Sustained Modafinil Treatment Effects on Control-Related Gamma Oscillatory Power in Schizophrenia.
Control-related cognitive processes such as rule selection and maintenance are associated with cortical oscillations in the gamma range, and modulated by catecholamine neurotransmission. Control-related gamma power is impaired in schizophrenia, and an understudied treatment target. It remains unknown whether pro-catecholamine pharmacological agents augment control-related gamma oscillations in schizophrenia. We tested the effects of 4-week fixed-dose daily adjunctive modafinil (MOD) 200 mg, in a randomized double-blind, placebo-controlled, parallel-groups design. Twenty-seven stable schizophrenia patients performed a cognitive control task during EEG, at baseline and after 4 weeks of treatment. EEG data underwent time-frequency decomposition with Morlet wavelets to determine power of 4-80 Hz oscillations. The modafinil group (n=14), relative to placebo group (n=13), exhibited enhanced oscillatory power associated with high-control rule selection in the gamma range after treatment, with additional effects during rule maintenance in gamma and sub-gamma ranges. MOD-treated patients who exhibited improved task performance with treatment also showed greater treatment-related delay period gamma compared with MOD-treated patients without improved performance. This is the first evidence in schizophrenia of augmentation of cognition-related gamma oscillations by an FDA-approved agent with therapeutic potential. Gamma oscillations represent a novel treatment target in this disorder, and modulation of catecholamine signaling may represent a viable strategy at this target.
Department of Psychiatry, University of California, San Francisco School of Medicine, and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
Michael J
MJ
Minzenberg
Department of Psychiatry, Stanford University School of Medicine, and Palo Alto Veterans Affairs Medical Center, Palo Alto, CA, USA.
Jong H
JH
Yoon
Department of Psychiatry, University of California, San Francisco School of Medicine, and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
Yaoan
http://orcid.org/0000-0001-5858-6161
Y
Cheng
Department of Psychiatry, University of California, Davis School of Medicine, Sacramento, CA, USA.|Program in Neuroscience, Center for Neuroscience, University of California, Davis, CA, USA.
Cameron S
CS
Carter
D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors; D004311:Double-Blind Method; D004569:Electroencephalography; D056344:Executive Function / Q000187:drug effects* / Q000502:physiology; D005260:Female; D065818:Gamma Rhythm / Q000187:drug effects*; D006801:Humans; D008297:Male; D000077408:Modafinil; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D016896:Treatment Outcome; D055815:Young Adult
D001559:Benzhydryl Compounds; D050483:Dopamine Plasma Membrane Transport Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D000077408:Modafinil