Background: Longitudinal neuroimaging studies of major depressive disorder (MDD) have most commonly
assessed the effects of antidepressants from the serotonin reuptake inhibitor class and usually reporting a single
measure. Multimodal neuroimaging assessments were acquired from MDD patients during an acute depressive
episode with serial measures during a 12-week treatment with the serotonin-norepinephrine reuptake inhibitor
(SNRI) duloxetine.
Methods: Participants were medication-free MDD patients (n = 32; mean age 40.2 years) in an acute depressive
episode and healthy controls matched for age, gender, and IQ (n = 25; mean age 38.8 years). MDD patients received
treatment with duloxetine 60 mg daily for 12 weeks with an optional dose increase to 120 mg daily after 8 weeks.
All participants had serial imaging at weeks 0, 1, 8, and 12 on a 3 Tesla magnetic resonance imaging (MRI) scanner.
Neuroimaging tasks included emotional facial processing, negative attentional bias (emotional Stroop), resting state
functional MRI and structural MRI.
Results: A significant group by time interaction was identified in the anterior default mode network in which
MDD patients showed increased connectivity with treatment, while there were no significant changes in healthy
participants. In the emotional Stroop task, increased posterior cingulate activation in MDD patients normalized
following treatment. No significant group by time effects were observed for happy or sad facial processing,
including in amygdala responsiveness, or in regional cerebral volumes. Reduced baseline resting state connectivity
within the orbitofrontal component of the default mode network was predictive of clinical response. An early
increase in hippocampal volume was predictive of clinical response.
Conclusions: Baseline resting state functional connectivity was predictive of subsequent clinical response.
Complementary effects of treatment were observed from the functional neuroimaging correlates of affective
facial expressions, negative attentional bias, and resting state. No significant effects were observed in affective
facial processing, while the interaction effect in negative attentional bias and individual group effects in resting
state connectivity could be related to the SNRI class of antidepressant medication. The specificity of the observed
effects to SNRI pharmacological treatments requires further investigation.
Trial registration: Registered at clinicaltrials.gov (NCT01051466)
