Josiane Bourque1, Philip A Spechler1, Stéphane Potvin1, Robert Whelan1, Tobias Banaschewski1, Arun L W Bokde1, Uli Bromberg1, Christian Büchel1, Erin Burke Quinlan1, Sylvane Desrivières1, Herta Flor1, Vincent Frouin1, Penny Gowland1, Andreas Heinz1, Bernd Ittermann1, Jean-Luc Martinot1, Marie-Laure Paillère-Martinot1, Sarah C McEwen1, Frauke Nees1, Dimitri Papadopoulos Orfanos1, Tomáš Paus1, Luise Poustka1, Michael N Smolka1, Nora C Vetter1, Henrik Walter1, Gunter Schumann1, Hugh Garavan1, Patricia J Conrod1. 1. From the Department of Psychiatry, Université de Montréal, CHU Ste.-Justine Hospital and IUSMM Research Center, Montreal; the Departments of Psychiatry and Psychology, University of Vermont, Burlington; the Department of Psychology, University College Dublin, Dublin; the Department of Child and Adolescent Psychiatry and Psychotherapy and the Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; the Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany; the Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin; the University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; the Medical Research Council-Social, Genetic and Developmental Psychiatry Centre and the Department of Psychological Medicine and Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, U.K.; Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center, Paris; the Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, Nottingham, U.K.; the Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin; the Physikalisch-Technische Bundesanstalt, Braunschweig and Berlin, Germany; the Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging and Psychiatry," University Paris Sud, University Paris Descartes-Sorbonne Paris Cité, Paris; the Maison de Solenn, Paris; the Department of Adolescent Psychopathology and Medicine, Maison de Solenn, Cochin Hospital, Paris; the Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles; the Rotman Research Institute, Baycrest, and the Departments of Psychology and Psychiatry, University of Toronto, Toronto; the Department of Child and Adolescent Psychiatry and Psychotherapy, Medical University of Vienna, Vienna; the Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
Abstract
OBJECTIVE: This study investigated the neural correlates of psychotic-like experiences in youths during tasks involving inhibitory control, reward anticipation, and emotion processing. A secondary aim was to test whether these neurofunctional correlates of risk were predictive of psychotic symptoms 2 years later. METHOD: Functional imaging responses to three paradigms-the stop-signal, monetary incentive delay, and faces tasks-were collected in youths at age 14, as part of the IMAGEN study. At baseline, youths from London and Dublin sites were assessed on psychotic-like experiences, and those reporting significant experiences were compared with matched control subjects. Significant brain activity differences between the groups were used to predict, with cross-validation, the presence of psychotic symptoms in the context of mood fluctuation at age 16, assessed in the full sample. These prediction analyses were conducted with the London-Dublin subsample (N=246) and the full sample (N=1,196). RESULTS: Relative to control subjects, youths reporting psychotic-like experiences showed increased hippocampus/amygdala activity during processing of neutral faces and reduced dorsolateral prefrontal activity during failed inhibition. The most prominent regional difference for classifying 16-year-olds with mood fluctuation and psychotic symptoms relative to the control groups (those with mood fluctuations but no psychotic symptoms and those with no mood symptoms) was hyperactivation of the hippocampus/amygdala, when controlling for baseline psychotic-like experiences and cannabis use. CONCLUSIONS: The results stress the importance of the limbic network's increased response to neutral facial stimuli as a marker of the extended psychosis phenotype. These findings might help to guide early intervention strategies for at-risk youths.
OBJECTIVE: This study investigated the neural correlates of psychotic-like experiences in youths during tasks involving inhibitory control, reward anticipation, and emotion processing. A secondary aim was to test whether these neurofunctional correlates of risk were predictive of psychotic symptoms 2 years later. METHOD: Functional imaging responses to three paradigms-the stop-signal, monetary incentive delay, and faces tasks-were collected in youths at age 14, as part of the IMAGEN study. At baseline, youths from London and Dublin sites were assessed on psychotic-like experiences, and those reporting significant experiences were compared with matched control subjects. Significant brain activity differences between the groups were used to predict, with cross-validation, the presence of psychotic symptoms in the context of mood fluctuation at age 16, assessed in the full sample. These prediction analyses were conducted with the London-Dublin subsample (N=246) and the full sample (N=1,196). RESULTS: Relative to control subjects, youths reporting psychotic-like experiences showed increased hippocampus/amygdala activity during processing of neutral faces and reduced dorsolateral prefrontal activity during failed inhibition. The most prominent regional difference for classifying 16-year-olds with mood fluctuation and psychotic symptoms relative to the control groups (those with mood fluctuations but no psychotic symptoms and those with no mood symptoms) was hyperactivation of the hippocampus/amygdala, when controlling for baseline psychotic-like experiences and cannabis use. CONCLUSIONS: The results stress the importance of the limbic network's increased response to neutral facial stimuli as a marker of the extended psychosis phenotype. These findings might help to guide early intervention strategies for at-risk youths.
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