patients.
Brain-derived neurotrophic factor (BDNF), one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons, synaptic integrity, and synaptic plasticity. Evidence suggests that BDNF is involved in major depression, such that the level of BDNF is decreased in depressed patients and that antidepressants reverse this decrease. Stress, a major factor in depression, also modulates BDNF expression. These studies have led to the proposal of the neurotrophin hypothesis of depression. Late-life depression is associated with disturbances in structural and neural plasticity as well as impairments in cognitive behavior. Stress and aging also play a crucial role in late-life depression. Many recent studies have suggested that not only expression of BDNF is decreased in the serum/plasma of patients with late-life depression, but structural abnormalities in the brain of these patients may be associated with a polymorphism in the BDNF gene, and that there is a relationship between a BDNF polymorphism and antidepressant remission rates. This review provides a critical review of the involvement of BDNF in major depression, in general, and in late-life depression, in particular.
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Citation Excerpt :
In addition to volume reduction, disruption of white matter integrity has been reported recently in MDD (Abe et al., 2010; Kieseppä et al., 2010; Shimony et al., 2009). These studies show that abnormalities in specific brain structures and their interconnections may confer vulnerability to the development of late-life depression (Hoptman et al., 2006). Recently, the incidence of “minor depression” or “subclinical depression,” which is milder in symptomatology or duration than MDD, has been increasing and has received attention (Lavretsky and Kumar, 2002).
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This study is supported by grant RO1 MH65653 (Alexopoulos), P30 MH68638 (Alexopoulos), by grant RO1 MH60662 (KOL), by K23 MH074818 (FGD), K23 MH067702 (CFM), R01 MH64783 (MJH), and by the Sanchez Foundation.

Dr. Alexopoulos has received research grants by Forest Pharmaceuticals, Inc., and Cephalon and participated in scientific advisory board meetings of Forest Pharmaceuticals. He has given lectures supported by Forest, Cephalon, Bristol Meyers, Janssen, Pfizer, and Lilly and has received support by Comprehensive Neuroscience, Inc. for the development of treatment guidelines in late-life psychiatric disorders.

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Special ArticleStructural Neuroimaging Research Methods in Geriatric Depression

Section snippets

Manual Morphometry

White Matter Hyperintensities

CONCLUSION

Biol Psychiatry

Lancet

Neuropsychopharmacology

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Neuroimage

Neuroimage

Behav Brain Res

Magn Reson Imaging

J Neurosci Methods

International Congress Series

Biol Psychiatry

Biophys J

Neurobiol Aging

Biol Psychiatry

Neuroimage

Neuroimage

Neuroimage

Neuroimage

Psychiatry Res

J Magn Reson

J Magn Reson

Neuroimage

Psychiatry Res

Psychiatry Res

The basics of MRI. 2006

Magnetic Resonance Imaging: Physical Principles and Sequence Design

Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: an MRI-based parcellation of the prefrontal cortex

Am J Psychiatry

Neuroanatomical substrates of depression in the elderly

Eur Arch Psychiatry Clin Neurosci

Amygdala core nuclei volumes are decreased in recurrent major depression

Neuroreport

Antidepressant exposure may protect against decrement in frontal gray matter volumes in geriatric depression

J Clin Psychiatry

Voxel based morphometry—the methods

Hum Brain Mapp

‘Voxel-based morphometry’ should not be used with imperfectly registered images

Neuroimage

A fully automatic multimodality image registration algorithm

J Comput Assist Tomogr

Automated image registration: I. General methods and intrasubject, intramodality validation

J Comput Assist Tomogr

Brain morphometric abnormalities in geriatric depression: long-term neurobiological effects of illness duration

Am J Psychiatry

Subcortical hyperintensity on magnetic resonance imaging: a comparison of normal and depressed elderly subjects

Am J Psychiatry

Neuropsychological correlates of white-matter lesions in healthy elderly subjects. A threshold effect

Arch Neurol

The relation of white matter hyperintensities to implicit learning in healthy older adults

Int J Geriatr Psychiatry

Severe deep white matter lesions and outcome in elderly patients with major depressive disorder: follow up study

BMJ

Is subcortical disease associated with a poor response to antidepressants? Neurological, neuropsychological and neuroradiological findings in late-life depression

Psychol Med

Special Article
Structural Neuroimaging Research Methods in Geriatric Depression