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

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

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.

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / physiopathology*
  • Comorbidity
  • Connectome / methods*
  • Depressive Disorder, Major / diagnostic imaging
  • Depressive Disorder, Major / epidemiology
  • Depressive Disorder, Major / physiopathology*
  • Fear / physiology*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Reward*
  • Stress Disorders, Post-Traumatic / diagnostic imaging
  • Stress Disorders, Post-Traumatic / epidemiology
  • Stress Disorders, Post-Traumatic / physiopathology*