fMRI response to negative words and SSRI treatment outcome in major depressive disorder: A preliminary study

Abstract

Clinically useful predictors of treatment outcome in major depressive disorder (MDD) remain elusive. We examined associations between functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) signal during active negative word processing and subsequent selective serotonin reuptake inhibitor (SSRI) treatment outcome in MDD. Unmedicated MDD subjects (n=17) performed an emotional word processing fMRI task, and then received eight weeks of standardized antidepressant treatment with escitalopram. Lower pre-treatment BOLD responses to negative words in midbrain, dorsolateral prefrontal cortex, paracingulate, anterior cingulate, thalamus and caudate nuclei correlated significantly with greater improvement following escitalopram treatment. Activation of these regions in response to negative words correlated significantly with reaction time for rating word relevance. Maximally predictive clusters of voxels identified using a cross-validation approach predicted 48% of the variance in response to treatment. This study provides preliminary evidence that SSRIs may be most beneficial in patients who are less able to engage cognitive control networks while processing negative stimuli. Differences between these findings and previous fMRI studies of SSRI treatment outcome may relate to differences in task design. Regional BOLD responses to negative words predictive of SSRI outcome in this study were both overlapping and distinct from those predictive of outcome with cognitive behavioral therapy (CBT) in previous studies using the same task. Future studies may examine prediction of differential outcome across treatments in the context of a randomized controlled trial.

Neural Predictors of Treatment Response in Depression

“…Remitters were found to have higher 5-HT 1A binding in the raphe nuclei compared with non-remitters, although there were no differences in neural areas known to be innervated by serotonin neurones. This finding was interpreted in line with the idea that SSRIs may be most effective in those with increased 5-HT 1A autoreceptor function, who are most likely to experience increased serotonin efflux once these receptors are desensitized as part of repeated SSRI treatment [23]. These effects did not correlate with the DTI findings in the same sample above [8], suggesting they may tap into separate aspects of function.…”

“…Another recent study used an emotion-based task as a predictor of treatment response to 8 weeks of escitalopram in 17 patients with depression [23], based on an overlapping patient sample to the DTI study reported above [8]. Lower blood oxygen level-dependent (BOLD) responses to negative stimuli across a large network (including the dorsolateral prefrontal cortex [DLPFC], subgenual ACC, insula, posterior cingulate, caudate, and thalamus) were correlated with improvement following subsequent antidepressant drug treatment.…”

Diagnostic and therapeutic utility of neuroimaging in depression: an overview

“…Furthermore, one recent study found that patients with higher baseline activity in the ACC while viewing emotional words was associated with poorer response to treatment,72 contradicting findings from previous studies. Although there are some inconsistencies in findings, these are likely a result of confounding factors such as differences in sample characteristics and the type of intervention used.…”

Computational neuroimaging strategies for single patient predictions

“…This has shown some promising recent results, indicating that it may become possible to predict individual trajectories of patients with schizophrenia (Anticevic et al, 2015) or mood disorders (Lythe et al, 2015;Schmaal et al, 2015) from neuroimaging data, or forecast individual treatment responses to psychotherapy (Mansson et al, 2015), antidepressants (DeBattista et al, 2011;McGrath et al, 2013;Miller et al, 2013) and antipsychotics (Hadley et al, 2014;Nejad et al, 2013).…”