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Cited by 144Schizophrenia research and treatmentTreatment of Major DepressionNeurotransmitter Receptor Influence on Behavior

Once-weekly D-cycloserine effects on negative symptoms and cognition in schizophrenia: an exploratory study

Open access
GOFF, D, CATHER, C, GOTTLIEB, J, EVINS, A, WALSH, J, RAEKE, L, OTTO, M, SCHOENFELD, D +1 more·2008·Schizophrenia Research
DOI 10.1016/j.schres.2008.08.012PMC PMC2628436
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Abstract

Background Daily dosing with D-cycloserine has inconsistently improved negative symptoms in schizophrenia patients, whereas intermittent dosing significantly facilitated exposure-based therapy in two studies of patients with phobic anxiety. In animal models, single dose administration enhances memory consolidation, but tachyphylaxis develops with repeated dosing. The objective of this exploratory study was to assess whether once-weekly dosing with D-cycloserine will produce persistent improvements in negative symptoms and cognition. Methods Fifty stable adult schizophrenia outpatients treated with any antipsychotic except clozapine were enrolled and 38 were randomized, double-blind, in a parallel-group, 8-week add-on trial of D-cycloserine 50 mg or placebo administered once-weekly. Symptom rating scales and a cognitive battery were administered at baseline and week 8 before the dose of study drug. As an exploratory analysis of memory consolidation, the Logical Memory Test, modified to measure recall after 7 days, was administered at baseline and after the first weekly dose of D-cycloserine. The primary outcome measures were change from baseline to week 8 on the SANS total score and on a composite cognitive score. Results Thirty-three subjects (87%) completed the trial. D-cycloserine significantly improved SANS total scores compared to placebo at week 8. Cognitive performance did not improve with D-cycloserine at 8 weeks. Delayed thematic recall on the Logical Memory Test was significantly improved with the first dose of D-cycloserine compared to placebo. Performance on immediate thematic recall and item recall on the Logical Memory Test did not differ between treatments. Conclusions Once-weekly dosing with D-cycloserine for 8 weeks produced persistent improvement of negative symptoms compared to placebo, although statistical significance was, in part, the result of worsening of negative symptoms with placebo. Consistent with animal models, a single dose of D-cycloserine facilitated memory consolidation tested after 7 days on a test of thematic recall. These results must be considered preliminary since a number of outcomes were examined without correction for multiple tests. These findings suggest that once-weekly dosing with D-cycloserine for the treatment of negative symptoms merits further study, as do D-cycloserine effects on memory consolidation.

AI snapshot

Written from the paper’s full text.

TL;DR

In stable adult schizophrenia outpatients, once-weekly D-cycloserine 50 mg added to antipsychotics improved negative symptoms versus placebo over 8 weeks but did not improve composite cognition. A single first dose also improved 7-day delayed thematic recall, consistent with an effect on memory consolidation.

Key findings

  • Modified SANS total score improved at week 8 with D-cycloserine versus placebo (p=0.048); response rates were 31.3% with D-cycloserine versus 11.8% with placebo but did not differ significantly (p>0.1). The net SANS reduction was 16.6% (effect size 0.7), reflecting 8% improvement with D-cycloserine and 8% worsening with placebo.
  • Cognitive performance on the composite cognitive battery did not improve with D-cycloserine at 8 weeks.
  • Delayed thematic recall on the Logical Memory Test at week 1, after the first dose, was significantly improved with D-cycloserine versus placebo (F(1,34)=6.77, p=.01, effect size 0.9); immediate thematic recall and immediate or delayed item recall did not differ.
  • PANSS positive symptom subscale and CGI at week 8 did not differ between groups; D-cycloserine was generally well tolerated, with no dropouts directly attributed to its side effects.

Methods

  • Fifty stable adult schizophrenia outpatients on any antipsychotic except clozapine were enrolled; 38 were randomized double-blind in a parallel-group, 8-week add-on trial of once-weekly D-cycloserine 50 mg or placebo, and 33 (87%) completed.
  • Symptom scales (SANS, PANSS, CGI, SAFTEE) and a six-domain cognitive battery were administered at baseline and week 8 before study drug; a modified Logical Memory Test measured delayed thematic recall after 7 days following the first weekly dose.
  • Primary outcomes were change from baseline to week 8 on modified SANS total and composite cognitive score, analyzed with ANCOVA controlling for baseline; exploratory analyses used ANCOVA and t-tests, with no correction for multiple comparisons.

Limitations

  • Stated: the study was exploratory and preliminary; multiple outcomes were examined without correction for multiple tests; the SANS difference was in part due to worsening in the placebo group; the 7-day Logical Memory Test recall condition had not previously been studied or validated; proactive interference from story A may have influenced recall of story B; the standard cognitive battery did not specifically target memory consolidation.
  • Evident from the text: the randomized sample was small (38 randomized, 33 completers) and the trial lasted only 8 weeks, limiting precision and generalizability; patients on clozapine were excluded.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.schres.2008.08.012

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

0 of 38 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Once-weekly D-cycloserine did not improve cognitive performance (composite cognitive score) at 8 weeks compared to placebo.

    “Cognitive performance did not improve with D-cycloserine at 8 weeks.”
    • Also stated in: § Results · plain
      “There was no effect of drug on the cognitive composite at week 8 (Table 2).”
    • Also stated in: § Conclusion · plain
      “Once-weekly D-cycloserine did not improve cognitive functioning after 8 weeks.”
    Quote in the paperSubstantial claim
  • Findingown data

    A single first dose of D-cycloserine significantly improved delayed thematic recall on the Logical Memory Test (7-day delayed recall) compared to placebo.

    “Delayed thematic recall on the Logical Memory Test was significantly improved with the first dose of D-cycloserine compared to placebo.”
    • Also stated in: § Results · plain
      “Compared to placebo, the D-cycloserine group significantly improved on delayed thematic recall of the LMT administered at week 1 which reflected the first dose of study drug (F (1, 34) = 6.77, p = .01, effect size 0.9)”
    • Also stated in: § Conclusion · plain
      “However, an exploratory test of verbal memory following a delay in recall of 7 days significantly improved after the first dose of D-cycloserine.”
    Quote in the paperSubstantial claim
  • Findingown data

    D-cycloserine was generally well-tolerated.

    “D-cycloserine was generally well-tolerated (Table 3).”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the D-cycloserine group, change from baseline on the modified SANS total score did not correlate significantly with age, gender, antipsychotic type, or baseline SANS or PANSS total score.

    “In the D-cycloserine group, change from baseline on the modified SANS total score did not correlate significantly with age, gender, antipsychotic type (typical or atypical), or baseline SANS or PANSS total score.”
    Quote in the paperNot a substantial claim
  • Findingown data

    The 31.3% response rate (at least 20% improvement in modified SANS total score) in D-cycloserine-treated subjects did not differ significantly from the 11.8% response rate in placebo-treated subjects.

    “However, the 31.3% response rate in subjects treated with D-cycloserine did not differ significantly from the 11.8% response rate in the placebo group (p>0.1).”
    Quote in the paperSubstantial claim
  • May combine two claims. 23
  • Classified as probably not a substantial claim. 21

  • May combine two claims.

    Findingown data

    Immediate thematic recall and immediate or delayed item recall on the Logical Memory Test did not differ between D-cycloserine and placebo.

    “Performance on immediate thematic recall and item recall on the Logical Memory Test did not differ between treatments.”
    • Also stated in: § Results · plain
      “but did not differ from the placebo group in immediate thematic recall on the LMT or in immediate or delayed item recall from week 1 (Figure 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Change from baseline to week 8 on the PANSS positive symptom subscale and CGI did not differ between D-cycloserine and placebo groups.

    “The change from baseline to week 8 on the PANSS positive symptom subscale and the CGI at week 8 did not differ between treatment groups (Table 1).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Subjects were randomly assigned in blocks of four using a computerized randomization schedule to placebo or D-cycloserine prepared in identical capsules, and all research personnel were kept blind to treatment assignment.

    “Subjects were randomly assigned in blocks of four using a computerized randomization schedule to placebo or D-cycloserine prepared in identical capsules by the research pharmacy. All research personnel were kept blind to treatment assignment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Thirty-three subjects (87%) completed the 8-week trial.

    “Baseline and week 1 assessments were completed by 37 subjects (97%); 33 subjects (87%) completed week 8.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    These results must be considered preliminary since a number of outcomes were examined without correction for multiple tests.

    “These results must be considered preliminary since a number of outcomes were examined without correction for multiple tests.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The CONSIST trial failed to find efficacy with either glycine or D-cycloserine compared to placebo for negative symptoms or cognitive deficits in 171 schizophrenia patients, although significant differences in outcomes between sites complicate interpretation.

    “More recently, the Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST) failed to find efficacy with either glycine or D-cycloserine compared to placebo for negative symptoms or cognitive deficits in 171 schizophrenia patients, although significant differences in outcomes between sites complicate interpretation of this negative finding (Buchanan, et al., 2007).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Buchanan, et al., 2007

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Because the story at week 1 (story B) was different from that at baseline (story A), proactive interference from story A may have influenced recall of story B.

    “Because the story at week 1 (story B) was different from that at baseline (story A) proactive interference from story A may have influenced recall of story B.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The 7-day recall condition with the LMT was added as an exploratory measure to capture memory consolidation effects, but has not previously been studied or validated as an outcome measure.

    “The use of a 7-day recall condition with the LMT was added as an exploratory measure to capture memory consolidation effects, but has not previously been studied or validated as an outcome measure.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The absence of cognitive effect at week 8 is based on a standard cognitive battery that did not specifically target memory consolidation effects.

    “Finally, the absence of cognitive effect at week 8 is based on a standard cognitive battery that did not specifically target memory consolidation effects.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The significant improvement in delayed but not immediate thematic recall on the LMT following the first administration of D-cycloserine is consistent with animal models in which learning effects of D-cycloserine are first detectable after a 24 hour interval, possibly reflecting the role of NMDA receptors in memory consolidation.

    “The significant improvement in delayed but not immediate thematic recall on the LMT following the first administration of D-cycloserine is consistent with animal models in which learning effects of D-cycloserine are first detectable after a 24 hour interval, possibly reflecting the role of NMDA receptors in memory consolidation (Santini, et al., 2001).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Santini, et al., 2001

      Not checked in the free run.

    • Rests on an assumption: The 7-day delayed recall on the Logical Memory Test measures memory consolidation.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    As the first study of once-weekly dosing in schizophrenia, this study was exploratory and so results must be considered preliminary, particularly since negative symptoms worsened in the placebo group and several outcome measures were examined without correction for multiple comparisons.

    “As the first study of once-weekly dosing in schizophrenia, this study was exploratory and so results must be considered preliminary, particularly since negative symptoms worsened in the placebo group and several outcome measures were examined without correction for multiple comparisons.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: This is the first study of once-weekly dosing with D-cycloserine in schizophrenia.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Pre-treatment with D-cycloserine for 15 days attenuated facilitation in mice of a maze learning task, and increasing the dose from 3 mg/kg to 20 mg/kg did not counter the tolerance.

    “For example, pre-treatment with D-cycloserine for 15 days attenuated facilitation in mice of a maze learning task (Quartermain, et al., 1994). Increasing the D-cycloserine dose from 3 mg/kg to 20 mg/kg did not counter the tolerance produced by 15 days of pre-treatment.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Quartermain, et al., 1994

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Single-dose administration of D-cycloserine consistently produced positive effects on memory and learning, whereas several studies demonstrated tachyphylaxis with repeated administration.

    “Whereas single-dose administration of D-cycloserine consistently produced positive effects on memory and learning, several studies have demonstrated tachyphylaxis with repeated administration.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Elevated concentrations of glycine or D-serine at the glycine recognition site prime the NMDA receptor for removal from the cell surface to the intracellular compartment, a process believed to represent a mechanism for desensitization of NMDA receptors.

    “Recent evidence suggests that elevated concentrations of glycine or D-serine at the glycine recognition site “prime” the NMDA receptor for removal from the cell surface to the intracellular compartment (Nong, et al., 2003). This process of “internalization” is believed to represent a mechanism for desensitization of NMDA receptors.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Nong, et al., 2003

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Because the SANS rating at week 8 was performed prior to the weekly D-cycloserine dose, intermittent dosing with D-cycloserine may produce persistent alterations in excitatory synapses involved in expression of negative symptoms.

    “Furthermore, because the SANS rating at week 8 was performed prior to the weekly D-cycloserine dose, this finding indicates that intermittent dosing with D-cycloserine may produce persistent alterations in excitatory synapses involved in expression of negative symptoms.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Because treatment groups were comparable at baseline and in change scores on other symptom ratings, the significant difference in SANS scores at week 8 most likely represents a true drug effect and is not the result of clinical worsening unique to the placebo group.

    “Because the treatment groups were comparable in all demographic characteristics and on all clinical measures at baseline, as well as in change scores on other symptom ratings, it is most likely that the significant difference in SANS scores at week 8 represents a true drug effect and is not the result of clinical worsening unique to the placebo group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Several studies of D-cycloserine for negative symptoms were negative, and D-cycloserine did not achieve significant efficacy in a meta-analysis.

    “The glycine-site partial agonist, D-cycloserine, was effective for negative symptoms in one placebo-controlled trial in 47 schizophrenia patients (Goff, et al., 1999b), whereas several studies were negative (Duncan, et al., 2004, Goff, et al., 2005, van Berckel, et al., 1999) and D-cycloserine did not achieve significant efficacy in the meta-analysis (Tuominen, et al., 2005).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Duncan, et al., 2004

      Not checked in the free run.

    • cites Goff, et al., 2005

      Not checked in the free run.

    • cites Tuominen, et al., 2005

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Memory effects of D-cycloserine do not become evident until 24 hours after learning, a delay believed to reflect NMDA receptor modification of memory consolidation.

    “Memory effects of D-cycloserine do not become evident until 24 hours after learning, a delay that is believed to reflect NMDA receptor modification of memory consolidation (Santini, et al., 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Santini, et al., 2001

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Because the study was exploratory, no corrections were made for multiple comparisons.

    “Because the study was exploratory in nature, no corrections were made for multiple comparisons.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Antipsychotics have been shown to alter NMDA sensitivity by a variety of mechanisms, including alterations in NMDA receptor density and subunit composition, changes in pharmacologic sensitivity of the glycine site, and in regulation of glutamate release.

    “In addition, antipsychotics have been shown to alter NMDA sensitivity by a variety of mechanisms, including alterations in NMDA receptor density and subunit composition, changes in pharmacologic sensitivity of the glycine site, and in regulation of glutamate release (Goff, et al., 2002, Millan, 2005).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Goff, et al., 2002

      Not checked in the free run.

    • cites Millan, 2005

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In animals, spatial memory and visual recognition tests have also shown enhancement following a single dose of D-cycloserine, suggesting that a range of cognitive functions may respond in a similar pattern to D-cycloserine.

    “In animals, spatial memory and visual recognition tests have also shown enhancement following a single dose of D-cycloserine (Matsuoka and Aigner, 1996, Quartermain, et al., 1994) suggesting that a range of cognitive functions may respond in a similar pattern to D-cycloserine.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Matsuoka and Aigner, 1996

      Not checked in the free run.

    • cites Quartermain, et al., 1994

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    D-cycloserine is a relatively selective partial agonist at the glycine site with approximately 35%-68% activity compared to glycine for NMDA receptors containing NR2A or NR2B subunits and 192% activity for receptors containing the NR2C subunit.

    “D-cycloserine is a relatively selective partial agonist at the glycine site with approximately 35%-68% activity compared to glycine for NMDA receptors containing NR2A or NR2B subunits and 192% activity for receptors containing the NR2C subunit (Sheinin, et al., 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sheinin, et al., 2001

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    D-cycloserine pre-treatment was associated with significantly greater improvements in acrophobia symptoms, physiological measures of anxiety, and behavioral ratings one week and three months after treatment in 28 acrophobia patients.

    “D-cycloserine pre-treatment was associated with significantly greater improvements in acrophobia symptoms, physiological measures of anxiety, and behavioral ratings one week and three months after treatment.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ressler, et al., 2004

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Preliminary evidence has suggested that the magnitude of D-cycloserine's effect on negative symptoms might be greater when D-cycloserine is added to first generation antipsychotics than to atypicals.

    “In addition, preliminary evidence has suggested that the magnitude of D-cycloserine’s effect on negative symptoms might be greater when D-cycloserine is added to first generation antipsychotics, as in the daily dosing trial, than to atypicals (Evins, et al., 2002, Goff, et al., 1999a, Goff, et al., 1995).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Evins, et al., 2002

      Not checked in the free run.

    • cites Goff, et al., 1999a

      Not checked in the free run.

    • cites Goff, et al., 1995

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    While negative symptom effects increase over time with repeated dosing, enhancement of memory appears to diminish.

    “While negative symptom effects increase over time with repeated dosing, enhancement of memory appears to diminish.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    D-cycloserine significantly improved all outcome measures following completion of treatment and at 4-week follow-up in 27 patients with social anxiety disorder treated with D-cycloserine 50 mg or placebo before each of 4 weekly cognitive behavioral exposure sessions.

    “Similarly, Hoffman and colleagues (Hofmann, et al., 2006) treated 27 patients with social anxiety disorder with D-cycloserine 50 mg or placebo one hour before each of 4 weekly cognitive behavioral exposure sessions for public speaking anxiety and found that D-cycloserine significantly improved all outcome measures following completion of treatment and at 4-week follow-up.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Hofmann, et al., 2006

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    A single pre-exposure dose of D-cycloserine resulted in partial tolerance to D-cycloserine's facilitative effect on fear extinction, and 5 pre-exposure doses separated by 48 hours fully attenuated the effect.

    “Parnas and colleagues (Parnas, et al., 2005) found that a single pre-exposure dose of D-cycloserine resulted in partial tolerance to D-cycloserine’s facilitative effect on fear extinction and that 5 pre-exposure doses separated by 48 hours fully attenuated the effect.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Parnas, et al., 2005

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In an oral single-dose challenge study in 16 healthy subjects, D-cycloserine 15, 50 and 150 mg achieved maximal plasma levels beginning 30-60 minutes after administration; plasma levels remained stable over the four-hour period of monitoring.

    “In an oral single-dose challenge study in 16 healthy subjects, D-cycloserine 15, 50 and 150 mg achieved maximal plasma levels beginning 30–60 minutes after administration; plasma levels remained stable over the four-hour period of monitoring (van Berckel, et al., 1997).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites van Berckel, et al., 1997

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    D-serine was found to preferentially enhance reversal learning in mice, possibly mediated by long term depression (LTD) of glutamatergic neurotransmission.

    “Recently, the glycine site full agonist, D-serine, was found to preferentially enhance reversal learning in mice, possibly mediated by long term depression (LTD) of glutamatergic neurotransmission (Duffy, et al., 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Duffy, et al., 2007

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    NMDA channel blockade with ketamine increases perseverative errors on the WCST in healthy subjects.

    “Moreover, NMDA channel blockade with ketamine increases perseverative errors on the WCST in healthy subjects (Krystal, et al., 1994).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Krystal, et al., 1994

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    D-cycloserine readily crosses the blood-brain barrier and is cleared by the kidneys unmetabolized with a serum half-life estimated between 7-15 hours.

    “D-cycloserine readily crosses the blood-brain barrier and is cleared by the kidneys unmetabolized with a serum half-life estimated between 7–15 hours (Hanngren, et al., 1961).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Hanngren, et al., 1961

      Not checked in the free run.

31 of 31

  • The paper relies on this without support.

    The 7-day delayed recall on the Logical Memory Test measures memory consolidation.

    “Instead of the usual 30 minute interval for delayed recall we used a 7-day delayed recall to capture the overnight consolidation that is of interest with D-cycloserine.”
    “The use of a 7-day recall condition with the LMT was added as an exploratory measure to capture memory consolidation effects, but has not previously been studied or validated as an outcome measure.”

  • The paper relies on this without support.

    Story themes are more reliably recalled than story items after a prolonged delay and better represent memory performance involved in psychotherapy or rehabilitation interventions.

    “We expected that story themes would be more reliably recalled than story items after such a prolonged delay and would better represent memory performance involved in psychotherapy or rehabilitation interventions.”

  • The paper relies on this without support.

    A one-week interval between D-cycloserine doses avoids tachyphylaxis in schizophrenia patients.

    “We adopted the approach of a one-week interval between doses of D-cycloserine 50 mg from successful trials in anxiety disorders to see if efficacy for cognitive deficits and negative symptoms of schizophrenia could be enhanced in an eight-week add-on trial.”

  • The paper relies on this without support.

    This is the first study of once-weekly dosing with D-cycloserine in schizophrenia.

    “As the first study of once-weekly dosing in schizophrenia, this study was exploratory and so results must be considered preliminary, particularly since negative symptoms worsened in the placebo group and several outcome measures were examined without correction for multiple comparisons.”
4 of 4

Claims other papers make about this one

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Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • ConsistentF(1, 34) = 6.77reported p = .01 · recomputed p = .014

    “F (1, 34) = 6.77, p = .01”

  • ConsistentF(1, 29) = 1.8reported p = .19 · recomputed p = .190

    “F (1, 29) = 1.80, p = .19”

2 of 2

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Self-check results appear here once an independent check has confirmed them.

Cites

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Research works printed but not linked: 1

  1. Spreen O Strauss E A compendium of neuropsychological tests New York Oxford University Press 1991

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Authors
GOFF, D., CATHER, C., GOTTLIEB, J., EVINS, A., WALSH, J., RAEKE, L., OTTO, M., SCHOENFELD, D., & GREEN, M.
Affiliations
  • Harvard University (US)
  • Massachusetts General Hospital (US)
  • Boston University (US)
  • University of California, Los Angeles (US)
Corresponding author
GOFF, D
ORCID
Venue
Schizophrenia Research
Publisher
Elsevier BV
Published
2008-12
Volume
106
Issue
2-3
Pages
320-327
ISSN
0920-9964 (ISSN-L)
DOI
10.1016/j.schres.2008.08.012
PMC
PMC2628436
OpenAlex
W2123774291
Semantic Scholar
caddc13933f8f6d72e1821bb548ba003b690723f
Cited by
144
References
39
Citations by year
2026: 1 · 2025: 6 · 2024: 3 · 2023: 1 · 2022: 7 · 2021: 8 · 2020: 5 · 2019: 6 · 2018: 10 · 2017: 8 · 2016: 6 · 2015: 11 · 2014: 7 · 2013: 14 · 2012: 15
FWCI
8.43
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Schizophrenia Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (P50MH060450, 2 P50 MH0060450-08A1, K24MH002025)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
D-cycloserine, schizophrenia
MeSH terms
Adolescent, Adult, Aged, Cognition Disorders, Cycloserine, Drug Administration Schedule, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Placebos, Psychiatric Status Rating Scales, Schizophrenia, Schizophrenic Psychology, Antipsychotic Agents

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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