title: Childhood maltreatment and combat posttraumatic stress differentially predict fear-related fronto-subcortical connectivity.
abstract: BACKGROUND
  Adult posttraumatic stress disorder (PTSD) has been characterized by altered fear-network connectivity. Childhood trauma is a major risk factor for adult PTSD, yet its contribution to fear-network connectivity in PTSD remains unexplored. We examined, within a single model, the contribution of childhood maltreatment, combat exposure, and combat-related posttraumatic stress symptoms (PTSS) to resting-state connectivity (rs-FC) of the amygdala and hippocampus in military veterans.
  
  
  METHODS
  Medication-free male veterans (n = 27, average 26.6 years) with a range of PTSS completed resting-state fMRI. Measures including the Clinician-Administered PTSD Scale (CAPS), Childhood Trauma Questionnaire (CTQ), and Combat Exposure Scale (CES) were used to predict rs-FC using multilinear regression. Fear-network seeds included the amygdala and hippocampus.
  
  
  RESULTS
  Amygdala: CTQ predicted lower connectivity to ventromedial prefrontal cortex (vmPFC), but greater anticorrelation with dorsal/lateral PFC. CAPS positively predicted connectivity to insula, and loss of anticorrelation with dorsomedial/dorsolateral (dm/dl)PFC. Hippocampus: CTQ predicted lower connectivity to vmPFC, but greater anticorrelation with dm/dlPFC. CES predicted greater anticorrelation, whereas CAPS predicted less anticorrelation with dmPFC.
  
  
  CONCLUSIONS
  Childhood trauma, combat exposure, and PTSS differentially predict fear-network rs-FC. Childhood maltreatment may weaken ventral prefrontal-subcortical circuitry important in automatic fear regulation, but, in a compensatory manner, may also strengthen dorsal prefrontal-subcortical pathways involved in more effortful emotion regulation. PTSD symptoms, in turn, appear to emerge with the loss of connectivity in the latter pathway. These findings suggest potential mechanisms by which developmental trauma exposure leads to adult PTSD, and which brain mechanisms are associated with the emergence of PTSD symptoms.
authors.affiliation: Psychiatry, University of Wisconsin School of Medicine & Public Health, Madison, WI.|Medical Physics, University of Wisconsin School of Medicine & Public Health, Madison, WI.
authors.forename: Rasmus M
authors.initials: RM
authors.lastname: Birn
authors.affiliation: Medical Physics, University of Wisconsin School of Medicine & Public Health, Madison, WI.
authors.forename: Rémi
authors.initials: R
authors.lastname: Patriat
authors.affiliation: Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Phillips
authors.affiliation: Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Anne
authors.initials: A
authors.lastname: Germain
authors.affiliation: Psychiatry, University of Wisconsin School of Medicine & Public Health, Madison, WI.|Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Herringa
mesh_terms: D000328:Adult; D054523:Adult Survivors of Child Abuse / Q000523:psychology*; D000679:Amygdala / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology; D003130:Combat Disorders / Q000503:physiopathology*; D005239:Fear; D005625:Frontal Lobe / Q000503:physiopathology*; D059907:Functional Neuroimaging; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology*; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology*; D014728:Veterans / Q000523:psychology*; D055815:Young Adult
keywords: PTSD; abuse; brain imaging; functional MRI; maltreatment; trauma