title: Symptom dimensions are associated with reward processing in unmedicated persons at risk for psychosis.
abstract: There is growing evidence that reward processing is disturbed in schizophrenia. However, it is uncertain whether this dysfunction predates or is secondary to the onset of psychosis. Studying 21 unmedicated persons at risk for psychosis plus 24 healthy controls (HCs) we used a incentive delay paradigm with monetary rewards during functional magnetic resonance imaging. During processing of reward information, at-risk individuals performed similarly well to controls and recruited the same brain areas. However, while anticipating rewards, the high-risk sample exhibited additional activation in the posterior cingulate cortex, and the medio- and superior frontal gyrus, whereas no significant group differences were found after rewards were administered. Importantly, symptom dimensions were differentially associated with anticipation and outcome of the reward. Positive symptoms were correlated with the anticipation signal in the ventral striatum (VS) and the right anterior insula (rAI). Negative symptoms were inversely linked to outcome-related signal within the VS, and depressive symptoms to outcome-related signal within the medial orbitofrontal cortex (mOFC). Our findings provide evidence for a reward-associated dysregulation that can be compensated by recruitment of additional prefrontal areas. We propose that stronger activations within VS and rAI when anticipating a reward reflect abnormal processing of potential future rewards. Moreover, according to the aberrant salience theory of psychosis, this may predispose a person to positive symptoms. Additionally, we report evidence that negative and depressive symptoms are differentially associated with the receipt of a reward, which might demonstrate a broader vulnerability to motivational and affective symptoms in persons at-risk for psychosis.
authors.affiliation: University Hospital of Psychiatry Zurich, the Zurich Program for Sustainable Development of Mental Health Services (ZInEP) Zurich, Switzerland ; Department of Neuroradiology, University Hospital of Zurich Zurich, Switzerland ; Collegium Helveticum, A Joint Research Institute between the University of Zurich and the Swiss Federal Institute of Technology Zurich Zurich, Switzerland.
authors.forename: Diana
authors.initials: D
authors.lastname: Wotruba
authors.affiliation: University Hospital of Psychiatry Zurich, the Zurich Program for Sustainable Development of Mental Health Services (ZInEP) Zurich, Switzerland ; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Switzerland.
authors.forename: Karsten
authors.initials: K
authors.lastname: Heekeren
authors.affiliation: Department of Neuroradiology, University Hospital of Zurich Zurich, Switzerland ; Center for MR Research, University Children's Hospital Zurich Zurich, Switzerland.
authors.forename: Lars
authors.initials: L
authors.lastname: Michels
authors.affiliation: University Hospital of Psychiatry Zurich, the Zurich Program for Sustainable Development of Mental Health Services (ZInEP) Zurich, Switzerland ; Department of Neuroradiology, University Hospital of Zurich Zurich, Switzerland.
authors.forename: Roman
authors.initials: R
authors.lastname: Buechler
authors.affiliation: Department of General Internal Medicine and Psychosomatics, Centre for Psychosocial Medicine, University Hospital Heidelberg Heidelberg, Germany.
authors.forename: Joe J
authors.initials: JJ
authors.lastname: Simon
authors.affiliation: University Hospital of Psychiatry Zurich, the Zurich Program for Sustainable Development of Mental Health Services (ZInEP) Zurich, Switzerland ; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Switzerland.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Theodoridou
authors.affiliation: Department of Neuroradiology, University Hospital of Zurich Zurich, Switzerland.
authors.forename: Spyros
authors.initials: S
authors.lastname: Kollias
authors.affiliation: University Hospital of Psychiatry Zurich, the Zurich Program for Sustainable Development of Mental Health Services (ZInEP) Zurich, Switzerland ; Collegium Helveticum, A Joint Research Institute between the University of Zurich and the Swiss Federal Institute of Technology Zurich Zurich, Switzerland ; Laboratory of Neuroscience (LIM-27), Institute of Psychiatry, University of Sao Paulo Sao Paulo, Brazil.
authors.forename: Wulf
authors.initials: W
authors.lastname: Rössler
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Switzerland ; Center for Integrative Human Physiology, University of Zurich Zurich, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kaiser
keywords: anterior insula; at-risk mental state; dopamine; functional magnetic resonance imaging (fMRI); psychosis; reward; salience processing; ventral striatum