Background: A clinical characteristic of posttraumatic stress disorder (PTSD) is persistently elevated fear responses to stimuli associated with the traumatic event. The objective herein is to determine whether extinction of fear responses is impaired in PTSD and whether such impairment is related to dysfunctional activation of brain regions known to be involved in fear extinction, viz., amygdala, hippocampus, ventromedial prefrontal cortex (vmPFC), and dorsal anterior cingulate cortex (dACC). Methods: Sixteen individuals diagnosed with PTSD and 15 trauma-exposed non-PTSD controls (TENCs) underwent a two-day fear conditioning and extinction protocol in a 3T fMRI scanner. Conditioning and extinction training were conducted on day 1. Extinction recall (or extinction memory) test was conducted on day 2 (extinguished conditioned stimuli presented in the absence of shock). Skin conductance response (SCR) was scored throughout the experiment as an index of the conditioned response. Results: SCR data revealed no significant differences between groups during acquisition and extinction of conditioned fear on day 1. On day 2, however, PTSD subjects showed impaired recall of extinction memory. Analysis of fMRI data showed greater amygdala activation in the PTSD group during day 1 extinction learning. During extinction recall, lesser activation in hippocampus and vmPFC, and greater activation in dACC, was observed in the PTSD group. The magnitude of extinction memory across all subjects was correlated with activation of hippocampus and vmPFC during extinction recall testing. Conclusions: These findings support the hypothesis that fear extinction is impaired in PTSD. They further suggest that dysfunctional activation in brain structures that mediate fear extinction learning, and especially its recall, underlie this impairment.

OBJECTIVE The strong associations between child maltreatment and psychopathology have generated interest in identifying neurodevelopmental processes that are disrupted following maltreatment. Previous research has largely focused on neural response to negative facial emotion. We determined whether child maltreatment was associated with neural responses during passive viewing of negative and positive emotional stimuli and effortful attempts to regulate emotional responses. METHOD 42 adolescents aged 13–19 years, half with exposure to physical and/or sexual abuse, participated. Blood oxygen level-dependent (BOLD) response was measured during passive viewing of negative and positive emotional stimuli and attempts to modulate emotional responses using cognitive reappraisal. RESULTS Maltreated adolescents exhibited heightened response in multiple nodes of the salience network, including amygdala, putamen, and anterior insula, to negative relative to neutral stimuli. During attempts to decrease responses to negative stimuli relative to passive viewing, maltreatment was associated with greater recruitment of superior frontal gyrus, dorsal anterior cingulate cortex, and frontal pole; adolescents with and without maltreatment down-regulated amygdala response to a similar degree. No associations were observed between maltreatment and neural response to positive emotional stimuli during passive viewing or effortful regulation. CONCLUSION Child maltreatment heightens the salience of negative emotional stimuli. Although maltreated adolescents modulate amygdala responses to negative cues to a similar degree as non-maltreated youths, they utilize regions involved in effortful control to a greater degree to do so, potentially because greater effort is required to modulate heightened amygdala responses. These findings are promising, given the centrality of cognitive restructuring in trauma-focused treatments for children.

Alterations in learning processes and the neural circuitry that supports fear conditioning and extinction represent mechanisms through which trauma exposure might influence risk for psychopathology. Few studies examine how trauma or neural structure relates to fear conditioning in children. Children (n=94) aged 6-18 years, 40.4% (n=38) with exposure to maltreatment (physical abuse, sexual abuse, or domestic violence), completed a fear conditioning paradigm utilizing blue and yellow bells as conditioned stimuli (CS+/CS-) and an aversive alarm noise as the unconditioned stimulus. Skin conductance responses (SCR) and self-reported fear were acquired. Magnetic resonance imaging data were acquired from 60 children. Children without maltreatment exposure exhibited strong differential conditioning to the CS+ vs CS-, based on SCR and self-reported fear. In contrast, maltreated children exhibited blunted SCR to the CS+ and failed to exhibit differential SCR to the CS+ vs CS- during early conditioning. Amygdala and hippocampal volume were reduced among children with maltreatment exposure and were negatively associated with SCR to the CS+ during early conditioning in the total sample, although these associations were negative only among non-maltreated children and were positive among maltreated children. The association of maltreatment with externalizing psychopathology was mediated by this perturbed pattern of fear conditioning. Child maltreatment is associated with failure to discriminate between threat and safety cues during fear conditioning in children. Poor threat-safety discrimination might reflect either enhanced fear generalization or a deficit in associative learning, which may in turn represent a central mechanism underlying the development of maltreatment-related externalizing psychopathology in children.

Context Smaller hippocampal volumes are well established in posttraumatic stress disorder (PTSD), but the relatively few studies of amygdala volume in PTSD have produced equivocal results. Objective To assess a large cohort of recent military veterans, with PTSD and trauma-exposed controls, with sufficient power to definitively assess the effect of PTSD on volumetric changes in the amygdala and hippocampus, as well as the contribution of illness duration, trauma load, and depressive symptoms. Design Case-controlled design with structural MRI and clinical diagnostic assessments. Important potential confounds of alcohol use, depression, and medication use were statistically controlled. Setting Durham VA Medical Center located in central North Carolina (USA) in proximity to major military bases. Patients Ambulatory patients (n=200), recruited from a registry of military service members and veterans serving after 11-September 2001, consisting of a group with current PTSD (n=99) and trauma-exposed comparison group without PTSD (n=101). Main Outcome measure Amygdala and hippocampus volumes computed from automated segmentation of high-resolution structural MRI acquired at 3 Tesla. Results Smaller volume was demonstrated in the PTSD compared to non-PTSD groups for the left amygdala (p = .002), right amygdala (p = .01), and left hippocampus (p = .02), but not for the right hippocampus (p = .25). Amygdala volumes were not associated with PTSD chronicity, trauma load, or severity of depressive symptoms. Conclusions These results provide clear evidence of an association between smaller amygdala volume and PTSD. The lack of correlation between trauma load or illness chronicity and amygdala volume suggests that either a smaller amygdala represents a vulnerability to developing PTSD, or the lack of a dose-response relationship with amygdala volume. Our results may trigger a renewed impetus for investigating structural differences in the amygdala, its genetic determinants, its environmental modulators, and the possibility that it reflects an intrinsic vulnerability to PTSD.