Magnetic resonance imaging in late-life depression: multimodal examination of network disruption.

CONTEXT

Disruption of frontal-subcortical and limbic networks is hypothesized to have a key role in late-life depression (LLD) and can be examined using magnetic resonance imaging (MRI) techniques. Gray matter can be examined using T1-weighted MRI, white matter using T2-weighted MRI and diffusion tensor imaging, and functional connectivity in resting-state networks using functional MRI. Although independent MRI studies have supported gray and white matter abnormalities in frontosubcortical and limbic networks and increased functional connectivity in the default-mode network in depression, no study has concurrently examined gray matter, white matter, and functional connectivity.

OBJECTIVE

To examine whether results of different MRI techniques are complementary, multimodal MRI was used to compare gray matter, white matter, and resting-state networks between LLD and control groups.

DESIGN

Cross-sectional, case-control, multimodal MRI analysis.

SETTING

University research department.

PARTICIPANTS

Thirty-six recovered participants with LLD (mean age, 71.8 years) and 25 control participants (mean age, 71.8 years).

MAIN OUTCOME MEASURES

Gray matter was examined across the whole brain using voxel-based morphometry. Subcortical gray matter structures were also automatically segmented, and volumetric and shape analyses were performed. For white matter analysis, fractional anisotropy, axial diffusivity, and radial diffusivity values were examined using tract-based spatial statistics. For resting-state network analysis, correlation coefficients were compared using independent components analysis followed by dual regression.

RESULTS

White matter integrity was widely reduced in LLD, without significant group differences in gray matter volumes or functional connectivity.

CONCLUSIONS

The present work strongly supports the hypothesis that white matter abnormalities in frontal-subcortical and limbic networks play a key role in LLD even in the absence of changes in resting functional connectivity and gray matter. Factors that could contribute to the lack of significant differences in gray matter and functional connectivity measures, including current symptom severity, medication status, and age of participants with LLD, are discussed.