d-Cycloserine and performance under different states of anxiety in healthy volunteers

Bailey, J. A.; Papadopoulos, A.; Lingford-Hughes, AR; Nutt, DJ

doi:10.1007/s00213-007-0817-9

Cited by 33 publications

(40 citation statements)

References 27 publications

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“…This suggests that augmenting NMDAR signaling facilitated the encoding of stimulus-outcome contingencies, possibly by accelerating or augmenting LTP at DMS synapses. Our findings of enhanced acquisition of the WPT and IIT are consistent with other findings of enhanced incremental learning following DCS administration, including on category learning (28), motor learning (25), and mental rotation learning tasks (47).…”

Section: Discussionsupporting

confidence: 92%

Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain

Forsyth

Bachman

Mathalon

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Experience-dependent plasticity is a fundamental property of the brain. It is critical for everyday function, is impaired in a range of neurological and psychiatric disorders, and frequently depends on long-term potentiation (LTP). Preclinical studies suggest that augmenting N-methyl-D-aspartate receptor (NMDAR) signaling may promote experience-dependent plasticity; however, a lack of noninvasive methods has limited our ability to test this idea in humans until recently. We examined the effects of enhancing NMDAR signaling using D-cycloserine (DCS) on a recently developed LTP EEG paradigm that uses high-frequency visual stimulation (HFvS) to induce neural potentiation in visual cortex neurons, as well as on three cognitive tasks: a weather prediction task (WPT), an information integration task (IIT), and a n-back task. The WPT and IIT are learning tasks that require practice with feedback to reach optimal performance. The n-back assesses working memory. Healthy adults were randomized to receive DCS (100 mg; n = 32) or placebo (n = 33); groups were similar in IQ and demographic characteristics. Participants who received DCS showed enhanced potentiation of neural responses following repetitive HFvS, as well as enhanced performance on the WPT and IIT. Groups did not differ on the n-back. Augmenting NMDAR signaling using DCS therefore enhanced activitydependent plasticity in human adults, as demonstrated by lasting enhancement of neural potentiation following repetitive HFvS and accelerated acquisition of two learning tasks. Results highlight the utility of considering cellular mechanisms underlying distinct cognitive functions when investigating potential cognitive enhancers.D-cycloserine | NMDA receptor | neuroplasticity | long-term potentiation | learning E xperience-dependent neuroplasticity is the capacity of the brain to change in response to environmental input, learning, and use. It is a fundamental property of the brain and is critical for everyday functioning. It allows us to learn and remember patterns, predict and obtain reward, and refine and accelerate response selection for adaptive behavior (1). During development, experience-dependent plasticity interacts with genetic programming to organize neurons into the structurally and functionally connected circuits that characterize a mature brain. Although this basic circuitry is established by early adulthood, experience-dependent plasticity continues to shape connectivity within these circuits such that important inputs and action outputs are represented by larger and more coordinated populations of neurons. Given that these changes are the primary means through which the adult brain enables new behavior and that such plasticity is impaired in a range of neurological and psychiatric disorders (2), identifying manipulations that can harness experiencedependent plasticity offers exciting possibilities. Here, we tested whether augmenting N-methyl-D-aspartate receptor (NMDAR) activity could enhance experience-dependent plasticity in the adult human brain.The ...

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Section: Discussionsupporting

confidence: 92%

Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain

Forsyth

Bachman

Mathalon

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…A recent study in humans by Bailey et al [35] examined the effects of 50 mg DCS on learning of a Manikin task that requires participants to cognitively manipulate a humanoid shape to determine which hand is holding a paddle. A performance advantage was found for 50 mg of DCS versus placebo for this task, but notably the effect was found only in individuals who had not undergone anxiety provocation from 7.5% CO 2 inhalation, suggesting that this performance enhancement may be very sensitive to other influences.…”

Section: Discussionmentioning

confidence: 99%

“…A performance advantage was found for 50 mg of DCS versus placebo for this task, but notably the effect was found only in individuals who had not undergone anxiety provocation from 7.5% CO 2 inhalation, suggesting that this performance enhancement may be very sensitive to other influences. Nonetheless, the study by Bailey et al [35] does suggest some immediate performance-enhancing cognitive effects for DCS. We did not hypothesize such effects, but we cannot rule out that trends in our data for immediate memory performance on the HVLT do not reflect similar facilitative effects on in-the-moment cognitive processing.…”

Section: Discussionmentioning

confidence: 99%

Effects of <i>D</i>-Cycloserine Administration on Weekly Nonemotional Memory Tasks in Healthy Participants

Otto

Basden

McHugh

et al. 2008

Psychother Psychosom

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Background: The application of weekly doses of D-cycloserine (DCS) to the enhancement of exposure-based treatments has been a particular achievement of translational research. It is not known, however, whether this enhancement effect can be extended to other forms of learning. In this study, we investigated the relative benefit of DCS versus placebo for enhancing nonemotional verbal and nonverbal memory across weekly trials. Methods: We randomized healthy participants to weekly doses of 50 mg DCS or placebo, with 33 participants completing a 5-week protocol. Participants completed baseline neuropsychological evaluation and then 4 subsequent weeks of repeated learning tasks. Results: No improvement was found in immediate or delayed memory following single doses of DCS for the memory tasks repeated on a weekly basis. Trends for an advantage of DCS were evident for novel word lists given each week. Conclusions: The learning tasks in our study were particularly distinct from the extinction learning paradigms that have shown strong DCS effects, and we were unable to demonstrate useful DCS effects with these nonemotional stimuli. Additional research is needed to elucidate the bounds of DCS augmentation effects on therapeutic learning.

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“…This is based on animal studies indicating DCS functions to aid in the consolidation process of learning (Davis, Ressler, Rothbaum, & Richardson, 2006), though it does not do so by increasing experienced anxiety (Bailey, Papadopoulos, Lingford-Hughes, & Nutt, 2007). Hofmann (2007) discusses the biological and psychological mechanisms thought to be affected during exposure therapy and the effect of DCS on these systems.…”

Section: Pharmacotherapymentioning

confidence: 99%

Social Anxiety Disorder

Emge

Hope

2010

Handbook of Clinical Psychology Competencies

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Social anxiety disorder is a common and debilitating disorder, often leading to complications such as depression, substance abuse and increased suicide risk. During the past two decades, research on the cognitive, behavioral, interpersonal and physiological aspects of social anxiety and subsequent theoretical models have greatly increased our understanding of the nature and maintaining factors for social anxiety disorder. Well-validated assessment procedures including self-report, interview and behavioral measures, are now available. Therapeutic exposure, typically combined with cognitive interventions, is the most established evidencebased treatment. Comparisons of psychosocial treatment to pharmacotherapy and some promising innovative treatment approaches are discussed as well. Emerging work on mechanisms of change suggest that changes in judgments about the probability and costs of negative outcomes are key to clinical change. Competencies for clinicians include expertise with basic cognitive and behavioral therapies, therapeutic exposure and adaptations for the unique characteristics of social anxiety disorder. Especially important is the impact of socially anxious individuals' fears in interpersonal relationships on the therapeutic relationship. Expert competencies include treatment of more severe cases, overcoming extreme social isolation, complex presentations and social anxiety disorder that presents within the context of serious mental illness. Working in a multicultural context, particularly with language differences and sexual minorities are also discussed. Transition to expert competency relies on traditional educational venues, written material and utilizing expert consultation that is available on electronic venues.

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d-Cycloserine and performance under different states of anxiety in healthy volunteers

Cited by 33 publications

References 27 publications

Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain

Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain

Effects of <i>D</i>-Cycloserine Administration on Weekly Nonemotional Memory Tasks in Healthy Participants

Social Anxiety Disorder

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