d-Cycloserine augmentation of cognitive remediation in schizophrenia.
d-Cycloserine (DCS) has been shown to enhance memory and, in a previous trial, once-weekly DCS improved negative symptoms in schizophrenia subjects. We hypothesized that DCS combined with a cognitive remediation (CR) program would improve memory of a practiced auditory discrimination task and that gains would generalize to performance on unpracticed cognitive tasks. Stable, medicated adult schizophrenia outpatients participated in the Brain Fitness CR program 3-5 times per week for 8weeks. Subjects were randomly assigned to once-weekly adjunctive treatment with DCS (50mg) or placebo administered before the first session each week. Primary outcomes were performance on an auditory discrimination task, the MATRICS cognitive battery composite score and the Scale for the Assessment of Negative Symptoms (SANS) total score. 36 subjects received study drug and 32 completed the trial (average number of CR sessions=26.1). Performance on the practiced auditory discrimination task significantly improved in the DCS group compared to the placebo group. DCS was also associated with significantly greater negative symptom improvement for subjects symptomatic at baseline (SANS score ≥20). However, improvement on the MATRICS battery was observed only in the placebo group. Considered with previous results, these findings suggest that DCS augments CR and alleviates negative symptoms in schizophrenia patients. However, further work is needed to evaluate whether CR gains achieved with DCS can generalize to other unpracticed cognitive tasks.
Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA; Child and Adolescent Psychiatry Department, NYU Langone Medical Center, One Park Avenue, New York City, NY 10016, USA. Electronic address: ccain@nki.rfmh.org.
Christopher K
CK
Cain
Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA. Electronic address: mmccue@nki.rfmh.org.
Margaret
M
McCue
Psychiatry Department, NYU Langone Medical Center, 550 First Avenue, New York City, NY 10016, USA. Electronic address: iruma.bello@nyumc.org.
Iruma
I
Bello
Psychiatry Department, Harvard Medical School, 401 Park Drive, Boston, MA 02215, USA. Electronic address: tcreedon@brandeis.edu.
Timothy
T
Creedon
Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA. Electronic address: tang@nki.rfmh.org.
Dei-In
DI
Tang
Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA. Electronic address: laska@nki.rfmh.org.
Eugene
E
Laska
Psychiatry Department, NYU Langone Medical Center, 550 First Avenue, New York City, NY 10016, USA; Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA. Electronic address: DGoff@nki.rfmh.org.
Donald C
DC
Goff
D000161:Acoustic Stimulation; D000328:Adult; D000963:Antimetabolites / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000534:rehabilitation; D015928:Cognitive Behavioral Therapy / Q000379:methods; D003523:Cycloserine / Q000627:therapeutic use*; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy / Q000534:rehabilitation; D016037:Single-Blind Method
D000963:Antimetabolites; D003523:Cycloserine
Cognitive remediation; MATRICS; Memory; SANS; Schizophrenia; d-Cycloserine