Stephanie N DeCross1, Kelly A Sambrook2, Margaret A Sheridan3, Nim Tottenham4, Katie A McLaughlin5. 1. Department of Psychology, Harvard University, Cambridge, Massachusetts. Electronic address: sdecross@g.harvard.edu. 2. Department of Radiology, University of Washington, Seattle, Washington. 3. Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 4. Department of Psychology, Columbia University, New York, New York. 5. Department of Psychology, Harvard University, Cambridge, Massachusetts.
Abstract
BACKGROUND: Altered aversive learning represents a potential mechanism through which childhood trauma (CT) might influence risk for psychopathology. This study examines the temporal dynamics of neural activation and patterns of functional connectivity during aversive learning in children with and without exposure to CT involving interpersonal violence and evaluates whether these neural patterns mediate the association of CT with psychopathology in a longitudinal design. METHODS: A total of 147 children (aged 8-16 years, 77 with CT) completed a fear conditioning procedure during a functional magnetic resonance imaging scan. Dynamic patterns of neural activation were examined, and functional connectivity was assessed with generalized psychophysiological interaction analyses. We evaluated whether the associations between CT and psychopathology symptoms at baseline and 2-year follow-up were mediated by neural activation and connectivity during aversive learning. RESULTS: Children exposed to trauma displayed blunted patterns of neural activation over time to the conditioned threat versus safety stimuli (CS+>CS-) in the right amygdala. In addition, trauma was associated with reduced functional connectivity of right amygdala with the hippocampus, posterior parahippocampal gyrus, and posterior cingulate cortex and with elevated connectivity with the anterior cingulate cortex to CS+>CS-. The longitudinal association between CT and later externalizing symptoms was mediated by blunted activation in the right amygdala. Reduced amygdala-hippocampal connectivity mediated the association of CT with transdiagnostic anxiety symptoms, and elevated amygdala-anterior cingulate cortex connectivity mediated the association of CT with generalized anxiety symptoms. CONCLUSIONS: CT is associated with poor threat-safety discrimination and altered functional coupling between salience and default mode network regions during aversive learning. These altered dynamics may be key mechanisms linking CT with distinct forms of psychopathology.
BACKGROUND: Altered aversive learning represents a potential mechanism through which childhood trauma (CT) might influence risk for psychopathology. This study examines the temporal dynamics of neural activation and patterns of functional connectivity during aversive learning in children with and without exposure to CT involving interpersonal violence and evaluates whether these neural patterns mediate the association of CT with psychopathology in a longitudinal design. METHODS: A total of 147 children (aged 8-16 years, 77 with CT) completed a fear conditioning procedure during a functional magnetic resonance imaging scan. Dynamic patterns of neural activation were examined, and functional connectivity was assessed with generalized psychophysiological interaction analyses. We evaluated whether the associations between CT and psychopathology symptoms at baseline and 2-year follow-up were mediated by neural activation and connectivity during aversive learning. RESULTS: Children exposed to trauma displayed blunted patterns of neural activation over time to the conditioned threat versus safety stimuli (CS+>CS-) in the right amygdala. In addition, trauma was associated with reduced functional connectivity of right amygdala with the hippocampus, posterior parahippocampal gyrus, and posterior cingulate cortex and with elevated connectivity with the anterior cingulate cortex to CS+>CS-. The longitudinal association between CT and later externalizing symptoms was mediated by blunted activation in the right amygdala. Reduced amygdala-hippocampal connectivity mediated the association of CT with transdiagnostic anxiety symptoms, and elevated amygdala-anterior cingulate cortex connectivity mediated the association of CT with generalized anxiety symptoms. CONCLUSIONS: CT is associated with poor threat-safety discrimination and altered functional coupling between salience and default mode network regions during aversive learning. These altered dynamics may be key mechanisms linking CT with distinct forms of psychopathology.
Authors: B Birmaher; S Khetarpal; D Brent; M Cully; L Balach; J Kaufman; S M Neer Journal: J Am Acad Child Adolesc Psychiatry Date: 1997-04 Impact factor: 8.829
Authors: Katie A McLaughlin; Jennifer Greif Green; Michael J Gruber; Nancy A Sampson; Alan M Zaslavsky; Ronald C Kessler Journal: Arch Gen Psychiatry Date: 2010-02