TY - JOUR
T1 - Identifying predictors, moderators, and mediators of antidepressant response in major depressive disorder
T2 - Neuroimaging approaches
AU - Phillips, Mary L.
AU - Chase, Henry W.
AU - Sheline, Yvette I.
AU - Etkin, Amit
AU - Almeida, Jorge R C
AU - Deckersbach, Thilo
AU - Trivedi, Madhukar H.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - Objective: Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. Method: In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. Results:Theauthorsfirsthighlight themostconsistentfindings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergicallymodulated reward neural circuitry, centered onthe ventral striatumandmedial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specificmeasures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Conclusions: Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter-and longer-term clinical and functional outcomes.
AB - Objective: Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. Method: In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. Results:Theauthorsfirsthighlight themostconsistentfindings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergicallymodulated reward neural circuitry, centered onthe ventral striatumandmedial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specificmeasures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Conclusions: Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter-and longer-term clinical and functional outcomes.
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U2 - 10.1176/appi.ajp.2014.14010076
DO - 10.1176/appi.ajp.2014.14010076
M3 - Review article
C2 - 25640931
AN - SCOPUS:84922241944
SN - 0002-953X
VL - 172
SP - 124
EP - 138
JO - American Journal of Psychiatry
JF - American Journal of Psychiatry
IS - 2
ER -