title: Altered resting state functional connectivity of fear and reward circuitry in comorbid PTSD and major depression.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  Comorbid PTSD-MDD may be associated with multifaceted functional connectivity alterations in both fear and reward systems. Clinical implications are discussed.
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Liat
authors.initials: L
authors.lastname: Helpman
authors.affiliation: Department of Psychology and Institute for Mental Health Research, The University of Texas at Austin, Austin, TX, USA.
authors.forename: Santiago
authors.initials: S
authors.lastname: Papini
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Franklin
authors.initials: F
authors.lastname: Schneier
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Markowitz
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: Page E
authors.initials: PE
authors.lastname: Van Meter
authors.affiliation: Department of Biostatistics, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Lindquist
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
authors.forename: Tor D
authors.initials: TD
authors.lastname: Wager
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Neria
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D015897:Comorbidity; D063132:Connectome / Q000379:methods*; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000503:physiopathology*; D005239:Fear / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012201:Reward; D013313:Stress Disorders, Post-Traumatic / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000503:physiopathology*
keywords: MDD; PTSD; amygdala; depression; fear processing; nucleus accumbens; resting state functional connectivity; reward processing