Reduced amygdala responsivity during conditioning to trauma‐related stimuli in posttraumatic stress disorder

Abstract

Exaggerated conditioned fear responses and impaired extinction along with amygdala overactivation have been observed in posttraumatic stress disorder (PTSD). These fear responses might be triggered by cues related to the trauma through higher-order conditioning, where reminders of the trauma may serve as unconditioned stimuli (US) and could maintain the fear response. We compared arousal, valence, and US expectancy ratings and BOLD brain responses using fMRI in 14 traumatized persons with PTSD and 14 without PTSD (NPTSD) and 13 matched healthy controls (HC) in a differential aversive conditioning paradigm. The US were trauma-specific pictures for the PTSD and NPTSD group and equally aversive and arousing for the HC; the conditioned stimuli (CS) were graphic displays. During conditioning, the PTSD patients compared to the NPTSD and HC indicated higher arousal to the conditioned stimulus that was paired with the trauma picture (CS+) compared to the unpaired (CS-), increased dissociation during acquisition and extinction, and failure to extinguish the CS/US-association compared to NPTSD. During early and late acquisition, the PTSD patients showed a significantly lower amygdala activation to CS+ versus CS- and a negative interaction between activation in the amygdala and dorsolateral prefrontal cortex (PFC), while NPTSD and HC displayed a negative interaction between amygdala and medial PFC. These findings suggest maladaptive anticipatory coping with trauma-related stimuli in patients with PTSD, indicated by enhanced conditioning, with related abnormal amygdala reactivity and connectivity, and delayed extinction.

Post-Traumatic Stress Disorder Chronification via Monoaminooxidase and Cortisol Metabolism

“…These data are consistent with depressed amygdala activity in PTSD-resistant subjects [26]. The mechanism of amygdala inhibition is not completely clear.…”

PAC1R Genotype to Phenotype Correlations in Autism Spectrum Disorder

“…These data together suggest that PAC1R is closely tied to amygdala function in stress and fear response pathways, which are disrupted in PTSD. Furthermore, both PTSD and ASD involve impairment of amygdala function and social related symptoms, albeit likely via distinct etiologies [American Psychiatric Association, 2013; Davis, 1992;Diener et al, 2016;Giustino & Maren, 2015;Shin, 2006]. Beyond studies of gene expression, we examined how the G to C SNP (rs2267735) may be related to ASD social symptoms and brain connectivity.…”

“…At the functional level, the CC risk genotype in the ERE sequence compromises ERα binding, inhibiting activation of PAC1R transcription and resulting in reduced gene expression [Mercer et al, ; Ressler et al, ]. As amygdala dysfunction is a hallmark feature of PTSD [Davis, ; Diener et al, ; Giustino & Maren, ; Shin, ], these findings suggest that reduced PAC1R expression is linked to a phenotype stemming from disrupted amygdala functioning. Although mutations in PAC1R have yet to be found in ASD GWAS screens, the above‐described findings nevertheless suggest that PAC1R may act as a genetic modifier in psychiatric disorders characterized by social deficits, such as ASD.…”

Neurophysiological Correlates of Collective Trauma Recall in 2009 L'Aquila Earthquake Survivors

“…Analyses of brain sources suggested a lower intensity in the survivors, mainly in the right amygdala, hippocampus, parahippocampal, and temporopolar areas. The lower intensity of limbic regions in the survivors could represent a defensive approach toward the task and its emotional involvement, suggesting the presence of a distancing strategy and dysregulated emotional processing in relation to the trauma (Diener et al., ; Dutra & Wolf, ; Hopper, Frewen, Van der Kolk, & Lanius, ). This finding is in opposition to that which was reported in a previous study, which showed a higher activation of the limbic areas in earthquake survivors (Du et al., ).…”