| Abstract |
Investigated underlying mechanisms of heightened emotional reactivity in posttraumatic stress disorder (PTSD). Moreover, an experimental approach aiming at attenuating a newly formed aversive emotional memory was tested, to provide further insights into processes that may contribute to overcome strong negative emotional states. In the first study, alterations in the acquisition and generalization of fear were examined. A recently introduced fear conditioning and generalization paradigm was studied in 30 PTSD individuals, 30 healthy trauma-exposed and 30 trauma-unexposed healthy control participants. The paradigm covers a range of stimuli parametrically varying in their similarity and thus, forming a continuum between the danger and safety cue. This allows the testing of fear transfer to stimuli that resemble the danger cue. Hints towards altered emotional reactivity, here, alterations in generalization were found with respect to reaction times while evaluating the risk of an aversive event associated with generalization stimuli in PTSD: PTSD patients were slower in judging the risk related to stimuli of moderate similarity to the danger cue. Additionally, PTSD subjects overall subjectively expected more risk irrespective of the stimulus type across all experimental phases. Importantly, while explicit risk perception was linked to PTSD, implicit measures of overgeneralization were related to traumatization per se. In a second study, neurophysiological underpinnings of emotion regulation have been addressed. Specifically, the combination of heart rate variability (HRV) and its neuronal response pattern (central autonomic network, CAN) was assessed in 57 PTSD individuals and 41 healthy control subjects during resting state functional magnetic resonance imaging (fMRI). PTSD patients were characterized by lower HRV compared to controls. Moreover, PTSD subjects exhibited a widespread connectivity pattern between key nodes of the CAN and multiple cortical and subcortical areas compared to controls. Importantly, while CAN connectivity was related to HRV in controls, this association was not found to be significant in PTSD. These data were interpreted in the frame of increased emotional reactivity and a decoupling of central and autonomic functioning in PTSD. In a third study, we investigated whether pharmacological and behavioral interventions applied during memory reconsolidation can attenuate a prior acquired fear memory. A differential fear conditioning paradigm was studied in 80 female healthy individuals: Two stimuli (CS+) were associated with an aversive event, while one (CS-) was never followed by an aversive event. Pharmacological (propranolol) and behavioral (reappraisal, multimodal sensory stimulation) intervention protocols were applied upon memory reactivation of one of the two CS+ (reconsolidation disruption) and contrasted to a placebo control condition. Effects on memory were tested during extinction and reinstatement testing. Differential effects regarding the reactivated and nonreactivated CS+ have only been observed in the propranolol condition. Specifically, fear memory was stronger in response to the nonreactivated CS+ compared to the placebo group. None of the behavioral interventions attenuated fear memory. The findings are discussed with respect to boundary conditions. In sum, the studies extended prior investigations on emotional reactivity in PTSD, indicating altered emotional reactivity to safe stimuli resembling the danger cue. Together with increased subjective risk perception and alterations in baseline responding and fear learning, these findings provide further evidence for a correlate of altered emotional reactivity in PTSD. There was evidence of a psychophysiological-neuronal profile contributing to emotion regulation difficulties in PTSD. The results implicate the importance of emotional (over-) reactivity in PTSD in contributing to the defined symptom pattern of PTSD. However, an attempt to experimentally target emotional memories did not show a beneficial effect by combining reconsolidation with either a pharmacological agent (propranolol) or behavioral therapeutic techniques on a prior established fear memory. Possible implications for PTSD psychotherapy include strategies that reduce uncertainty in safe situations. - Contents: (1) Thome, J., Hauschild, S., Liebke, L., Rausch, S., Herzog, J.I., Müller-Engelmann, M., Steil, R., Priebe, K., Hermans, D., Schmahl, C., Bohus, M. & Lis, S. (n. d.). Generalization of fear in PTSD related to prolonged childhood maltreatment: An experimental study. Manuscript submitted for publication. (2) Thome, J., Densmore, M., Frewen, P.A., McKinnon, M.C., Theberge, J., Nicholson, A.A. & Lanius, R.A. (2017). Desynchronization of autonomic response and central autonomic network connectivity in posttraumatic stress disorder. Human Brain Mapping, 38, 27-40. DOI: 10.1002/hbm.23340. (3) Thome, J., Koppe, G., Hauschild, S., Liebke, L., Schmahl, C., Lis, S. & Bohus, M. (2016). Modification of fear memory by pharmacological and behavioural interventions during reconsolidation. PLoS One, 11:e0161044. DOI: 10.1371/journal.pone.0161044.
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