title: Ventral striatal hypoactivation is associated with apathy but not diminished expression in patients with schizophrenia.
abstract: Negative symptoms of schizophrenia can be grouped in 2 dimensions: apathy and diminished expression. Increasing evidence suggests that negative symptoms are associated with altered neural activity of subcortical and cortical regions in the brain reward system. However, the neurobiological basis of the distinct symptom dimensions within negative symptoms is still poorly understood. The primary aim of our study was to examine the neural correlates of the negative symptom dimensions apathy and diminished expression during a reward processing task.
  
  
  
  Patients with schizophrenia and healthy controls underwent event-related fMRI while performing a variant of the Monetary Incentive Delay Task. We assessed negative symptom dimensions using the Brief Negative Symptom Scale.
  
  
  
  We included 27 patients and 25 controls in our study. Both groups showed neural activation indicated by blood oxygen-level dependent signal in the ventral striatum during reward anticipation. Ventral striatal activation during reward anticipation showed a strong negative correlation with apathy. Importantly, this effect was not driven by cognitive ability, medication, depressive or positive symptoms. In contrast, no significant correlation with the diminished expression dimension was observed.
  
  
  
  Although the results remain significant when controlling for chlorpromazine equivalents, we cannot fully exclude potential confounding effects of medication with atypical antipsychotics.
  
  
  
  The specific correlation of ventral striatal hypoactivation during reward anticipation with apathy demonstrates a differentiation of apathy and diminished expression on a neurobiological level and provides strong evidence for different pathophysiological mechanisms underlying these 2 negative symptom dimensions. Our findings contribute to a multilevel framework in which apathy and motivational impairment in patients with schizophrenia can be described on psychopathological, behavioural and neural levels.
authors.affiliation: From the Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, (Kirschner, Hager, Bischof, Hartmann, Kluge, Seifritz, Kaiser); and the Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich (Hager, Hartmann, Tobler), Zurich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kirschner
authors.affiliation: From the Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, (Kirschner, Hager, Bischof, Hartmann, Kluge, Seifritz, Kaiser); and the Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich (Hager, Hartmann, Tobler), Zurich, Switzerland.
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Hager
authors.affiliation: From the Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, (Kirschner, Hager, Bischof, Hartmann, Kluge, Seifritz, Kaiser); and the Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich (Hager, Hartmann, Tobler), Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Bischof
authors.affiliation: From the Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, (Kirschner, Hager, Bischof, Hartmann, Kluge, Seifritz, Kaiser); and the Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich (Hager, Hartmann, Tobler), Zurich, Switzerland.
authors.forename: Matthias N
authors.initials: MN
authors.lastname: Hartmann
authors.affiliation: From the Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, (Kirschner, Hager, Bischof, Hartmann, Kluge, Seifritz, Kaiser); and the Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich (Hager, Hartmann, Tobler), Zurich, Switzerland.
authors.forename: Agne
authors.initials: A
authors.lastname: Kluge
authors.affiliation: From the Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, (Kirschner, Hager, Bischof, Hartmann, Kluge, Seifritz, Kaiser); and the Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich (Hager, Hartmann, Tobler), Zurich, Switzerland.
authors.forename: Erich
authors.initials: E
authors.lastname: Seifritz
authors.affiliation: From the Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, (Kirschner, Hager, Bischof, Hartmann, Kluge, Seifritz, Kaiser); and the Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich (Hager, Hartmann, Tobler), Zurich, Switzerland.
authors.forename: Philippe N
authors.initials: PN
authors.lastname: Tobler
authors.affiliation: From the Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, (Kirschner, Hager, Bischof, Hartmann, Kluge, Seifritz, Kaiser); and the Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich (Hager, Hartmann, Tobler), Zurich, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kaiser
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D057565:Apathy / Q000502:physiology*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D012201:Reward; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy; D012565:Schizophrenic Psychology; D066328:Ventral Striatum / Q000000981:diagnostic imaging / Q000503:physiopathology*
chemical_list: D014150:Antipsychotic Agents; D010100:Oxygen