TY - JOUR
T1 - The effect of high vs. low dose lurasidone on eye movement biomarkers of prefrontal abilities in treatment-resistant schizophrenia
AU - Karpouzian-Rogers, Tatiana
AU - Stocks, Jane
AU - Meltzer, Herbert Y.
AU - Reilly, James L.
N1 - Funding Information:
Herbert Meltzer receives, or has received, other grant support from ACADIA , Allergan , Dainippon Sumitomo , Sunovion , Eli Lilly , Janssen, Lundbeck, Neurocrine, and Reviva. He also receives support from the Weisman Family Foundation . None of the other authors have potential conflicts of interest.
Funding Information:
This study was supported by a grant from Sunovion , a subsidiary of Dainippon Sumitomo , which developed and markets lurasidone, and was registered on www.clinicaltrials.gov/ ( NCT01569659 ). The corresponding author was supported by a fellowship from the Dolores Zohrab Liebmann Fund .
Funding Information:
This study was supported by a grant from Sunovion, a subsidiary of Dainippon Sumitomo, which developed and markets lurasidone, and was registered on www.clinicaltrials.gov/ (NCT01569659). The corresponding author was supported by a fellowship from the Dolores Zohrab Liebmann Fund.Herbert Meltzer receives, or has received, other grant support from ACADIA, Allergan, Dainippon Sumitomo, Sunovion, Eli Lilly, Janssen, Lundbeck, Neurocrine, and Reviva. He also receives support from the Weisman Family Foundation. None of the other authors have potential conflicts of interest.We would like to acknowledge the research staff at the Northwestern University's Clinical Research Program for assistance with study coordination and data collection. We would like to thank our participants for volunteering their time.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2020/1
Y1 - 2020/1
N2 - Objective: Eye movement (EM) measures can serve as biomarkers to evaluate pharmacological effects on brain systems involved in cognition. In recent onset schizophrenia, antipsychotic treatment can improve attentional control on the antisaccade task and exacerbate working memory impairment on the memory guided saccade task; effects in treatment-resistant schizophrenia (TRS) are less clear. This study evaluated the effects of high versus low dose lurasidone on EM performance in TRS. Methods: TRS patients completed EM testing: 1) at baseline, on existing medication regimen (n = 42), 2) after 6 weeks of low dose (80 mg) lurasidone (n = 38), 3) after 12 weeks following randomization to low (80 mg) or high dose (240 mg) lurasidone (n = 27), and 4) after 24 weeks of treatment (n = 23). EM testing included prosaccade, antisaccade, and memory guided saccade tasks. Results: Six weeks of lurasidone resulted in increased prosaccade saccade latency and reduced antisaccade errors, with no change in memory guided saccade accuracy. After randomization, prosaccade and antisaccade latencies increased in only the high dose group, with no change in antisaccade errors in both groups. Memory guided saccade error increased in the high dose group and remained stable in the low dose group. Conclusion: Among TRS, stabilization on low dose lurasidone was associated with improved executive control of attention reflected by reduced antisaccade errors. High dose lurasidone resulted in prolonged speed of reflexive and executive shifts of attention and reduced spatial working memory relative to low dose. These findings indicate that EM measures are helpful biomarkers of dose-dependent antipsychotic treatment effects on executive cognitive abilities in TRS.
AB - Objective: Eye movement (EM) measures can serve as biomarkers to evaluate pharmacological effects on brain systems involved in cognition. In recent onset schizophrenia, antipsychotic treatment can improve attentional control on the antisaccade task and exacerbate working memory impairment on the memory guided saccade task; effects in treatment-resistant schizophrenia (TRS) are less clear. This study evaluated the effects of high versus low dose lurasidone on EM performance in TRS. Methods: TRS patients completed EM testing: 1) at baseline, on existing medication regimen (n = 42), 2) after 6 weeks of low dose (80 mg) lurasidone (n = 38), 3) after 12 weeks following randomization to low (80 mg) or high dose (240 mg) lurasidone (n = 27), and 4) after 24 weeks of treatment (n = 23). EM testing included prosaccade, antisaccade, and memory guided saccade tasks. Results: Six weeks of lurasidone resulted in increased prosaccade saccade latency and reduced antisaccade errors, with no change in memory guided saccade accuracy. After randomization, prosaccade and antisaccade latencies increased in only the high dose group, with no change in antisaccade errors in both groups. Memory guided saccade error increased in the high dose group and remained stable in the low dose group. Conclusion: Among TRS, stabilization on low dose lurasidone was associated with improved executive control of attention reflected by reduced antisaccade errors. High dose lurasidone resulted in prolonged speed of reflexive and executive shifts of attention and reduced spatial working memory relative to low dose. These findings indicate that EM measures are helpful biomarkers of dose-dependent antipsychotic treatment effects on executive cognitive abilities in TRS.
KW - Executive control
KW - Eye movement
KW - Treatment-resistant schizophrenia
KW - Working memory
UR - http://www.scopus.com/inward/record.url?scp=85075442781&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85075442781&partnerID=8YFLogxK
U2 - 10.1016/j.schres.2019.10.008
DO - 10.1016/j.schres.2019.10.008
M3 - Article
C2 - 31706786
AN - SCOPUS:85075442781
SN - 0920-9964
VL - 215
SP - 314
EP - 321
JO - Schizophrenia Research
JF - Schizophrenia Research
ER -
