Neurobehavioural mechanisms of threat generalization moderate the link between childhood maltreatment and psychopathology in emerging adulthood

Neurobehavioural mechanisms of threat generalization moderate the link between childhood maltreatment and psychopathology in emerging adulthood

J Psychiatry Neurosci 2019;44(3):185-194 | PDF | Appendix

Iris Lange, PhD; Liesbet Goossens, PhD; Jindra Bakker, PhD; Stijn Michielse, PhD; Ruud van Winkel, MD, PhD; Shmuel Lissek, PhD; Nicole Leibold, PhD; Machteld Marcelis, MD, PhD; Marieke Wichers, PhD; Jim van Os, MD, PhD; Therese van Amelsvoort, MD, PhD; Koen Schruers, MD, PhD


Background: Childhood maltreatment is a transdiagnostic risk factor for later psychopathology and has been associated with altered brain circuitry involved in the processing of threat and safety. Examining threat generalization mechanisms in young adults with childhood maltreatment and psychiatric symptoms may elucidate a pathway linking early-life adversities to the presence of subclinical psychopathology.

Methods: We recruited youth aged 16–25 years with subclinical psychiatric symptomatology and healthy controls. They were dichotomized into 2 groups: 1 with a high level of childhood maltreatment (n = 58) and 1 with no or a low level of childhood maltreatment (n = 55). Participants underwent a functional MRI threat generalization paradigm, measuring self-reported fear, expectancy of an unconditioned stimulus (US) and neural responses.

Results: We observed interactions between childhood maltreatment and threat generalization indices on subclinical symptom load. In individuals reporting high levels of childhood maltreatment, enhanced generalization in self-reported fear and US expectancy was related to higher levels of psychopathology. Imaging results revealed that in the group with high levels of childhood maltreatment, lower activation in the left hippocampus during threat generalization was associated with a higher symptom load. Associations between threat generalization and psychopathology were nonsignificant overall in the group with no or low levels of childhood maltreatment.

Limitations: The data were acquired in a cross-sectional manner, precluding definitive insight into the causality of childhood maltreatment, threat generalization and psychopathology.

Conclusion: Our results suggest that threat generalization mechanisms may moderate the link between childhood maltreatment and subclinical psychopathology during emerging adulthood. Threat generalization could represent a vulnerability factor for developing later psychopathology in individuals being exposed to childhood maltreatment.

Submitted Apr. 4, 2018; Revised July 5, 2018; Accepted Aug. 6, 2018; Published online Dec. 13

Acknowledgements: This study was funded by a research grant from Stichting the Weijerhorst and by a fellowship of the Dutch Brain Foundation to M. Wichers (Hersenstichting Nederland: 20121-03).

Affiliations: From the Department of Psychiatry and Psychology, School of Mental Health and Neuroscience, EURON, Maastricht University, Maastricht, The Netherlands (Lange, Goossens, Bakker, Michielse, Leibold, Marcelis, van Os, van Amelsvoort, Schruers); Department of Neuroscience, Center for Contextual Psychiatry, Center for Clinical Psychiatry, KU Leuven, Leuven, Belgium (van Winkel); Department of Psychology, University of Minnesota, Minneapolis, MN, USA (Lissek); Institute for Mental Health Care Eindhoven (GGzE), Eindhoven, The Netherlands (Marcelis); Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, The Netherlands (Wichers); Department of Psychosis Studies, Institute of Psychiatry, King’s College London, King’s Health Partners, London, UK (van Os); Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands (van Os); Faculty of Psychology, Center for Experimental and Learning Psychology, KU Leuven, Leuven, Belgium (Schruers).

Competing interests: R. van Winkel reports personal fees from Johnson & Johnson, outside the submitted work. No other authors declared competing interests.

Contributors: I. Lange, L. Goossens, M. Marcelis, M. Wichers, J. van Os, T. van Amelsvoort and K. Schruers designed the study. I. Lange, J. Bakker and S. Michielse collected the data. I. Lange, L. Goossens, R. van Winkel, S. Lissek, N. Leibold and K. Schruers analyzed the data. I. Lange wrote the article, which all authors critically reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

DOI: 10.1503/jpn.180053

Correspondence to: Iris Lange, Maastricht University Medical Center, Department of Psychiatry and Psychology, P.O. Box 616 (vijv1), 6200 MD Maastricht, the Netherlands;