Frontal white matter anisotropy and antidepressant remission in late-life depression.
BACKGROUND
Neuroanatomic features associated with antidepressant treatment outcomes in older depressed individuals are not well established. This study used diffusion tensor imaging to examine frontal white matter structure in depressed subjects undergoing a 12-week trial of sertraline. We hypothesized that remission would be associated with higher frontal anisotropy measures, and failure to remit with lower anisotropy.


METHODS
74 subjects with Major Depressive Disorder and age 60 years or older were enrolled in a twelve-week open-label trial of sertraline and completed clinical assessments and 1.5T magnetic resonance brain imaging. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in regions of interest placed in the white matter of the dorsolateral prefrontal cortex, anterior cingulate cortex, and corpus callosum. Differences in ADC and FA values between subjects who did and did not remit to treatment over the study period were assessed using generalized estimating equations, controlling for age, sex, medical comorbidity and baseline depression severity.


RESULTS
Subjects who did not remit to sertraline exhibited higher FA values in the superior frontal gyri and anterior cingulate cortices bilaterally. There were no statistically significant associations between ADC measures and remission.


CONCLUSIONS
Failure to remit to sertraline is associated with higher frontal FA values. Functional imaging studies demonstrate that depression is characterized by functional disconnection between frontal and limbic regions. Those individuals where this disconnection is related to structural changes as detected by DTI may be more likely to respond to antidepressants.


BACKGROUND
ClinicalTrials.gov NCT00339066.
Taylor
Warren D
WD
The Department of Psychiatry, Durham, North Carolina, USA. taylo066@mc.duke.edu
Kuchibhatla
Maragatha
M
Payne
Martha E
ME
Macfall
James R
JR
Sheline
Yvette I
YI
Krishnan
K Ranga
KR
Doraiswamy
P Murali
PM
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D016880:Anisotropy; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D001931:Brain Mapping; D003866:Depressive Disorder / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D020280:Sertraline / Q000494:pharmacology*
D000928:Antidepressive Agents; D020280:Sertraline