Antidepressants Normalize the Default Mode Network in Patients With Dysthymia

Figure 1. Whole-brain resting-state functional-connectivity maps with seed region in the posterior cingulate cortex. Qualitatively, the connectivity maps demonstrate the commonly observed connectivity pattern of the default mode network in both the participants with dysthymic disorder (DD; N = 41) (A) and in the healthy control participants (N = 25) (B). C, Comparison of the 2 groups demonstrated that the participants with DD had stronger connections from the posterior cingulate cortex to the mesial prefrontal cortex (mPFC) bilaterally, lateral parietal lobes (LPC) bilaterally, and precuneus (PC). See Table 2 for statistical significance.

Figure 2. Graphical presentation of the default mode network (DMN). Pretreatment magnetic resonance imaging scans were obtained in participants with dysthymic disorder (N = 41) and matched healthy control subjects (N = 25). Posttreatment magnetic resonance imaging scans were obtained following a 10-week clinical trial of duloxetine vs placebo. The dots represent DMN regions and the lines represent functional connections (threshold z >0.2); line width corresponds to the connection strength. Qualitatively, in the pretreatment scans, the DMN demonstrates more and stronger connections in the dysthymic vs healthy control participants. Statistical comparison using graph theory (network density) bears out this observation (see Table 2). Posttreatment scans demonstrate a treatment × time interaction (F_1,29 = 5.0; P = .03), driven by a greater reduction in DMN connectivity in the duloxetine-treated vs placebo-treated participants (N = 15 and N = 17, respectively). PCC indicates posterior cingulate cortex.

Figure 3. Comparison of the pretreatment and posttreatment scans demonstrated a treatment × time interaction (F_1,29 = 5.0; P = .03) in the connection density of the default mode network (DMN). Specifically, mean DMN density in the placebo arm (N = 17) was similar in the baseline vs follow-up scans (mean [SD] baseline density, 0.21 [0.08]; mean [SD] follow-up density, 0.19 [0.08]), but there was a significant reduction in the DMN density in the duloxetine arm (N = 15) (mean [SD] baseline density, 0.24 [0.06]; mean [SD] follow-up density, 0.16 [0.06]; change in density: t = 4.0; P = .002). Post hoc testing demonstrated that in the duloxetine arm, the DMN density in the follow-up scans was comparable with healthy control subjects (N = 25) (t = 0.4; P = .90). The error bars indicate standard errors.

Figure 4. Connection strength between the posterior cingulate cortex (PCC) and left amygdala (peak voxel Montreal Neurological Institute coordinates: x = −18, y = −4, z = −22) predicted depressive symptoms on the Hamilton Depression Rating Scale (HAM-D) (r = 0.65; P < .001; cluster size, 503 voxels) in patients with dysthymia (N = 41). The connection strength between the PCC and the right amygdala was also a predictor of HAM-D scores (r = 0.58; P < .001; peak voxel Montreal Neurological Institute coordinates: x = 36, y = 0, z = −26; cluster size, 43 voxels), but this finding did not reach both arms of our statistical threshold. Coronal slice displayed at y = −4.