title: Striatal Reward Activity and Antipsychotic-Associated Weight Change in Patients With Schizophrenia Undergoing Initial Treatment.
abstract: OBJECTIVE
  Weight gain is a common and serious adverse effect of antipsychotic treatment. A variable individual predisposition to development of metabolic disturbances calls for predictive biological markers.
  
  
  OBJECTIVE
  To investigate whether attenuated striatal activity during reward anticipation is associated with amisulpride-induced weight change in antipsychotic-naive patients with schizophrenia undergoing initial treatment and to examine the association between weight change and changes in reward anticipation activity after treatment.
  
  
  METHODS
  Sixty-nine antipsychotic-naive inpatients and outpatients with schizophrenia were included in a multimodal longitudinal cohort study from December 16, 2008, to December 11, 2013. Fifty-eight patients underwent functional magnetic resonance imaging (fMRI) while performing a monetary reward task. After 6 weeks of treatment with amisulpride, a relatively selective dopamine D2 antagonist, 39 patients underwent a second fMRI scan and measurement of change in body weight. Final follow-up was completed on January 14, 2014, and data were analyzed from October 25, 2014, to June 15, 2015 and August 31 to September 19, 2015.
  
  
  METHODS
  Six weeks of individually dosed amisulpride treatment.
  
  
  METHODS
  Reward-anticipation activity in the striatum before and after treatment and weight change.
  
  
  RESULTS
  Of the 69 patients who consented to the study, 39 underwent the follow-up fMRI and weight measurement (age range, 18-45 years; 17 women and 22 men). The mean (SD) daily dose of amisulpride was 272 (168; range, 50-800) mg, and patients gained a mean (SD) of 2.3 (2.8; range, -4 to 8) kg in body weight. Improvement from baseline to follow-up was found on the mean (SD) positive (19.9 [4.1] to 14.3 [3.8]), general (39.7 [7.7] to 30.5 [7.7]), and total (78.5 [15.3] to 63.2 [13.9]) scores on the Positive and Negative Syndrome Scale (P < .001). Weight gain was predicted by low mean (SD) baseline reward-related activity in the right-sided putamen (0.20 [0.93]; F35,3 = 5.64; P = .003). After 6 weeks, weight gain was associated with an increase in mean (SD) reward activity in the same region during treatment (0.28 [0.74]; F37,1 = 4.48; P = .04).
  
  
  CONCLUSIONS
  Activity in striatal regions of the reward system appears to be associated with the individual variability in the predisposition for antipsychotic-associated weight gain. Moreover, pharmacologic modulation of the reward system may play a role in antipsychotic-associated weight gain.
authors.affiliation: Centre for Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Copenhagen, Denmark2Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Cop.
authors.forename: Mette Ø
authors.initials: MØ
authors.lastname: Nielsen
authors.affiliation: Functional Imaging Unit, Department of Clinical Physiology and Nuclear Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Egill
authors.initials: E
authors.lastname: Rostrup
authors.affiliation: Centre for Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Copenhagen, Denmark2Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Cop.
authors.forename: Sanne
authors.initials: S
authors.lastname: Wulff
authors.affiliation: Centre for Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Copenhagen, Denmark2Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Cop.
authors.forename: Birte
authors.initials: B
authors.lastname: Glenthøj
authors.affiliation: Centre for Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Copenhagen, Denmark2Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Cop.
authors.forename: Bjørn H
authors.initials: BH
authors.lastname: Ebdrup
mesh_terms: D000293:Adolescent; D000328:Adult; D000077582:Amisulpride; D059031:Anticipation, Psychological / Q000187:drug effects; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011699:Putamen / Q000187:drug effects* / Q000503:physiopathology; D012201:Reward; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D013469:Sulpiride / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D013469:Sulpiride; D000077582:Amisulpride