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. 2017 Jul;34(7):641-650.
doi: 10.1002/da.22594. Epub 2016 Dec 28.

Altered resting state functional connectivity of fear and reward circuitry in comorbid PTSD and major depression

Xi Zhu  1   2 , Liat Helpman  1   2 , Santiago Papini  3 , Franklin Schneier  1   2 , John C Markowitz  1   2 , Page E Van Meter  1 , Martin A Lindquist  4 , Tor D Wager  5 , Yuval Neria  1   2
Affiliations

Altered resting state functional connectivity of fear and reward circuitry in comorbid PTSD and major depression

Xi Zhu et al. Depress Anxiety. 2017 Jul.

Abstract

Background: Individuals with comorbid posttraumatic stress disorder and major depressive disorder (PTSD-MDD) often exhibit greater functional impairment and poorer treatment response than individuals with PTSD alone. Research has not determined whether PTSD-MDD is associated with different network connectivity abnormalities than PTSD alone.

Methods: We used functional magnetic resonance imaging (fMRI) to measure resting state functional connectivity (rs-FC) patterns of brain regions involved in fear and reward processing in three groups: patients with PTSD-alone (n = 27), PTSD-MDD (n = 21), and trauma-exposed healthy controls (TEHCs, n = 34). Based on previous research, seeds included basolateral amygdala (BLA), centromedial amygdala (CMA), and nucleus accumbens (NAcc).

Results: Regardless of MDD comorbidity, PTSD was associated with decreased connectivity of BLA-orbitalfrontal cortex (OFC) and CMA-thalamus pathways, key to fear processing, and fear expression, respectively. PTSD-MDD, compared to PTSD-alone and TEHC, was associated with decreased connectivity across multiple amygdala and striatal-subcortical pathways: BLA-OFC, NAcc-thalamus, and NAcc-hippocampus. Further, while both the BLA-OFC and the NAcc-thalamus pathways were correlated with MDD symptoms, PTSD symptoms correlated with the amygdala pathways (BLA-OFC; CMA-thalamus) only.

Conclusions: Comorbid PTSD-MDD may be associated with multifaceted functional connectivity alterations in both fear and reward systems. Clinical implications are discussed.

Keywords: MDD; PTSD; amygdala; depression; fear processing; nucleus accumbens; resting state functional connectivity; reward processing.

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Conflict of interest statement

CONFLICT OF INTEREST

Drs. Zhu, Helpman, Van Meter, Lindquist, Wager, and Mr. Papini, report no biomedical financial interests or potential conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Centromedial amygdala (CMA) (right and left, Red) and basolateral amygdala (BLA) (right and left, blue) seed ROIs. The underlying brain template is from FSL MNI152 standard-space T1-weighted average structural template image
FIGURE 2
FIGURE 2
Decreased BLA-OFC, CMA-THA connectivity were found in PTSD, when compared with TEHC (p < .05, FDR-corrected)
FIGURE 3
FIGURE 3
Rs-FC of BLA-OFC, CMA-THA, NAcc-THA, and NAcc-HIP for PTSD-MDD, PTSD-alone, and TEHC groups. ANCOVA revealed significant differences among the three groups in NAcc-THA (F(2,81) = 5.5, pFDR < .05), and NAcc-HIP (F(2,81) = 3.9, pFDR < .05) connections. Significant connectivity revealed by post hoc ANCOVA tests were marked as asterisk (*)
FIGURE 4
FIGURE 4
Correlations between CAPS scores and rs-FC of BLA-OFC (r=−0.288, p ≤ .006) (left) and CMA-THA (r=−0.234, p ≤ .006) (right) in all PTSD participants (PTSD-alone and PTSD-MDD combined). NAcc-THA (r=−0.12) and NAcc-HIP (r=−0.078) were not correlated with CAPS total score in all PTSD participants. Blue dot: PTSD-alone, green dot: PTSD-MDD
FIGURE 5
FIGURE 5
Correlations between HAMD total and FC of BLA-OFC (r=−0.324, p ≤ .006) (left) and NAcc-THA (r=−0.342, p ≤ .006) (right) in all PTSD participants (PTSD-alone and PTSD-MDD combined). NAcc-HIP (r = −0.213, p = .056) and CMA-THA (r = −0.061, p = .589) did not reach significant. Blue dot: PTSD-alone, Green dot: PTSD-MDD
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