The present study investigated amygdalar morphometry (size and shape) of elderly individuals diagnosed with major depression. Previous studies have examined volumetric differences in LLD, but to our knowledge this is the first study to also examine amygdalar shape variation in LLD. Our results suggest that the size of the amygdalae in depressed, elderly individuals do not undergo significant changes as compared to healthy, elderly individuals. This is in agreement with some previous studies in major depression (Bremner et al., 2000
; Mervaala et al., 2000
; Munn et al., 2007
), questionable dementia (Hensel et al., 2005
), recurrent major depression (Sheline et al., 1998
), and depression without psychosis (Keller et al., 2008
). We also found a trend towards unilateral decreased volume in the left amygdala, which has been observed in depression with memory problems (Gunten et al., 2000
). However, our volumetric results differ from other mood disorder studies that have found amygdalar volumetric differences (increases and decreases), e.g. (Altshuler et al., 1998
; Bellis et al., 2000
; Frodl et al., 2002
; Frodl et al., 2003
; Hastings et al., 2004
; Lange and Irle, 2004
; Xia et al., 2004
; Hensel et al., 2005
; Rosso et al., 2005
; Velakoulis et al., 2006
; Keller et al., 2008
Mixed amygdalar volumetric findings may be explained by a variety of technical factors including differences in MRI image resolution, diagnosis heterogeneity, neuroanatomical amygdalae definition, amygdalae boundary delineation protocol, head and/or brain size normalization, etc. Additionally, demographic and clinical variables should be considered as covariates during statistical analysis. Demographic and clinical variables to be considered include, but are not limited to age, gender, education, medication usage, illness duration and course, substance abuse, history of physical or emotional abuse, etc. Moreover, the co-occurence of other medical conditions should probably also be considered such as the presence of vascular lesions, white matter hyperintensities, diabetes, cortisol dysregulation, etc. These factors could contribute to the differing amygdalar volumetric results in mood disorder studies.
A variety of amygdalar volumetric studies have identified variables that are correlated with volume changes, but, again, the findings remain mixed. Another potential cause of these inconsistencies may be the non-differentiation between the various sub-types of depression. For example, among the previous studies, fewer than half focused on major depression and none of those focused on the elderly. The only study focused on the elderly subjects was a dementia study conducted by Hensel et al. (2005)
. Therefore, we believe that without fully accounting for deviations in technical protocol, and fully controlling and exploring demographics and clinical variables, it would be unwise to directly compare our volumetric results to those of other studies.
We believe that, in addition to various technical, clinical and demographic factors, reported volumetric discrepancies might partly be due to an inherent limitation in considering a gross measure of size. Shape analysis provides for better specificity over volume delivering a spatial map of localized regions affected by a pathology, which may be used to link local structural differences to other measures. Several published research studies have investigated shape variation in other structures believed to be complicit in psychiatric illnesses. Thompson et al. (2004)
developed an analytical method to quantify the progression of hippocampal and ventricular change in Alzheimer’s disease (AD), finding that temporal horn expansion was a strong indication of AD progression. Shen et al. (2005)
studied hippocampal shape differences in mild cognitive impairment and found that structural changes are primarily located in the anterior right hippocampus and posterior left hippocampus. Styner et al. (2005)
studied structural differences of the lateral ventricles in schizophrenia and found that, although volumetric differences were insignificant, the locality of the observed shape difference in the anterior and posterior regions of the lateral ventricles is under genetic influence in both healthy controls and schizophrenia patients.
In the present study, we tested the hypothesis that amygdalar shape differences may be apparent even when overall volumes are inconsistently altered. Resulting statistical maps revealed significant structural differences at multiple regions of both amygdalae. Specifically, there were dispersed regions of significant contraction in the LLD subjects as compared to the control subjects despite insignificant volumetric differences. The primary regions exhibiting contraction were the basolateral nuclei for both the left and right amaygdalae. A comprehensive description for the neurobiological basis of the observed shape changes was outside of the scope of this study. However, investigators have previously found a decrease in the size of the basolateral nuclei, (e.g. Sheline et al., 1998
) attributing the volume loss to neuronal degeneration as a result of glutamate excitotoxicity associated with hypercortisolemia, which may be exemplified by overactivity of the amygdalae in depression (Drevets, 2001
The basolateral nuclei play a key role in emotion recognition in neurobiologic models of depression. The basolateral nuclei receive afferent neural connections from the hippocampus, entorhinal cortex, sensory thalamus and cortex, polymodal cortex, and medial prefrontal cortex, etc., and sends efferent neural connections to the prefrontal cortex, polymodal cortex, and ventral striatum, etc. Many functional and structural neuroimaging studies have found that these structures are significantly different in LLD (Nobler et al., 1999
; Kumar et al., 2000
; Steffens et al., 2000
; Alexopoulos, 2002
; Bell-McGinty et al., 2002
; Aizenstein et al., 2005
). Therefore, it is possible that, in LLD, morphologic changes of the basolateral nuclei may directly affect the connectivity with these regions and cause neuronal damage to them or vice versa.
- Published volumetric (size) studies of the amygdalae in mood disorders have been inconclusive with reports of increased, decreased, and no volume change for patients relative to controls.
- Many reasons may explain these volumetric discrepancies such as delineation precision. However, it can be hypothesized that shape differences may be apparent even though overall volumes may be inconsistent. This hypothesis was tested in this study by examining the morphometry (size and shape) of the amygdalae in LLD.
- Despite insignificant volumetric findings, local shape differences were detected with the most prominent change being contraction in the LLD subjects as compared to the control subjects in a region typically associated with the basolateral nuclei.
- It is believed that studying shape differences of the amygdalae and other brain structures may help better understand the neurobiology of LLD and other mood disorders.