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Genomic predictors of remission to antidepressant treatment in geriatric depression using genome-wide expression analyses: a pilot study.

ABSTRACT: This first pilot study of genome-wide expression as predictor of antidepressant response in late-life depression examined genome-wide transcriptional profiles in a randomized placebo-controlled trial of combined methylphenidate and citalopram.Genome-wide transcriptional profiles were examined in peripheral blood leukocytes sampled at baseline and 16 weeks from 35 older adults with major depression, who were randomized to methylphenidate?+?citalopram, citalopram?+?placebo, or methylphenidate + placebo. Methylphenidate doses ranged between 10 and 40 mg/day, and citalopram doses ranged between 20 and 60 mg/day. Remission was defined as Hamilton Depression Rating Scale score of 6 or below. Early remission was achieved in the first 4 weeks of treatment. We hypothesized that differential gene expression at baseline can predict antidepressant response.We analyzed gene expression in 24 remitters and 11 non-remitters. At baseline, we found three genes showing higher expression in all remitters versus non-remitters that satisfied the established level of significance: a fold change of 2 and p-value of 0.05 that included HLA-DRB5, SELENBP1, and LOC388588. Two gene transcripts showed higher expression in early remitters at baseline compared with non-remitters. The first gene was CA1 carbonic anhydrase gene, on chromosome 8 involved in respiratory function (fold change 2.54; p = 0.03). The second gene was the SNCA-?-synuclein gene, implicated, which binds to dopamine transporter (fold change 2.1; p = 0.03).Remission to antidepressants in geriatric depression may be associated with a particular gene expression profile in monoaminergic and metabolic pathways and needs to be replicated in a larger sample.

SUBMITTER: Eyre HA

PROVIDER: S-EPMC5567872 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Genomic predictors of remission to antidepressant treatment in geriatric depression using genome-wide expression analyses: a pilot study.

Eyre Harris A HA Eskin Ascia A Nelson Stanley F SF St Cyr Natalie M NM Siddarth Prabha P Baune Bernhard T BT Lavretsky Helen H

International journal of geriatric psychiatry 20151015 5

<h4>Objective</h4>This first pilot study of genome-wide expression as predictor of antidepressant response in late-life depression examined genome-wide transcriptional profiles in a randomized placebo-controlled trial of combined methylphenidate and citalopram.<h4>Methods</h4>Genome-wide transcriptional profiles were examined in peripheral blood leukocytes sampled at baseline and 16 weeks from 35 older adults with major depression, who were randomized to methylphenidate + citalopram, citalopram ...[more]

PMID: 26471432

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Project description: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.

Dataset Information

Genomic predictors of remission to antidepressant treatment in geriatric depression using genome-wide expression analyses: a pilot study.

Publications

Genomic predictors of remission to antidepressant treatment in geriatric depression using genome-wide expression analyses: a pilot study.

Similar Datasets

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