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| Name | Class |
|---|---|
| Medical Research Council | OTHER_GOV |
| Johnson & Johnson Pharmaceutical Research & Development, L.L.C. | INDUSTRY |
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Ketamine's efficacy as an antidepressant is now well established yet the mechanisms underlying its antidepressant effect are yet to be fully described. Work in the animal literature and research in humans is suggestive of specific effects on anhedonia and memory reconsolidation. In this study the investigators will further explore the effects of ketamine on learning and memory as well as measuring the associated changes at neural level in a sample of healthy volunteers. Participants will be assigned to receive ketamine or placebo and complete a set of tasks which will allow the investigators to quantify the effect of ketamine on learning about reward and punishment and memory for learned reward associations 24 hours after ketamine infusion. This study will help the investigators to understand the basis of ketamine's antidepressant effects and aid the development of new treatments for depression.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ketamine | Experimental | Participants in this arm will receive a single intravenous, antidepressant dose of ketamine hydrochloride (0.5mg/kg) |
|
| Placebo | Placebo Comparator | Participants in this arm will receive a single intravenous injection of an inactive placebo (0.9% sodium chloride). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketamine Hydrochloride | Drug | Ketamine is a high trapping NMDA receptor antagonist which has rapid and reliable antidepressant effects in patients with major depressive disorder (MDD) who have failed to respond to conventional monoaminergic agents. |
| Measure | Description | Time Frame |
|---|---|---|
| Activation of the habenula during the Pavlovian conditioning task in response to the conditioned stimulus associated with pain stimuli and in response to the receipt of shock. | Blood Oxygen Level Dependent (BOLD) signal in the habenula at the time of the shock-associated conditioned stimulus presentation and at the time of shock delivery. | 24 hours after ketamine infusion |
| Habenula response to the absence of expected reward and the receipt of an unexpected loss (i.e. a negative prediction error signal) in both the reward maximisation and loss minimisation tasks. | BOLD signal in the habenula at the time of outcome presentation in both the reward maximisation and loss minimisation tasks. | 24 hours after ketamine administration |
| Preference for high-reward probability shapes learned after winning money (in the Wheel of Fortune draw) during the preference test. | Proportion of choices where high-reward probability shapes are selected. This will be based on the difference between the perceived reward probability of shapes learned after the winning and losing of money (an area under the curve measure). | +/- 24 hours after ketamine administration |
| Measure | Description | Time Frame |
|---|---|---|
| Ventral striatum response to the expected reward and the omission an unexpected loss (i.e. a positive prediction error signal) in both the reward maximisation and loss minimisation tasks. | BOLD signal in the ventral striatum at the time of outcome presentation in both the reward maximisation and loss minimisation tasks. | 24 hours after ketamine administration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Erdem Pulcu, PhD | Contact | 01865613154 | erdem.pulcu@psych.ox.ac.uk |
| Name | Affiliation | Role |
|---|---|---|
| Catherine Harmer, PhD | University of Oxford | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Oxford | Recruiting | Oxford | OX3 7JZ | United Kingdom |
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| ID | Term |
|---|---|
| D003863 | Depression |
| D003865 | Depressive Disorder, Major |
| D061218 | Depressive Disorder, Treatment-Resistant |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
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| ID | Term |
|---|---|
| D007649 | Ketamine |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
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Participants will be assigned to receive either ketamine or placebo. Ketamine is not being administered for treatment purposes, the purpose is to understand the mechanisms underpinning its effects.
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All members of the study team will be blinded to the condition a participant is allocated to with the exception of the team member responsible for administering the drug/placebo.
| No intervention (placebo) | Other | Placebo injection (0.9% sodium chloride) |
|
| Pupil dilation (measured by an eye tracker device) in response to decision values in the affective memory preference test. | Baseline corrected pupil dilation measured at the time of option presentation during each choice trial of the affective memory preference test. | 24 hours after ketamine administration |
| Difference in pupil response to shapes learned after winning versus losing money. | Between groups comparison of pupil dilation in response to shapes learned after a loss and shapes learned after a win in Wheel of Fortune draw that induces experimental change in negative/positive affect. | 24 hours after ketamine administration |
| Amount of money earned in the learning and memory task. | Between groups comparison of the total amount of money earned during the learning and memory task. | Final component completed 24 hours after ketamine administration before scanning |
| Change in bio-behavioral measures of stress following laboratory induced stress administered. | Between groups comparison of salivary cortisol in response to Oxford Cognition Stress Task. | 1-week after ketamine infusion |
| Change in bio-behavioral measures of stress following laboratory induced stress administered. | Between groups comparison of salivary alpha amylase in response to Oxford Cognition Stress Task. | 1-week after ketamine infusion |
| Change in bio-behavioral measures of stress following laboratory induced stress administered. | Between groups comparison of heart rate in response to Oxford Cognition Stress Task. | 1-week after ketamine infusion |
| Change in bio-behavioral measures of stress following laboratory induced stress administered. | Between groups comparison of visual analogue scale ratings in response to Oxford Cognition Stress Task. | 1-week after ketamine infusion |
| Recognition of positive and negative facial expressions. | Recognition accuracy for positive and negative facial expressions | Immediately and 24 hours after ketamine infusion |
| Recognition of positive and negative facial expressions. | Reaction time to recognise positive and negative facial expressions | Immediately and 24 hours after ketamine infusion |
| Categorisation of emotional words. | Accuracy of categorisation for positive and negative descriptor words. | 24 hours after ketamine infusion |
| Recognition of emotional words. | Reaction time to categorise positive and negative descriptor words. | 24 hours after ketamine infusion |
| Recall of emotional words. | Number of words correctly (hits) and incorrectly (false alarms) recalled. | 24 hours after ketamine infusion |
| D001523 |
| Mental Disorders |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |