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Psychol Med. 2012 Feb;42(2):283-94. doi: 10.1017/S0033291711001474. Epub 2011 Aug 11.

Evidence that genes for depression impact on the pathway from trauma to psychotic-like symptoms by occasioning emotional dysregulation.

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GGz Eindhoven en de Kempen, Eindhoven, The Netherlands.
Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, European Graduate School of Neuroscience, Maastricht, The Netherlands.
Department of Human Genetics, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Belgium.
Association for Scientific Research in Multiple Births, Ghent, Belgium.



Genes for depression may act by making individuals more sensitive to childhood trauma. Given that childhood adversity is a risk factor for adult psychosis and symptoms of depression and psychosis tend to cluster within individuals and families, the aim was to examine whether the association between childhood adversity and psychotic-like symptoms is moderated by genetic liability for depression. A secondary aim was to determine to what degree a depression-related increase in stress sensitivity or depressive symptoms themselves occasioned the moderating effect.


Female twins (n=508) completed both prospective and retrospective questionnaires regarding childhood adversity [the Symptom Checklist-90 - Revised (SCL-90-R) and SCID-I (psychotic symptoms)] and psychotic trait liability [the Community Assessment of Psychic Experiences (CAPE)]. Stress sensitivity was indexed by appraisals of event-related stress and negative affect (NA) in the flow of daily life, assessed with momentary assessment technology for five consecutive days. Multilevel regression analyses were used to examine moderation of childhood adversity by genetic liability for depression in the prediction of follow-up psychotic experiences.


The effect of childhood adversity was significantly moderated by genetic vulnerability for depression in the model of both follow-up psychotic experiences (SCL-90-R) and follow-up psychotic trait liability (CAPE). The moderation by genetic liability was mediated by depressive experience but not by stress sensitivity.


Genetic liability for depression may potentiate the pathway from childhood adversity to psychotic-like symptoms through dysfunctional emotional processing of anomalous experiences associated with childhood trauma.

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