title: Early-Life Stress Affects Stress-Related Prefrontal Dopamine Activity in Healthy Adults, but Not in Individuals with Psychotic Disorder.
abstract: Early life stress may have a lasting impact on the developmental programming of the dopamine (DA) system implicated in psychosis. Early adversity could promote resilience by calibrating the prefrontal stress-regulatory dopaminergic neurotransmission to improve the individual's fit with the predicted stressful environment. Aberrant reactivity to such match between proximal and distal environments may, however, enhance psychosis disease risk. We explored the combined effects of childhood adversity and adult stress by exposing 12 unmedicated individuals with a diagnosis of non-affective psychotic disorder (NAPD) and 12 healthy controls (HC) to psychosocial stress during an [18F]fallypride positron emission tomography. Childhood trauma divided into early (ages 0-11 years) and late (12-18 years) was assessed retrospectively using a questionnaire. A significant group x childhood trauma interaction on the spatial extent of stress-related [18F]fallypride displacement was observed in the mPFC for early (b = -8.45, t(1,23) = -3.35, p = .004) and late childhood trauma (b = -7.86, t(1,23) = -2.48, p = .023). In healthy individuals, the spatial extent of mPFC DA activity under acute psychosocial stress was positively associated with the severity of early (b = 7.23, t(11) = 3.06, p = .016) as well as late childhood trauma (b = -7.86, t(1,23) = -2.48, p = .023). Additionally, a trend-level main effect of early childhood trauma on subjective stress response emerged within this group (b = -.7, t(11) = -2, p = .07), where higher early trauma correlated with lower subjective stress response to the task. In the NAPD group, childhood trauma was not associated with the spatial extent of the tracer displacement in mPFC (b = -1.22, t(11) = -0.67), nor was there a main effect of trauma on the subjective perception of stress within this group (b = .004, t(11) = .01, p = .99). These findings reveal a potential mechanism of neuroadaptation of prefrontal DA transmission to early life stress and suggest its role in resilience and vulnerability to psychosis.
authors.affiliation: Department of Neuroscience, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Kasanova
authors.affiliation: Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands.
authors.forename: Dennis
authors.initials: D
authors.lastname: Hernaus
authors.affiliation: Department of Neuroscience, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vaessen
authors.affiliation: Department of Neuroscience, KU Leuven-University of Leuven, Leuven, Belgium.|Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Thérèse
authors.initials: T
authors.lastname: van Amelsvoort
authors.affiliation: Department of Nuclear Medicine, University Hospital RWTH Aachen University, Aachen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Winz
authors.affiliation: Department of Nuclear Medicine, University Hospital RWTH Aachen University, Aachen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Heinzel
authors.affiliation: Department of Psychiatry, Douglas Mental Health Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Jens
authors.initials: J
authors.lastname: Pruessner
authors.affiliation: Department of Nuclear Medicine, University Hospital RWTH Aachen University, Aachen, Germany.|Department of Nuclear Medicine, Maastricht University Hospital, Maastricht, The Netherlands.
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.affiliation: Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands.
authors.forename: Dina
authors.initials: D
authors.lastname: Collip
authors.affiliation: Department of Neuroscience, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Inez
authors.initials: I
authors.lastname: Myin-Germeys
mesh_terms: D000293:Adolescent; D000328:Adult; D001549:Benzamides / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004298:Dopamine / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017397:Prefrontal Cortex / Q000378:metabolism*; D011618:Psychotic Disorders / Q000378:metabolism*; D013315:Stress, Psychological
chemical_list: D001549:Benzamides; D005462:Fluorine Radioisotopes; C574003:fallypride; D004298:Dopamine