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Procognitive Effects of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation in Major Depressive Disorder: Effets procognitifs de la D-cyclosérine en traitement complémentaire par la stimulation thêta-burst intermittente dans le trouble dépressif caractérisé

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Title: Procognitive Effects of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation in Major Depressive Disorder: Effets procognitifs de la D-cyclosérine en traitement complémentaire par la stimulation thêta-burst intermittente dans le trouble dépressif caractérisé
Authors: DeMayo, Marilena M. (AUTHOR), Cole, Jaeden (AUTHOR), Sohn, Myren N. (AUTHOR), Bray, Signe L. (AUTHOR), Harris, Ashley D. (AUTHOR), Patten, Scott B. (AUTHOR), McGirr, Alexander (AUTHOR)
Source: Canadian Journal of Psychiatry. Oct2025, Vol. 70 Issue 10, p750-758. 9p.
Subjects: Cycloserine, Methyl aspartate receptors, Cognitive ability, Cognition disorders, Medical protocols, Clinical trials, Transcranial magnetic stimulation, Mental depression
Abstract (English): Objective: Major depressive disorder (MDD) is associated with cognitive impairments that persist despite successful treatment. Transcranial magnetic stimulation is a noninvasive treatment for MDD that is associated with small procognitive effects on working memory and executive function. We hypothesized that pairing stimulation with N-methyl-D-aspartate (NMDA) receptor agonism would enhance the effects of stimulation and its procognitive effects. Method: The effect of NMDA receptor agonism (D-cycloserine, 100 mg) on cognitive performance was tested in two randomized double-blind placebo-controlled trials: (1) acute effects of in the absence of stimulation (n = 20 healthy participants) and (2) a treatment study of individuals with MDD (n = 50) randomized to daily intermittent theta-burst stimulation (iTBS) with placebo or D-cycloserine for 2 weeks. Cognitive function was measured using the THINC-it battery, comprised of the Perceived Deficits Questionnaire, the Choice Reaction Time, the Trail Making Test, the Digit Symbol Substitution Test, and the 1-Back tests. Results: D-cycloserine had no acute effect on cognition compared to placebo. iTBS + D-cycloserine was associated with significant improvements in subjective cognitive function and correct responses on the 1-Back when compared to iTBS + placebo. Improvements in subjective cognition paralleled depressive symptoms improvement, however 1-Back improvements were not attributable to improvement in depression. Conclusions: An intersectional strategy pairing iTBS with NMDA receptor agonism may restore cognitive function in MDD. [ABSTRACT FROM AUTHOR]
Abstract (French): Le trouble dépressif caractérisé (TDC) est associé à des déficits cognitifs qui persistent malgré la réussite du traitement. La stimulation magnétique transcrânienne est un traitement non invasif du TDC qui est associé à de faibles effets procognitifs sur la mémoire à court terme et la fonction exécutive. Nous avons émis l'hypothèse que l'association de la stimulation et de l'agonisme des récepteurs NMDA renforcerait les effets de la stimulation et ses effets positifs sur les performances cognitives. L'effet de l'agonisme des récepteurs NMDA (D-cyclosérine, 100 mg) sur les performances cognitives a été testé dans deux essais randomisés à double insu et contrôlés par placebo: (1) les effets aigus en l'absence de stimulation (n = 20 participants sains); (2) une étude sur le traitement des personnes atteintes de TDC (n = 50) réparties aléatoirement pour recevoir une stimulation thêta-burst intermittente (STBi) associée au placebo ou à la D-cyclosérine pendant deux semaines. La fonction cognitive a été mesurée à l'aide de l'outil THINC-it, composé du Perceived Deficits Questionnaire, de la mesure du temps de réaction de choix, du Trail Making Test, du Digit Symbol Substitution Test et du One-Back Test. La D-cyclosérine n'a eu aucun effet aigu sur la cognition par rapport au placebo. L'association STBi-D-cyclosérine a été associée à des améliorations significatives de la fonction cognitive subjective et à des bonnes réponses au One-Back Test par rapport à l'association STBi-placebo. Les améliorations sur le plan de la cognition subjective étaient parallèles à l'amélioration des symptômes dépressifs, mais la meilleure performance au One-Back Test n'était pas attribuable à l'amélioration des symptômes dépressifs. Il se peut qu'une stratégie intersectionnelle associant la STBi à l'agonisme des récepteurs NMDA restaure la fonction cognitive chez les personnes souffrant de TDC. [ABSTRACT FROM AUTHOR]
Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Procognitive Effects of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation in Major Depressive Disorder: Effets procognitifs de la D-cyclosérine en traitement complémentaire par la stimulation thêta-burst intermittente dans le trouble dépressif caractérisé
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  Data: <searchLink fieldCode="AR" term="%22DeMayo%2C+Marilena+M%2E%22">DeMayo, Marilena M.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cole%2C+Jaeden%22">Cole, Jaeden</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sohn%2C+Myren+N%2E%22">Sohn, Myren N.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bray%2C+Signe+L%2E%22">Bray, Signe L.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Harris%2C+Ashley+D%2E%22">Harris, Ashley D.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Patten%2C+Scott+B%2E%22">Patten, Scott B.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22McGirr%2C+Alexander%22">McGirr, Alexander</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Canadian+Journal+of+Psychiatry%22">Canadian Journal of Psychiatry</searchLink>. Oct2025, Vol. 70 Issue 10, p750-758. 9p.
– Name: Subject
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  Data: <searchLink fieldCode="DE" term="%22Cycloserine%22">Cycloserine</searchLink><br /><searchLink fieldCode="DE" term="%22Methyl+aspartate+receptors%22">Methyl aspartate receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Cognitive+ability%22">Cognitive ability</searchLink><br /><searchLink fieldCode="DE" term="%22Cognition+disorders%22">Cognition disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Medical+protocols%22">Medical protocols</searchLink><br /><searchLink fieldCode="DE" term="%22Clinical+trials%22">Clinical trials</searchLink><br /><searchLink fieldCode="DE" term="%22Transcranial+magnetic+stimulation%22">Transcranial magnetic stimulation</searchLink><br /><searchLink fieldCode="DE" term="%22Mental+depression%22">Mental depression</searchLink>
– Name: Abstract
  Label: Abstract (English)
  Group: Ab
  Data: Objective: Major depressive disorder (MDD) is associated with cognitive impairments that persist despite successful treatment. Transcranial magnetic stimulation is a noninvasive treatment for MDD that is associated with small procognitive effects on working memory and executive function. We hypothesized that pairing stimulation with N-methyl-D-aspartate (NMDA) receptor agonism would enhance the effects of stimulation and its procognitive effects. Method: The effect of NMDA receptor agonism (D-cycloserine, 100 mg) on cognitive performance was tested in two randomized double-blind placebo-controlled trials: (1) acute effects of in the absence of stimulation (n = 20 healthy participants) and (2) a treatment study of individuals with MDD (n = 50) randomized to daily intermittent theta-burst stimulation (iTBS) with placebo or D-cycloserine for 2 weeks. Cognitive function was measured using the THINC-it battery, comprised of the Perceived Deficits Questionnaire, the Choice Reaction Time, the Trail Making Test, the Digit Symbol Substitution Test, and the 1-Back tests. Results: D-cycloserine had no acute effect on cognition compared to placebo. iTBS + D-cycloserine was associated with significant improvements in subjective cognitive function and correct responses on the 1-Back when compared to iTBS + placebo. Improvements in subjective cognition paralleled depressive symptoms improvement, however 1-Back improvements were not attributable to improvement in depression. Conclusions: An intersectional strategy pairing iTBS with NMDA receptor agonism may restore cognitive function in MDD. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label: Abstract (French)
  Group: Ab
  Data: Le trouble dépressif caractérisé (TDC) est associé à des déficits cognitifs qui persistent malgré la réussite du traitement. La stimulation magnétique transcrânienne est un traitement non invasif du TDC qui est associé à de faibles effets procognitifs sur la mémoire à court terme et la fonction exécutive. Nous avons émis l'hypothèse que l'association de la stimulation et de l'agonisme des récepteurs NMDA renforcerait les effets de la stimulation et ses effets positifs sur les performances cognitives. L'effet de l'agonisme des récepteurs NMDA (D-cyclosérine, 100 mg) sur les performances cognitives a été testé dans deux essais randomisés à double insu et contrôlés par placebo: (1) les effets aigus en l'absence de stimulation (n = 20 participants sains); (2) une étude sur le traitement des personnes atteintes de TDC (n = 50) réparties aléatoirement pour recevoir une stimulation thêta-burst intermittente (STBi) associée au placebo ou à la D-cyclosérine pendant deux semaines. La fonction cognitive a été mesurée à l'aide de l'outil THINC-it, composé du Perceived Deficits Questionnaire, de la mesure du temps de réaction de choix, du Trail Making Test, du Digit Symbol Substitution Test et du One-Back Test. La D-cyclosérine n'a eu aucun effet aigu sur la cognition par rapport au placebo. L'association STBi-D-cyclosérine a été associée à des améliorations significatives de la fonction cognitive subjective et à des bonnes réponses au One-Back Test par rapport à l'association STBi-placebo. Les améliorations sur le plan de la cognition subjective étaient parallèles à l'amélioration des symptômes dépressifs, mais la meilleure performance au One-Back Test n'était pas attribuable à l'amélioration des symptômes dépressifs. Il se peut qu'une stratégie intersectionnelle associant la STBi à l'agonisme des récepteurs NMDA restaure la fonction cognitive chez les personnes souffrant de TDC. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Data: <i>Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1177/07067437241293984
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        Text: English
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      – SubjectFull: Cycloserine
        Type: general
      – SubjectFull: Methyl aspartate receptors
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      – SubjectFull: Cognitive ability
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      – SubjectFull: Cognition disorders
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      – SubjectFull: Medical protocols
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      – SubjectFull: Clinical trials
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      – SubjectFull: Transcranial magnetic stimulation
        Type: general
      – SubjectFull: Mental depression
        Type: general
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      – TitleFull: Procognitive Effects of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation in Major Depressive Disorder: Effets procognitifs de la D-cyclosérine en traitement complémentaire par la stimulation thêta-burst intermittente dans le trouble dépressif caractérisé
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              Text: Oct2025
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