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Frontal white matter anisotropy and antidepressant remission in late-life depression.

ABSTRACT: 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.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.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.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.ClinicalTrials.gov NCT00339066.

SUBMITTER: Taylor WD

PROVIDER: S-EPMC2533397 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Frontal white matter anisotropy and antidepressant remission in late-life depression.

Taylor Warren D WD Kuchibhatla Maragatha M Payne Martha E ME Macfall James R JR Sheline Yvette I YI Krishnan K Ranga KR Doraiswamy P Murali PM

PloS one 20080924 9

<h4>Introduction</h4>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.<h4>Methods</h4>74 subjects with Major Depressive Disorder and age ...[more]

PMID: 18813343

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Project description:Patients with late-life depression (LLD) have a higher incident of developing dementia, especially individuals with memory deficits. However, little is known about the white matter characteristics of LLD with memory deficits (LLD-MD) in the human connectome, especially for the rich-club coefficient, which is an indicator that describes the organization pattern of hub in the network. To address this question, diffusion tensor imaging of 69 participants [15 LLD-MD patients; 24 patients with LLD with intact memory (LLD-IM); and 30 healthy controls (HC)] was applied to construct a brain network for each individual. A full-scale battery of neuropsychological tests were used for grouping, and evaluating executive function, processing speed and memory. Rich-club analysis and global network properties were utilized to describe the topological features in each group. Network-based statistics (NBS) were calculated to identify the impaired subnetwork in the LLD-MD group relative to that in the LLD-IM group. We found that compared with HC participants, patients with LLD (LLD-MD and LLD-IM) had relatively impaired rich-club organizations and rich-club connectivity. In addition, LLD-MD group exhibited lower feeder and local connective average strength than LLD-IM group. Furthermore, global network properties, such as the shortest path length, connective strength, efficiency and fault tolerant efficiency, were significantly decreased in the LLD-MD group relative to those in the LLD-IM and HC groups. According to NBS analysis, a subnetwork, including right cognitive control network (CCN) and corticostriatal circuits, were disrupted in LLD-MD patients. In conclusion, the disease effects of LLD were prevalent in rich-club organization. Feeder and local connections, especially in the subnetwork including right CCN and corticostriatal circuits, were further impaired in those with memory deficits. Global network properties were disrupted in LLD-MD patients relative to those in LLD-IM patients.

Project description:BACKGROUND:White matter hyperintensities (WMH) represent ischemic white matter damage in late-life depression (LLD) and are associated with cognitive control dysfunction. Understanding the impact of WMH on the structural connectivity of gray matter and the cognitive control correlates of WMH-related structural dysconnectivity can provide insight into the pathophysiology of LLD. METHODS:We compared WMH burden and performance on clinical measures of cognitive control in patients with LLD (N?=?44) and a control group of non-depressed older adults (N?=?59). We used the Network Modification (NeMo) Tool to investigate the impact of WMH on structural dysconnectivity in specific gray matter regions, and how such connectivity was related to cognitive control functions. RESULTS:Compared to the control group, LLD participants had greater WMH burden, poorer performance on Trail Making Test (TMT) A & B, and greater self-reported dysexecutive behavior on the Frosntal Systems Behavior Scale-Executive Function subscale (FrSBe-EF). Within the LLD group, disrupted connectivity in the left supramarginal gyrus, paracentral lobule, thalamus, and pallidum was associated with psychomotor slowing (TMT-A). Altered connectivity in the left supramarginal gyrus, paracentral lobule, precentral gyrus, postcentral gyrus, thalamus, and pallidum was associated with poor attentional set-shifting (TMT-B). A follow-up analysis that isolated set-shifting ability (TMT-B/A ratio) confirmed the association with dysconnectivity in the bilateral paracentral lobule, right thalamus, left precentral gyrus, postcentral gyrus, and pallidum; additionally, it revealed associations with dysconnectivity in the right posterior cingulate, and left anterior cingulate, middle frontal cortex, and putamen. CONCLUSIONS:In LLD, WMH are associated with region-specific disruptions in cortical and subcortical gray matter areas involved in attentional aspects of cognitive control systems and sensorimotor processing, which in turn are associated with slower processing speed, and reduced attentional set-shifting. CLINICAL TRIALS REGISTRATION:https://clinicaltrials.gov/ct2/show/NCT01728194.

Dataset Information

Frontal white matter anisotropy and antidepressant remission in late-life depression.

Publications

Frontal white matter anisotropy and antidepressant remission in late-life depression.

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