Regular Research Articles
One-Year Change in Anterior Cingulate Cortex White Matter Microstructure: Relationship With Late-Life Depression Outcomes

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Objective

Differences in white matter structure measured with diffusion tensor imaging (DTI) are associated with late-life depression, but results examining how these differences relate to antidepressant remission are mixed. To better describe these relationships, the authors examined how 1-year change in DTI measures are related to 1-year course of depression.

Design

One-year cross-sectional follow-up to a 12-week clinical trial of sertraline.

Setting

Outpatients at an academic medical center.

Participants

Twenty-nine depressed and 20 never-depressed elderly subjects. Over the 1-year period, 16 depressed subjects achieved and maintained remission, whereas 13 did not.

Measurements

One-year change in fractional anisotropy (FA) and diffusivity in frontal white matter, as measured by DTI.

Results

Contrary to our hypotheses, depressed subjects who did not remit over the study interval exhibited significantly less change in anterior cingulate cortex (ACC) white matter FA than did never-depressed or depressed-remitted subjects. There were no group differences in other frontal or central white matter regions. Moreover, there was a significant positive relationship between change in Montgomery-Asberg Depression Rating Scale (MADRS) and change in ACC FA, wherein greater interval decline in FA was associated with greater interval decline in MADRS.

Conclusion

Older depressed individuals who remit exhibit white matter changes comparable with what is observed in never-depressed individuals, whereas nonremitters exhibit significantly less change in ACC FA. Such a finding may be related to either antidepressant effects on brain structure or the effects of chronic stress on brain structure. Further work is needed to better understand this relationship.

Section snippets

Sample

Participants were initially recruited via advertisements and outpatient clinical referrals at Duke University Medical Center to participate in a 12-week study examining the relationship among hyperin-tense lesions, cognition, and 12-week response to sertraline.18, 19 Entry criteria for this parent study included meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depressive disorder (MDD) without psychosis by the Structured Clinical

RESULTS

As previously reported,18 74 depressed subjects enrolled in the original 12-week trial of sertraline had evaluable DTI data. Thirty-six of those subjects either refused to participate in this follow-up study or were lost to follow-up. Of the 38 individuals who did enroll, DTI scan data were not processable for nine individuals, primarily because the MRI being ended early or difficulties with image registration. This resulted in a sample of 29 individuals who were depressed at entry into the

DISCUSSION

Our primary finding was that the cohort of subjects who were depressed at study entry and did not remit over the following 1-year period exhibited less change in ACC white matter FA than did either nondepressed subjects or depressed subjects who remitted. There was no significant difference in ACC FA change between the nondepressed and remitted subjects. Moreover, we found a statistically significant positive correlation between change in ACC FA and change in MADRS score over 1 year, wherein a

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  • Cited by (0)

    We acknowledge Cynthia R. Key for preparing and preprocessing of DTI data and Kulpreet Singh for assistance with the figure.

    This work was supported by NIMH grants R01 MH078216 and R01 MH074916.

    Drs. Taylor and MacFall and Mr. Boyd have no conflicts to report. Dr. Payne has received speaking honoraria from Eli Lilly (Taiwan). Dr. Sheline reports serving on the Eli-Lilly Speakers Bureau. Dr. Krishnan has received consultancy fees from CeNeRx, Corcept, Glaxo-SmithKline, Johnson & Johnson, Merck, Roche, and Son-exa. He has ownership interest in Orexigen, CeNeRx, and Sonexa. Dr. Doraiswamy has received research grants and honoraria for consulting or speaking from several pharmaceutical companies and antidepressant manufacturers and has stock in Sonexa Therapeutics.

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