Differential effects of antidepressant treatment on long-range and short-range functional connectivity strength in patients with major depressive disorder

Abstract

Although we have some basic understanding of the neurochemical mechanisms of the antidepressants, the network-level effect of antidepressant treatment is still not fully understood. This study was conducted to investigate the effects of antidepressant on functional brain networks of patients with major depressive disorder (MDD). We performed resting-state fMRI scans on 20 first-episode drug-naive MDD patients at baseline and after escitalopram medication for 8 weeks. Twenty healthy controls also received MRI scans with an 8-week interval. The graph theory indices, long- and short-range functional connectivity strength (FCS), were computed to characterize the brain connectivity. The analysis of covariance was conducted on FCS maps of patients and controls to obtain the interaction effect of group and time, which indicate treatment-related effect. Following treatment, increased long-range FCS in the bilateral posterior cingulate cortex/precuneus and right thalamus in MDD patients at baseline were reduced. Meanwhile, increased short-range FCS in the bilateral ventromedial prefrontal cortex and left amygdala in patients were reduced, while reduced short-range FCS in the right parahippocampal gyrus was increased. Results suggest that the brain regions associated with negative emotional processing and regulation, and self-referential function could be modulated by escitalopram treatment; long- and short-range FCS are differentially affected by antidepressant.

Figure 1

Long-range and short-range FCS patterns. (A) Mean long-range FCS maps in the healthy control (HC) and MDD groups at baseline and week 8. (B) Mean short-range FCS maps in the HC and MDD groups at the two time points. The color bars represent the connectivity strength.

Figure 2

Group × time interaction on long-range FCS. (A) The imaging map presents the brain regions showing significant group × time interaction on long-range FCS, including the bilateral posterior cingulate cortex (PCC/precuneus) and the right thalamus. The Gaussian random field theory was used for multiple comparison correction with a cluster threshold of p < 0.05 and z > 2.3. (B) The bar maps showing between-groups and within-group differences in the clusters showing significant group × time interaction on long-range FCS. The data were expressed as mean value + SD. **p < 0.01, ***p < 0.001.

Figure 3

Group × time interaction on short-range FCS. (A) The imaging map presents the regions showing significant group × time interaction on short-range FCS, including the bilateral ventromedial prefrontal cortex (vmPFC), left amygdala, and right parahippocampal gyrus (PHG). The Gaussian random field theory was used for multiple comparison correction with a cluster threshold of p < 0.05 and z > 2.3. (B) The bar maps showing between-groups and within-group differences in the clusters showing significant group × time interaction on short-range FCS. The data were expressed as mean value + SD. *p < 0.05, **p < 0.01.

Figure 4

Correlation between change of lFCS of bilateral PCC and change in depressive severity. The scatter map shows significant correlation of the changes of lFCS of bilateral PCC with reduction rate of HRSD scores (HRSD_0w − HRSD_8w/HRSD_0w*100%) from week 0 to week 8. lFCS: long-range functional connectivity strength; PCC: posterior cingulate cortex; HRSD: Hamilton Rating Scale for Depression.