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 structures and create vulnerability to geriatric depression. This model postulates that vulnerability to geriatric depression is not created by a single lesion or a failing of a single brain structure but by a state of disruption that can be created by diverse brain abnormalities. Accordingly, several models of predisposition to geriatric depression have been advanced, and each may account for a significant percentage of vulnerable patients.1
Central to testing hypotheses related to structurally based vulnerability to geriatric depression is the availability of neuroimaging techniques. The diversity of extant structural neuroimaging modalities allows assessment of various aspects of brain structures and WM regions implicated in geriatric depression. From the clinical point of view, structural neuroimaging has begun to identify subgroups of depressed elders resistant to traditional treatments. Understanding the underlying mechanisms can guide the development of novel therapeutic approaches.2
The advances in technology, however, do not lessen the importance of rigorous study design. Hypothesis-specific decisions must be made about appropriate comparison groups or regions and must also consider how individual variation in lesion location, for example, might be obscured by averaging methods.
Each MR imaging approach is best suited to provide information about some aspects of brain structures but not others. However, the information derived from different imaging approaches can be complementary and lead to a coherent understanding of brain dysfunction contributing to depression. For example, volumetric assessment demonstrated reduced caudate9
volumes in depression as well as components of frontolimbic pathways.6
A recent study offered preliminary evidence of reduced magnetization transfer in the neostriatum of depressed elders suggesting demyelination and axonal degeneration.67
T2 maps have shown a larger volume of WM hyperintensities in geriatric depressives compared with normal elders.82
DTI studies documented microstructural abnormalities in WM of frontolimbic pathways. Both WM hyperintensities and microstructural abnormalities have been associated with executive dysfunction, and all three predict poor antidepressant response.2,27–30,49,83–85
Therefore, although each approach offers limited information, converging findings support the hypothesis that frontolimbic integrity is critical for antidepressant response.
Clear hypotheses that consider the technical and interpretative strengths and limitations of the proposed methods can leverage the recent advances in structural imaging techniques despite existing technical and interpretive shortcomings. The richness of current structural neuroimaging methods allows the advancement of hypotheses that could not be conceived before these technical developments. Therefore, clear understanding of what structural neuroimaging can and cannot measure reliably, and the strategic use of such information, is central for the conceptual advancement of the field of geriatric depression.