CONTEXT: Imaging and post-mortem studies suggest that frontal lobe intracortical myelination is dysregulated in schizophrenia (SZ). Prior MRI studies suggested that early in the treatment of SZ, antipsychotic medications initially increase frontal lobe intracortical myelin (ICM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of ICM decline in chronic SZ is due to medication non-adherence or pharmacokinetics, it may be modifiable by long acting injection (LAI) formulations. OBJECTIVES: Assess the effect of risperidone formulation on the ICM trajectory during a six-month randomized trial of LAI (RLAI) versus oral (RisO) in first-episode SZ subjects. DESIGN: Two groups of SZ subjects (RLAI, N=9; and RisO, N=13) matched on pre-randomization oral medication exposure were prospectively examined at baseline and 6 months later, along with 12 healthy controls (HCs). Frontal lobe ICM volume was assessed using inversion recovery (IR) and proton density (PD) MRI images. Medication adherence was tracked. MAIN OUTCOME MEASURE: ICM volume change scores were adjusted for the change in the HCs. RESULTS:ICM volume increased significantly (p=.005) in RLAI and non-significantly (p=.39) in the RisO groups compared with that of the healthy controls. A differential between-group treatment effect was at a trend level (p=.093). SZ subjects receiving RLAI had better medication adherence and more ICM increases (chi-square p<.05). CONCLUSIONS: The results suggest that RLAI may promote ICM development in first-episode SZ patients. Better adherence and/or pharmacokinetics provided by LAI may modify the ICM trajectory. In vivo MRI myelination measures can help clarify pharmacotherapeutic mechanisms of action.
RCT Entities:
CONTEXT: Imaging and post-mortem studies suggest that frontal lobe intracortical myelination is dysregulated in schizophrenia (SZ). Prior MRI studies suggested that early in the treatment of SZ, antipsychotic medications initially increase frontal lobe intracortical myelin (ICM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of ICM decline in chronic SZ is due to medication non-adherence or pharmacokinetics, it may be modifiable by long acting injection (LAI) formulations. OBJECTIVES: Assess the effect of risperidone formulation on the ICM trajectory during a six-month randomized trial of LAI (RLAI) versus oral (RisO) in first-episode SZ subjects. DESIGN: Two groups of SZ subjects (RLAI, N=9; and RisO, N=13) matched on pre-randomization oral medication exposure were prospectively examined at baseline and 6 months later, along with 12 healthy controls (HCs). Frontal lobe ICM volume was assessed using inversion recovery (IR) and proton density (PD) MRI images. Medication adherence was tracked. MAIN OUTCOME MEASURE: ICM volume change scores were adjusted for the change in the HCs. RESULTS: ICM volume increased significantly (p=.005) in RLAI and non-significantly (p=.39) in the RisO groups compared with that of the healthy controls. A differential between-group treatment effect was at a trend level (p=.093). SZ subjects receiving RLAI had better medication adherence and more ICM increases (chi-square p<.05). CONCLUSIONS: The results suggest that RLAI may promote ICM development in first-episode SZ patients. Better adherence and/or pharmacokinetics provided by LAI may modify the ICM trajectory. In vivo MRI myelination measures can help clarify pharmacotherapeutic mechanisms of action.
Authors: Patrick R Hof; Vahram Haroutunian; Christina Copland; Kenneth L Davis; Joseph D Buxbaum Journal: Neurochem Res Date: 2002-10 Impact factor: 3.996
Authors: D G Robinson; M G Woerner; J M Alvir; S Geisler; A Koreen; B Sheitman; M Chakos; D Mayerhoff; R Bilder; R Goldman; J A Lieberman Journal: Am J Psychiatry Date: 1999-04 Impact factor: 18.112
Authors: Y Hakak; J R Walker; C Li; W H Wong; K L Davis; J D Buxbaum; V Haroutunian; A A Fienberg Journal: Proc Natl Acad Sci U S A Date: 2001-04-10 Impact factor: 11.205
Authors: George Bartzokis; Keith H Nuechterlein; Po H Lu; Michael Gitlin; Steven Rogers; Jim Mintz Journal: Biol Psychiatry Date: 2003-03-01 Impact factor: 13.382
Authors: Christopher D Rowley; Manpreet Sehmbi; Pierre-Louis Bazin; Christine L Tardif; Luciano Minuzzi; Benicio N Frey; Nicholas A Bock Journal: Hum Brain Mapp Date: 2017-04-30 Impact factor: 5.038
Authors: Marc De Hert; Jan Sermon; Paul Geerts; Kristof Vansteelandt; Joseph Peuskens; Johan Detraux Journal: CNS Drugs Date: 2015-08 Impact factor: 5.749
Authors: Kenneth L Subotnik; Laurie R Casaus; Joseph Ventura; John S Luo; Gerhard S Hellemann; Denise Gretchen-Doorly; Stephen Marder; Keith H Nuechterlein Journal: JAMA Psychiatry Date: 2015-08 Impact factor: 21.596
Authors: Evelyn M R Lake; Eric A Steffler; Christopher D Rowley; Manpreet Sehmbi; Luciano Minuzzi; Benicio N Frey; Nicholas A Bock Journal: Eur Arch Psychiatry Clin Neurosci Date: 2016-09-14 Impact factor: 5.270
Authors: Won Jong Chwa; Todd A Tishler; Catalina Raymond; Cathy Tran; Faizan Anwar; J Pablo Villablanca; Joseph Ventura; Kenneth L Subotnik; Keith H Nuechterlein; Benjamin M Ellingson Journal: Schizophr Res Date: 2020-05-31 Impact factor: 4.939
Authors: Valentina Citton; Angela Favaro; Vera Bettini; Joseph Gabrieli; Gabriella Milan; Nella Augusta Greggio; Jan D Marshall; Jürgen K Naggert; Renzo Manara; Pietro Maffei Journal: Orphanet J Rare Dis Date: 2013-02-13 Impact factor: 4.123
Authors: Lena Palaniyappan; Ali Al-Radaideh; Olivier Mougin; Penny Gowland; Peter F Liddle Journal: Neuropsychopharmacology Date: 2013-04-04 Impact factor: 7.853