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Task-related fMRI responses to a nicotinic acetylcholine receptor partial agonist in schizophrenia: A randomized trial.
Barch, Deanna M; Marder, Stephen R; Harms, Michael P; Jarskog, L Fredrik; Buchanan, Robert W; Cronenwett, Will; Chen, Li-Shiun; Weiss, Markus; Maguire, Ralph P; Pezous, Nicole; Feuerbach, Dominik; Lopez-Lopez, Cristina; Johns, Donald R; Behrje, Rhett B; Gomez-Mancilla, Baltazar.
Afiliación
  • Barch DM; Department of Psychology, Washington University, St. Louis, MO, USA; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: dbarch@wustl.edu.
  • Marder SR; Semel Institute for Neuroscience at UCLA, Los Angeles, CA, USA; VA Desert Pacific Mental Illness Research, Education, and Clinical Center, Los Angeles, CA, USA. Electronic address: SMarder@mednet.ucla.edu.
  • Harms MP; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: mharms@wustl.edu.
  • Jarskog LF; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: lars_jarskog@med.unc.edu.
  • Buchanan RW; Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: rwbuchanan@mprc.umaryland.edu.
  • Cronenwett W; Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address: w-cronenwett@northwestern.edu.
  • Chen LS; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: chenli@psychiatry.wustl.edu.
  • Weiss M; Novartis Pharma AG, Basel, Switzerland. Electronic address: markus.weiss@novartis.com.
  • Maguire RP; Novartis Pharma AG, Basel, Switzerland. Electronic address: paul.maguire@novartis.com.
  • Pezous N; Novartis Pharma AG, Basel, Switzerland. Electronic address: nicole.pezous@novartis.com.
  • Feuerbach D; Novartis Pharma AG, Basel, Switzerland. Electronic address: dominik.feuerbach@novartis.com.
  • Lopez-Lopez C; Novartis Pharma AG, Basel, Switzerland. Electronic address: cristina.lopez_lopez@novartis.com.
  • Johns DR; Novartis Pharma AG, Basel, Switzerland. Electronic address: donald.johns@biogen.com.
  • Behrje RB; Novartis Pharma AG, Basel, Switzerland. Electronic address: rhett.behrje@novartis.com.
  • Gomez-Mancilla B; Novartis Pharma AG, Basel, Switzerland; Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada. Electronic address: baltazar.gomezmancilla@novartis.com.
Article en En | MEDLINE | ID: mdl-27371157
INTRODUCTION: AQW051, an α7-nicotinic acetylcholine receptor partial agonist, enhanced cognitive function in rodent models of learning and memory. This study evaluated brain activation during performance of a working memory task (WMT) and an episodic memory task (EMT), and the effect of AQW051 on task-related brain activation and performance in subjects with schizophrenia. METHODS: This was a double-blind, randomized, placebo-controlled, multicenter, 2-period cross-over trial (NCT00825539) in participants with chronic, stable schizophrenia. Participants, stratified according to smoking status, were randomized (1:1:1:1:1:1) to 1 of 6 sequence groups that determined the study drug dose (AQW051 7.5mg, 50mg or 100mg) and order of administration versus placebo. The primary outcome was brain activation in a priori target regions of interest (ROIs) during performance of the WMT and EMT, measured using functional magnetic resonance imaging. The effect of AQW051 on task-related (EMT and WMT) brain activation and performance was also assessed, as were safety and tolerability. RESULTS: Overall, 60 of 68 enrolled participants completed the study (AQW051 then placebo: 7.5mg n=9; 50mg n=11; 100mg n=10. Placebo then AQW051: 7.5mg n=10; 50mg n=11; 100mg n=9). Significant task-related brain activation (5% significance level) was observed with placebo. During the WMT, a medium effect size was observed in the inferior prefrontal cortex with AQW051 100mg versus placebo (0.431; p=0.105). During the EMT encoding phase, a large effect size was observed in the anterior hippocampus (0.795; p=0.007) and a medium effect size in the posterior hippocampus (0.476; p=0.079) with AQW051 7.5mg. No other medium/large effect sizes were observed with any dose on either task. Effects on brain activation were generally not associated with changes in cognitive performance. AQW051 was well tolerated with an acceptable safety profile. CONCLUSIONS: Overall, no consistent effects of AQW051 on brain regions involved in the performance of a WMT or EMT were observed; however, this study presents a model for evaluating potential response to pharmacological interventions for cognitive impairment in schizophrenia.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Piridinas / Esquizofrenia / Encéfalo / Imagen por Resonancia Magnética / Agonistas Nicotínicos / Compuestos de Azabiciclo Tipo de estudio: Clinical_trials / Etiology_studies / Prognostic_studies Límite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Prog Neuropsychopharmacol Biol Psychiatry Año: 2016 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Piridinas / Esquizofrenia / Encéfalo / Imagen por Resonancia Magnética / Agonistas Nicotínicos / Compuestos de Azabiciclo Tipo de estudio: Clinical_trials / Etiology_studies / Prognostic_studies Límite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Prog Neuropsychopharmacol Biol Psychiatry Año: 2016 Tipo del documento: Article