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Published July 19, 2024 | Version v2

Reduced discrimination between signals of danger and safety but not overgeneralization is linked to exposure to childhood adversity in healthy adults

  • 1. Institute for Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 2. Department of Psychiatry, Center of Mental Health, University Hospital of Würzburg, University of Würzburg, Würzburg, Germany
  • 3. Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  • 4. Institute for Translational Psychiatry, University of Münster, Münster, Germany
  • 5. Institute for Translational Psychiatry, University of Münster, Münster, Germany; Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt – Goethe University, Frankfurt am Main, Germany
  • 6. Department of Psychiatry, Center of Mental Health, University Hospital of Würzburg, University of Würzburg, Würzburg, Germany; Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany
  • 7. Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt – Goethe University, Frankfurt am Main, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany
  • 8. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, University of Würzburg, Würzburg, Germany
  • 9. Kbo Inn Salzach Hospital Clinical Center for Psychiatry, Wasserburg am Inn, Germany, Department of Psychiatry, LMU Munich, Munich, Germany; Department of Psychiatry, Ludwig-Maximilian-University Munich, Munich, Germany
  • 10. Department of Psychology and Center of Mental Health, Julius Maximilians University of Würzburg, Würzburg, Germany
  • 11. Department of Psychology, Biological Psychology and Cognitive Neuroscience, University of Bielefeld, Bielefeld, Germany

Description

 Childhood adversity is a strong predictor for developing psychopathological conditions. Exposure to threat-related childhood adversity has been suggested to be specifically linked to altered emotional learning as well as changes in neural circuits involved in emotional responding and fear. Learning mechanisms are particularly interesting as they are central mechanisms through which environmental inputs shape emotional and cognitive processes and ultimately behavior. Multiple theories on the mechanisms underlying this association have been suggested which, however, differ in the operationalization of “exposure”. In the current study, 1,402 physically and mentally healthy participants underwent a differential fear conditioning paradigm including a fear acquisition and generalization phase while skin conductance responses (SCRs) and different subjective ratings were acquired. Childhood adversity was retrospectively assessed through the childhood trauma questionnaire (CTQ) and participants were classified as individuals exposed or unexposed to at least moderate childhood adversity according to established cut-off criteria. In addition, we provide exploratory analyses aiming to translate different (verbal) theories on how exposure to childhood adversity is related to learning from threat into statistical models. During fear acquisition training and generalization, childhood adversity was related to reduced discrimination in SCRs between stimuli signaling danger vs. safety, primarily due to reduced responding to danger cues. During fear generalization, no differences in the degree of generalization were observed between exposed and unexposed individuals but generally blunted SCRs occurred in exposed individuals. No differences between the groups were observed in ratings in any of the experimental phases. The reduced discrimination between signals of danger and safety in SCRs in exposed individuals was evident across different operationalizations of “exposure” which was guided by different (verbal) theories. Of note, none of these tested theories showed clear explanatory superiority. Our results stand in stark contrast to typical patterns observed in patients suffering from anxiety and stress-related disorders (i.e., reduced discrimination between danger and safety cues due to increased responses to safety signals). However, reduced CS discrimination - albeit due to blunted CS+ responses - is also observed in patient or at risk samples reporting childhood adversity, suggesting that this pattern may be specific to individuals with a history of childhood adversity. In addition, we conclude that theories linking childhood adversity to psychopathology need refinement.

Notes

The zip-folder contains the code, text, and tables necessary to create the manuscript with the above title that is currently being submitted. The data were not published alongside, as open access to the data was not indicated in the ethical approval. The manuscript is currently under revision at eLife. The current preprint can be found here: https://doi.org/10.1101/2023.09.26.559474. This work was supported by the German Research Foundation (DFG) – project number 44541416 – TRR 58 "Fear, Anxiety, Anxiety Disorders", subproject Z02 to JD, KD, UD, TBL, UL, AR, MR, PP; subproject B01 to PP, subproject B07 to TBL, subproject C02 to KD and JD, subproject C10 to MG. 

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