TY - JOUR
T1 - Differential response to SSRI versus Placebo and distinct neural signatures among data-driven subgroups of patients with major depressive disorder
AU - Chin Fatt, Cherise R.
AU - Cooper, Crystal M.
AU - Jha, Manish K.
AU - Minhajuddin, Abu
AU - Rush, A. John
AU - Trombello, Joseph M.
AU - Fava, Maurizio
AU - McInnis, Melvin
AU - Weissman, Myrna
AU - Trivedi, Madhukar H.
N1 - Funding Information:
The EMBARC study was supported by the National Institute of Mental Health of the National Institutes of Health under award numbers U01MH092221 (Trivedi, M.H.) and U01MH092250 (McGrath, P.J., Parsey, R.V., Weissman, M.M.). The corresponding author had full access to all study data and had final responsibility for the decision to submit the paper for publication. This work was also funded in part by the Hersh Foundation (Trivedi MH PI). We appreciate the editorial support of Jon Kilner, MS, MA (Pittsburgh), who was funded by the Center for Depression Research and Clinical Care (Trivedi MH PI).
Publisher Copyright:
© 2020
PY - 2021/3/1
Y1 - 2021/3/1
N2 - Objective:: To identify data-driven subgroups in Major Depressive Disorder (MDD) in order to elucidate underlying neural correlates and determine if these subgroups have utility in predicting response to antidepressant versus placebo. Methods:: Using 27 clinical measures at baseline of Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study, participants with MDD (n=244) were sub grouped using principal component (PC) analysis. Baseline-to-week-8 changes in depression severity with sertraline versus placebo were compared in these subgroups. Resting-state functional connectivity of these subgroups were compared to those of healthy controls (n=38). Results:: Eight subgroups were identified from four PCs: (PC1) severity of depression-associated symptoms, (PC2) sub-threshold mania and anhedonia, (PC3) childhood trauma, medical comorbidities, and sexual dysfunction, and (PC4) personality traits of openness and agreeableness. Participants with high childhood trauma experienced greater improvement with sertraline (Cohen's d=0.87), whereas those with either higher levels of subthreshold hypomanic symptoms (Cohen's d=0.67) or with lower levels of agreeableness and openness experienced greater improvement with placebo (Cohen's d=0.71). Participants with high childhood trauma had greater connectivity between salience and dorsal attention networks, whereas those with higher levels of subthreshold hypomanic symptoms and lower levels of agreeableness and openness had greater connectivity within limbic network and that of visual network with hippocampus and dorsal attention network. Conclusion:: Assessing history of childhood trauma, presence of subthreshold hypomanic symptoms and personality traits may help to identify subgroups of patients with MDD who respond differentially to sertraline or placebo and have distinct neural signatures.
AB - Objective:: To identify data-driven subgroups in Major Depressive Disorder (MDD) in order to elucidate underlying neural correlates and determine if these subgroups have utility in predicting response to antidepressant versus placebo. Methods:: Using 27 clinical measures at baseline of Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study, participants with MDD (n=244) were sub grouped using principal component (PC) analysis. Baseline-to-week-8 changes in depression severity with sertraline versus placebo were compared in these subgroups. Resting-state functional connectivity of these subgroups were compared to those of healthy controls (n=38). Results:: Eight subgroups were identified from four PCs: (PC1) severity of depression-associated symptoms, (PC2) sub-threshold mania and anhedonia, (PC3) childhood trauma, medical comorbidities, and sexual dysfunction, and (PC4) personality traits of openness and agreeableness. Participants with high childhood trauma experienced greater improvement with sertraline (Cohen's d=0.87), whereas those with either higher levels of subthreshold hypomanic symptoms (Cohen's d=0.67) or with lower levels of agreeableness and openness experienced greater improvement with placebo (Cohen's d=0.71). Participants with high childhood trauma had greater connectivity between salience and dorsal attention networks, whereas those with higher levels of subthreshold hypomanic symptoms and lower levels of agreeableness and openness had greater connectivity within limbic network and that of visual network with hippocampus and dorsal attention network. Conclusion:: Assessing history of childhood trauma, presence of subthreshold hypomanic symptoms and personality traits may help to identify subgroups of patients with MDD who respond differentially to sertraline or placebo and have distinct neural signatures.
KW - Clinical
KW - Data Driven
KW - Major Depressive Disorder
KW - SSRI
KW - Subgroups
KW - fMRI
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U2 - 10.1016/j.jad.2020.12.102
DO - 10.1016/j.jad.2020.12.102
M3 - Article
C2 - 33445082
AN - SCOPUS:85099207327
SN - 0165-0327
VL - 282
SP - 602
EP - 610
JO - Journal of affective disorders
JF - Journal of affective disorders
ER -