Striatal Functional Connectivity Alterations After Two-Week Antidepressant Treatment Associated to Enduring Clinical Improvement in Major Depressive Disorder

Abstract

Background: Only less than 40% of patients with Major depressive disorder (MDD) can achieve remission after several weeks of initial antidepressant treatment. Predicting whether the prescribed treatment is effective in the following course may help clinicians modify the treatment regimen in time, and reduce the staggering burden for patients and society. However, there are not yet reliable markers based on neurobiological change after a treatment regimen steadily applied, for predicting clinical treatment outcome. The striatal circuits often exhibit abnormality for MDD patients, and are implicated in antidepressant treatments. Methods: Nineteen first-episode drug-naive MDD patients (nine females, mean age was 30 years old) were recruited to undergo clinical symptom assessment and resting state fMRI scanning at baseline, after 2 and 8 weeks of treatment with duloxetine. A seed-based analysis was used to obtain functional connectivity (FC) maps of six sub-regions of the stratum, then we explored the relationship of 2-week changes of striatal FC with clinical symptom improvement after 8-week duloxetine treatment. Results: The results revealed that 2-week FC changes of the striatal cognitive and affective subdivisions with the frontoparietal regions positively correlated with 8-week symptom improvement. We also found that early FC changes between the striatal motor subdivision and the motor-related cortical regions negatively correlated with later symptom improvement. Conclusions: These findings suggest that change of the FC of the cortical-striatal circuits at the early stage of treatment is critical for later remission of MDD. Furthermore, the association between the FC change and symptom improvement may have significant implication for clinical practice to regard neural changes as reference for evaluating how antidepressant treatment works.

Keywords: antidepressant; clinical improvement; major depressive disorder; prediction; striatum.

Figure 1

Association of 2-week ΔFC of striatum with 8-week symptom improvement. The image shows the brain regions whose 2-week functional connectivity alterations with different striatal subdivisions (in color) were positively (A) and negatively (B) correlated with 8-week symptom improvement, and shows the seed locations of the striatal subdivisions (C). On the right are scatters showing examples of positive association (ΔFC of left DC and right MFG, indicated by a grey arrow) and negative association (ΔFC of right DRP and right PCG). DC, dorsal caudate; VSs, superior ventral striatum; DRP, dorsal rostral putamen; VRP, ventral rostral putamen; ΔFC, functional connectivity alteration.

Figure 2

Association of 2-week ΔFC within the network with 8-week symptom improvement. The schematic image shows positive and negative association of functional connectivity changes between different striatal subdivisions with the regions in cortical networks defined by Yeo et al. (40). The positive association mainly involves the striatal subdivision and cortical networks for high-order cognitive processing, while the negative association mainly involves those for visual and motor processing.