Regional White Matter Integrity Predicts Treatment Response to Escitalopram and Memantine in Geriatric Depression

A Pilot Study

Bibliographic Data

ID15527684
AuthorsBeatrix Krause (0000-0001-5495-6348, University of California, Los Angeles), Prabha Siddarth (0000-0001-8746-6353, University of California, Los Angeles), Michaela M Milillo (0000-0003-1370-8297, University of California, Los Angeles), Roza Vlasova (0000-0002-6455-8949, University of California, Los Angeles), Linda M Ercoli (University of California, Los Angeles), Katherine L Narr (0000-0002-9396-7936, University of California, Los Angeles), Helen Lavretsky (0000-0001-9990-5085, University of California, Los Angeles, corresponding author)
Year2020
Volume11
Pages548904-548904
Publication date2020-11-17
Open AccessYes
TypeARTICLE
VenueFrontiers in Psychiatry (JOURNAL)
Journal identifiersISSN: 1664-0640 • E-ISSN: 1664-0640
PublisherFrontiers Media (PUBLISHER • CH)
DOI10.3389/fpsyt.2020.548904
PMID33329088
OpenAlexW3100423237
LanguageEN
References cited15

Background: Geriatric depression with subjective memory complaints increases the risk for Alzheimer's Disease. Memantine, a neuroprotective drug, can improve depression and help prevent cognitive decline. In our 6-months clinical trial, escitalopram/memantine (ESC/MEM) improved mood and cognition compared to escitalopram/placebo treatment (ESC/PBO; NCT01902004). In this report, we investigated whether baseline brain white matter integrity in fronto-limbic-striatal tracts can predict clinical outcomes using fractional anisotropy (FA). Methods: Thirty-eight older depressed adults (mean age = 70.6, SD = 7.2) were randomized to ESC/MEM or ESC/PBO and underwent diffusion-weighted imaging (DWI) at 3 Tesla at baseline. Mood was assessed using the Hamilton Depression Rating Scale (HAMD), apathy using the Apathy Evaluation Scale (AES) and anxiety using the Hamilton Anxiety Scale (HAMA) at baseline and 6-months follow-up. FA was extracted from seven tracts of interest (six in each hemisphere and one commissural tract) associated with geriatric depression. Non-parametric General Linear Models were used to examine group differences in the association between FA and symptom improvement, controlling for age, sex, baseline symptom scores and scanner model, correcting for false discovery rate (FDR). Post-hoc tests further investigated group differences in axial, mean and radial diffusivity (AD, MD, and RD, respectively). Lastly, we performed an exploratory whole-brain model to test whether FA might be related to treatment response with memantine. Results: There were no differences in remission rates or HAMD change between groups. In bilateral anterior and posterior internal capsule tracts and bilateral inferior and right superior fronto-occipital (IFO and SFO) fasciculus, higher FA was associated with larger improvements in depressive symptoms for ESC/MEM, but not ESC/PBO, correcting for FDR. Lower MD in the left IFO and RD in the right anterior internal capsule were associated with improved treatment responses. We found no significant associations in the whole-brain analysis. Limitations: Included small sample size and high dropout. Conclusions: Higher baseline FA and lower RD and MD in hypothesized fronto-limbic-striatal tracts predicted greater improvement in mood and anxiety with ESC/MEM compared to ESC/PBO in geriatric depression. FA as a biomarker for white matter integrity may serve as a predictor of treatment response but requires confirmation in larger future studies

Antidepressant · Anxiety · Apathy · Cognition · Dementia · Depression (economics · Disease · Escitalopram · Fractional anisotropy · Geriatric Depression Scale · Magnetic resonance imaging · Memantine · Psychiatry · White matter · Advanced Neuroimaging Techniques and Applications · Advanced NMR Techniques and Applications · Functional Brain Connectivity Studies · Medicine · Psychology · Internal Medicine

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