title: Early life stress and the anxious brain: evidence for a neural mechanism linking childhood emotional maltreatment to anxiety in adulthood.
abstract: BACKGROUND
  Childhood emotional maltreatment (CEM) increases the likelihood of developing an anxiety disorder in adulthood, but the neural processes underlying conferment of this risk have not been established. Here, we test the potential for neuroimaging the adult brain to inform understanding of the mechanism linking CEM to adult anxiety symptoms.
  
  
  METHODS
  One hundred eighty-two adults (148 females, 34 males) with a normal-to-clinical range of anxiety symptoms underwent structural and functional magnetic resonance imaging while completing an emotion-processing paradigm with facial expressions of fear, anger, and happiness. Participants completed self-report measures of CEM and current anxiety symptoms. Voxelwise mediation analyses on gray-matter volumes and activation to each emotion condition were used to identify candidate brain mechanisms relating CEM to anxiety in adulthood.
  
  
  RESULTS
  During processing of fear and anger faces, greater amygdala and less right dorsolateral prefrontal (dlPFC) activation partially mediated the positive relationship between CEM and anxiety symptoms. Greater right posterior insula activation to fear also partially mediated this relationship, as did greater ventral anterior cingulate (ACC) and less dorsal ACC activation to anger. Responses to happy faces in these regions did not mediate the CEM-anxiety relationship. Smaller right dlPFC gray-matter volumes also partially mediated the CEM-anxiety relationship.
  
  
  CONCLUSIONS
  Activation patterns of the adult brain demonstrate the potential to inform mechanistic accounts of the CEM conferment of anxiety symptoms. Results support the hypothesis that exaggerated limbic activation to negative valence facial emotions links CEM to anxiety symptoms, which may be consequent to a breakdown of cortical regulatory processes.
authors.affiliation: Department of Psychiatry & Behavioral Sciences,Stanford University,Stanford, CA,USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Fonzo
authors.affiliation: Department of Clinical Effectiveness Research,Patient-Centered Outcomes Research Institute,Washington, DC,USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Ramsawh
authors.affiliation: Department of Psychiatry,University of California San Diego,La Jolla,CA,USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Flagan
authors.affiliation: Department of Psychiatry,University of California San Diego,La Jolla,CA,USA.
authors.forename: A N
authors.initials: AN
authors.lastname: Simmons
authors.affiliation: Department of Psychiatry,University of California San Diego,La Jolla,CA,USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Sullivan
authors.affiliation: Department of Psychiatry,University of California San Diego,La Jolla,CA,USA.
authors.forename: C B
authors.initials: CB
authors.lastname: Allard
authors.affiliation: Department of Psychiatry,University of California San Diego,La Jolla,CA,USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Paulus
authors.affiliation: Department of Psychiatry,University of California San Diego,La Jolla,CA,USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Stein
mesh_terms: D000328:Adult; D054523:Adult Survivors of Child Abuse / Q000523:psychology*; D001007:Anxiety / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D004644:Emotions; D005149:Facial Expression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D011569:Psychiatric Status Rating Scales; D013315:Stress, Psychological / Q000523:psychology*; D055815:Young Adult
keywords: Amygdala; anxiety; childhood maltreatment; early life stress; imaging