title: Amotivation in schizophrenia: integrated assessment with behavioral, clinical, and imaging measures.
abstract: Motivational deficits play a central role in disability caused by schizophrenia and constitute a major unmet therapeutic need. Negative symptoms have previously been linked to hypofunction in ventral striatum (VS), a core component of brain motivation circuitry. However, it remains unclear to what extent this relationship holds for specific negative symptoms such as amotivation, and this question has not been addressed with integrated behavioral, clinical, and imaging measures. Here, 41 individuals with schizophrenia and 37 controls performed a brief, computerized progressive ratio task (PRT) that quantifies effort exerted in pursuit of monetary reward. Clinical amotivation was assessed using the recently validated Clinical Assessment Interview for Negative Symptoms (CAINS). VS function was probed during functional magnetic resonance imaging using a monetary guessing paradigm. We found that individuals with schizophrenia had diminished motivation as measured by the PRT, which significantly and selectively related to clinical amotivation as measured by the CAINS. Critically, lower PRT motivation in schizophrenia was also dimensionally related to VS hypofunction. Our results demonstrate robust dimensional associations between behavioral amotivation, clinical amotivation, and VS hypofunction in schizophrenia. Integrating behavioral measures such as the PRT will facilitate translational efforts to identify biomarkers of amotivation and to assess response to novel therapeutic interventions.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA; danwolf@upenn.edu.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Wolf
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA;
authors.forename: Theodore D
authors.initials: TD
authors.lastname: Satterthwaite
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA;
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Kantrowitz
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA;
authors.forename: Natalie
authors.initials: N
authors.lastname: Katchmar
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA;
authors.forename: Lillie
authors.initials: L
authors.lastname: Vandekar
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Elliott
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA;
authors.forename: Kosha
authors.initials: K
authors.lastname: Ruparel
mesh_terms: D000328:Adult; D057565:Apathy / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009042:Motivation / Q000502:physiology*; D012201:Reward; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology*; D066328:Ventral Striatum / Q000503:physiopathology*; D055815:Young Adult
keywords: fMRI; motivation; negative symptoms; progressive ratio; ventral striatum