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. 2015 Nov 1;78(9):635-46.
doi: 10.1016/j.biopsych.2014.09.002. Epub 2014 Sep 16.

Emotion-Dependent Functional Connectivity of the Default Mode Network in Adolescent Depression

Tiffany C Ho  1 , Colm G Connolly  2 , Eva Henje Blom  3 , Kaja Z LeWinn  2 , Irina A Strigo  4 , Martin P Paulus  5 , Guido Frank  6 , Jeffrey E Max  7 , Jing Wu  8 , Melanie Chan  7 , Susan F Tapert  9 , Alan N Simmons  10 , Tony T Yang  2
Affiliations

Emotion-Dependent Functional Connectivity of the Default Mode Network in Adolescent Depression

Tiffany C Ho et al. Biol Psychiatry. .

Abstract

Background: Functional magnetic resonance imaging research suggests that major depressive disorder (MDD) in both adults and adolescents is marked by aberrant connectivity of the default mode network (DMN) during resting state. However, emotional dysregulation is also a key feature of MDD. No studies to date have examined emotion-related DMN pathology in adolescent depression. Comprehensively understanding the dynamics of DMN connectivity across brain states in individuals with depression with short disease histories could provide insight into the etiology of MDD.

Methods: We collected functional magnetic resonance imaging data during an emotion identification task and during resting state from 26 medication-free adolescents (13-17 years old) with MDD and 37 well-matched healthy control subjects. We examined between-group differences in blood oxygenation level-dependent task responses and emotion-dependent and resting-state functional connectivity of the two primary nodes of the DMN: medial prefrontal cortex and posterior cingulate cortex (PCC). Additionally, we examined between-group differences in DMN functional connectivity and its relationship to depression severity and onset.

Results: Relative to healthy control subjects, unmedicated adolescents with MDD demonstrated reduced medial prefrontal cortex and PCC emotion-related deactivation and greater medial prefrontal cortex and PCC emotion-dependent functional connectivity with precuneus, cingulate gyrus, and striatum/subcallosal cingulate gyrus. The PCC-subcallosal cingulate connectivity remained inflexibly elevated in the subjects with MDD versus healthy control subjects during resting state. Stronger PCC emotion-dependent functional connectivity was associated with greater depression severity and an earlier age of depression onset.

Conclusions: Adolescent depression is associated with inflexibly elevated DMN connections. Given more recent evidence of DMN maturation throughout adolescence, our findings suggest that early-onset depression adversely affects normal development of functional brain networks.

Keywords: Adolescence; Default mode network; Functional connectivity; Functional magnetic resonance imaging; Major depressive disorder; Psychophysiologic interaction.

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Conflict of interest statement

Financial Disclosures All authors declare no potential biomedical or financial conflicts of interest.

Figures

Figure 1
Figure 1. Emotion identification task with dynamically morphing face stimuli
On FACE trials, a screen displaying text of the three possible emotions to discern (FEAR, HAPPY, SAD) was presented for 1500 ms. Next, a neutral face morphed smoothly and dynamically to an emotion of prototypical intensity over the span of 3000 ms. At maximal emotion intensity, the face then remained on the screen for an additional 800 ms of the trial before the screen turned blank for 700 ms (Figure 1A depicts an example face and is enlarged for purposes of clarity). At stimulus onset, two possible emotion choices were displayed in text on the bottom left and right corners; subjects were instructed to press one of two buttons corresponding to the displayed emotion as soon as they recognized the emotion of the face. As a sensorimotor control, we also had OVAL trials (6 s per trial), where subjects had to determine if the top of an oval was tilting to the left or right and make a button response accordingly as soon as they recognized the tilt direction (Figure 1B depicts a sample FACE and OVAL trial). See the supplement for more details.
Figure 2
Figure 2. Mean activation to each emotion type in the mPFC and PCC regions (i.e., seeds for the PPI analysis) showing significant between-group differences on the task (FACE-OVAL)
Mean percentage signal change to each condition (FEAR-OVAL, HAPPY-OVAL, SAD-OVAL) was extracted and subjected to post-hoc t-tests (Fisher's LSD). These post-hoc t-tests indicated a main effect of group at p<0.05 (denoted by *). These areas survived correction for multiple comparisons at a cluster-wise threshold of p<0.05. Locations are reported in MNI coordinates (radiological convention). See Figure S1 and Table S2 for a full summary of the between-group differences on the task.
Figure 3
Figure 3. Regions showing significant between-group differences in emotion-dependent functional connectivity of the mPFC seed
All areas survived correction for multiple comparisons at a cluster-wise threshold of p<0.05. Mean functional connectivity values are reported as Fisher's z-scores (Fz). The mean resting-state (RS) Fz were extracted from the regions exhibiting significant between-group differences on the psychophysiological interaction (PPI) analysis (see Methods for more details). Locations are reported in MNI coordinates (radiological convention). See also Table 2.
Figure 4
Figure 4. Regions showing significant between-group differences in emotion-dependent functional connectivity with the PCC seed
All areas survived correction for multiple comparisons at a cluster-wise threshold of p<0.05. Mean functional connectivity values are reported as Fisher's z-scores (Fz). The mean resting-state (RS) Fz were extracted from the regions exhibiting significant between-group differences on the psychophysiological interaction (PPI) analysis (see Methods for more details). Locations are reported in MNI coordinates (radiological convention). See also Table 3.
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