title: Amphetamine Enhances Gains in Auditory Discrimination Training in Adult Schizophrenia Patients.
abstract: Targeted cognitive training (TCT) of auditory processing enhances higher-order cognition in schizophrenia patients. TCT performance gains can be detected after 1 training session. As a prelude to a potential clinical trial, we assessed a pharmacological augmentation of cognitive therapy (PACT) strategy by testing if the psychostimulant, amphetamine, augments TCT gains in auditory processing speed (APS) in schizophrenia patients and healthy subjects (HS). HS and schizophrenia patients were tested in a screening session (test 1), followed by a double-blind crossover design (tests 2-3), comparing placebo vs amphetamine (10 mg; 7 d between tests). On each test day, 1 hour of Posit Science "Sound Sweeps" training was bracketed by 2- to 4-minute pre- and post-training assessments of APS. Training consisted of a speeded auditory time-order judgment task of successive frequency modulation sweeps. Auditory system "learning" (APS post- vs pre-training) was enhanced by amphetamine (main effect of drug: P < .002; patients: d = 0.56, P < .02; HS: d = 0.39, nonsignificant), and this learning was sustained for at least 1 week. Exploratory analyses assessed potential biomarker predictors of sensitivity to these effects of amphetamine. Amphetamine enhances auditory discrimination learning in schizophrenia patients. We do not know whether gains in APS observed in patients after 1 hour of TCT predict clinical benefits after a full course of TCT. If amphetamine can enhance the therapeutic effects of TCT, this would provide strong support for a "PACT" treatment paradigm for schizophrenia.
authors: Department of Psychiatry, University of California, San Diego, La Jolla, CA.
authors: Neal R
authors: NR
authors: Swerdlow
authors: Department of Psychiatry, University of California, San Diego, La Jolla, CA.|VISN-22 Mental Illness Research, Education, and Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA.
authors: Melissa
authors: M
authors: Tarasenko
authors: Department of Psychiatry, University of California, San Diego, La Jolla, CA.
authors: Savita G
authors: SG
authors: Bhakta
authors: Department of Psychiatry, University of California, San Diego, La Jolla, CA.
authors: Jo
authors: J
authors: Talledo
authors: Department of Psychiatry, University of California, San Diego, La Jolla, CA.
authors: Alexis I
authors: AI
authors: Alvarez
authors: Department of Psychiatry, University of California, San Diego, La Jolla, CA.
authors: Erica L
authors: EL
authors: Hughes
authors: Department of Psychiatry, University of California, San Diego, La Jolla, CA.
authors: Brinda
authors: B
authors: Rana
authors: Department of Psychiatry, University of Minnesota, Minneapolis, MN.
authors: Sophia
authors: S
authors: Vinogradov
authors: Department of Psychiatry, University of California, San Diego, La Jolla, CA.|VISN-22 Mental Illness Research, Education, and Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA.
authors: Gregory A
authors: GA
authors: Light
mesh_terms: D000328:Adult; D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D001307:Auditory Perception / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000209:etiology / Q000534:rehabilitation*; D000072466:Cognitive Remediation / Q000379:methods*; D003131:Combined Modality Therapy; D018592:Cross-Over Studies; D004192:Discrimination, Psychological / Q000502:physiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D012559:Schizophrenia / Q000150:complications / Q000534:rehabilitation*
chemical_list: D000697:Central Nervous System Stimulants; D000661:Amphetamine
keywords: amphetamine; attention; auditory discrimination; cognitive remediation; schizophrenia