Macromolecular White Matter Abnormalities in Geriatric Depression: A Magnetization Transfer Imaging Study

Institute of Geriatric Psychiatry and the Department of Psychiatry, Weill Medical College of Cornell University, White Plains, NY, USA.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry (Impact Factor: 4.24). 05/2008; 16(4):255-62. DOI: 10.1097/JGP.0b013e3181602a66
Source: PubMed


Geriatric depression consists of complex and heterogeneous behaviors unlikely to be caused by a single brain lesion. However, abnormalities in specific brain structures and their interconnections may confer vulnerability to the development of late-life depression. The objective of this study was to identify subtle white matter abnormalities in late-life depression.
The authors used magnetization transfer ratio (MTR) imaging, a technique that is thought primarily to reflect myelin integrity, to examine the hypothesis that individuals with late-life depression would exhibit white matter abnormalities in frontostriatal and limbic regions.
The study was conducted in a university-based, geriatric psychiatry clinic.
Fifty-five older patients with major depression and 24 elderly comparison subjects were assessed.
Voxel-based analysis of MTR data were conducted with a general linear model using age as a covariate.
Relative to comparison subjects, patients demonstrated lower MTR in multiple left hemisphere frontostriatal and limbic regions, including white matter lateral to the lentiform nuclei, dorsolateral and dorsomedial prefrontal, dorsal anterior cingulate, subcallosal, periamygdalar, insular, and posterior cingulate regions. Depressed patients had lower MTR in additional left hemisphere locales including the thalamus, splenium of the corpus callosum, inferior parietal, precuneus, and middle occipital white matter regions.
These findings suggest that geriatric depression may be characterized by reduced myelin integrity in specific aspects of frontostriatal and limbic networks, and complement diffusion tensor studies of geriatric depression that indicate decreased organization of white matter fibers in specific frontal and temporal regions.

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    • "The method, quantified by the magnetization transfer ratio (MTR), which is a compound index of the exchange between free and protein-bound water protons pools, is regarded as superior to conventional MRI with respect to the detection and quantification of subtle white matter changes, e.g. in multiple sclerosis (Tofts et al., 2003). Studies using MT imaging in depression have revealed lower MTR in multiple white matter regions, including the fronto-striatal and limbic regions, and the genu and splenium of the corpus callosum (Gunning-Dixon et al., 2008; Kumar et al., 2004). "
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    ABSTRACT: Cerebral white matter lesions (WMLs) are believed to play an important role in a subset of major depression (MD). We aimed to describe the impact of WMLs on white matter pathways in MD using diffusion tensor imaging (DTI) and magnetization transfer imaging. As a novel approach, we used DTI tractography to assess pathways intersected by WMLs. We examined 22 patients with late-onset MD and 22 age- and gender-matched controls. Parametric maps of fractional anisotropy (FA), apparent diffusion coefficient (ADC), and magnetization transfer ratio (MTR) were obtained to describe tissue integrity. The association between depression severity and the tract-specific localization of WMLs was analyzed on a voxel-by-voxel basis. We showed a significant positive association between depression severity and fiber tracts intersected by WMLs in the left superior longitudinal fasciculus and the right uncinate fasciculus. In both groups, WMLs had significantly lower FA and MTR, and higher ADC than both the tracts they intersected and the normal-appearing white matter (NAWM). In turn, the tracts intersected by WMLs had significantly lower FA and higher ADC than the NAWM. In conclusion, depression severity correlates with the tract-specific localization of WMLs. WMLs have a pronounced effect on white matter integrity in the pathways they intersect.
    Full-text · Article · Oct 2010 · Psychiatry Research
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    • "Along with genetic factors, aging related changes compromising the integrity of frontolimbic circuitry may contribute to geriatric depression non-remission (Alexopoulos, 2005). Depressed elders have microstructural (Nobuhara et al., 2006) and macromolecular (Kumar et al., 2004; Gunning-Dixon et al., 2008) white matter abnormalities in frontolimbic pathways. White matter hyperintensities have been associated with chronicity of geriatric depression (Simpson et al., 1998), although some disagreement exists (Salloway et al., 2002). "
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    ABSTRACT: This study compared microstructural abnormalities in depressed elders and controls and studied the association of the serotonin transporter gene status to white matter abnormalities and to remission of depression. The subjects were Caucasians with non-psychotic major depression and normal elders. Depressed subjects received escitalopram 10 mg daily for 12 weeks. Remission was defined as a HDRS score of 7 or below for 2 consecutive weeks. Diffusion tensor imaging was performed and voxel-based analysis of fractional anisotropy (FA) was conducted using age and mean diffusivity as covariates. Depressed elders (N=27) had lower FA than controls (N=27) in several frontolimbic areas. Depressed elderly S-allele carriers also had lower FA than L homozygotes in frontolimbic brain areas, including the dorsal and rostral anterior cingulate, posterior cingulate, dorsolateral prefrontal and medial prefrontal regions, thalamus, and in other regions. S-allele carriers had a lower remission rate than L homozygotes. Small number of subjects, lack of random sampling, fixed antidepressant dose, short follow-up. Lower FA was observed in several frontolimbic and other regions in depressed elders compared to controls. Depressed S-allele carriers had both microstructural white matter abnormalities in frontolimbic networks and a low remission rate. It remains unclear whether the risk for chronicity of geriatric depression in S-allele carriers is mediated by frontolimbic compromise. However, these observations set the stage for studies aiming to identify the relationship of S allele to impairment in specific frontolimbic functions interfering with response of geriatric depression to antidepressants.
    Full-text · Article · May 2009 · Journal of Affective Disorders
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    • "The present study further demonstrates the sensitivity of MTI in revealing gray matter MTR reductions in young and middle-aged TRD patients. Previous MTI investigations into human depressive disorders have focused on geriatric depression (Kumar et al., 2004; Gunning-Dixon et al., 2008; Wyckoff et al., 2003) but our results are not directly comparable due to differences in data analysis. "
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    ABSTRACT: Studies on treatment resistant depression (TRD) using advanced magnetic resonance imaging techniques are very limited. A group of 15 patients with clinically defined TRD and 15 matched healthy controls underwent magnetization transfer imaging (MTI) and T1-weighted (T1W) imaging. MTI data were processed and analyzed voxel-wised in SPM2. A voxel based morphometric (VBM) analysis was performed using T1W images. Reduced magnetization transfer ratio was observed in the TRD group relative to normal controls in the anterior cingulate, insula, caudate tail and amygdala-parahippocampal areas. All these regions were identified within the right hemisphere. VBM revealed no morphological abnormalities in the TRD group compared to the control group. Negative correlations were found between MRI and clinical measures in the inferior temporal gyrus. The cross-sectional design and small sample size. The findings suggest that MTI is capable of identifying subtle brain abnormalities which underlie TRD and in general more sensitive than morphological measures.
    Full-text · Article · Mar 2009 · Journal of Affective Disorders
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