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@ARTICLE{Umbricht:893885,
      author       = {Umbricht, Daniel and Abt, Markus and Tamburri, Paul and
                      Chatham, Christopher and Holiga, Štefan and Frank, Michael
                      J. and Collins, Anne G. E. and Walling, David P. and Mofsen,
                      Rick and Gruener, Daniel and Gertsik, Lev and Sevigny, Jeff
                      and Keswani, Sanjay and Dukart, Juergen},
      title        = {{P}roof-of-{M}echanism {S}tudy of the {P}hosphodiesterase
                      10 {I}nhibitor {RG}7203 in {P}atients {W}ith {S}chizophrenia
                      and {N}egative {S}ymptoms},
      journal      = {Biological psychiatry},
      volume       = {1},
      number       = {1},
      issn         = {0006-3223},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {FZJ-2021-02897},
      pages        = {70 - 77},
      year         = {2021},
      abstract     = {BACKGROUND:Reduced activation of dopamine D1receptor
                      signaling may be implicated in reward functioning as
                      apotential driver of negative symptoms in schizophrenia.
                      Phosphodiesterase 10A (PDE10A), an enzyme that is
                      highlyexpressed in the striatum, modulates both dopamine D2-
                      and D1-dependent signaling.METHODS:We assessed whether
                      augmentation of D1signaling by the PDE10 inhibitor RG7203
                      enhances imagingand behavioral markers of reward functions
                      in patients with schizophrenia and negative symptoms. In a
                      3-period,double-blind, crossover study, we investigated the
                      effects of RG7203 (5 mg and 15 mg doses) and placebo
                      asadjunctive treatment to stable background antipsychotic
                      treatment in patients with chronic schizophrenia
                      withmoderate levels of negative symptoms. Effects on reward
                      functioning and reward-based effortful behavior
                      wereevaluated using the monetary incentive delay task during
                      functional magnetic resonance imaging and the
                      effort-cost-benefit and working memory reinforcement
                      learning tasks.RESULTS:Patients (N= 33; 30 male, mean age6SD
                      36.667.0 years; Positive and Negative Syndrome Scalenegative
                      symptom factor score 23.063.5 at screening) were assessed at
                      three study centers in the United States; 24patients
                      completed the study. RG7203 at 5 mg significantly increased
                      reward expectation–related activity in themonetary
                      incentive delay task, but in the context of significantly
                      decreased overall activity across all task
                      conditions.CONCLUSIONS:In contrast to our expectations,
                      RG7203 significantly worsened reward-based effortful
                      behavior andindices of reward learning. The results do not
                      support the utility of RG7203 as adjunctive treatment for
                      negativesymptoms in patients with schizophrenia.},
      cin          = {INM-7 / IBG-2},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-7-20090406 / I:(DE-Juel1)IBG-2-20101118},
      pnm          = {5252 - Brain Dysfunction and Plasticity (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5252},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {36324430},
      UT           = {WOS:001052353400009},
      doi          = {10.1016/j.bpsgos.2021.03.001},
      url          = {https://juser.fz-juelich.de/record/893885},
}