The Effect of Nitric Oxide on Spatial Working Memory in Patients With Schizophrenia - Pilot Study

Study Overview
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Brief Summary
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Spatial working memory (ability to remember where objects are in space) is impaired in patients with schizophrenia. It is thought that this impairment occurs due to problems with the chemical messenger (neurotransmitter), glutamate, and the N-methyl-D-aspartate (NMDA) glutamate receptor, particularly in the hippocampal brain region. NMDA receptor activation leads to increases in the release of the second messenger Nitric Oxide. Impaired NMDA receptor function would therefore be predicted to lead to reductions in Nitric Oxide production. Recent work suggests that a drug, sodium nitroprusside, which releases nitric oxide, enhances some aspects of cognition in schizophrenia (specifically related to negative symptoms). In this study, the investigators will test the hypothesis that sodium nitroprusside improves spatial working memory in patients with schizophrenia. 15 patients will receive sodium nitroprusside, and 15 will receive a nonactive compound (placebo). Their performance on a spatial working memory task will be tested before and after administration of sodium nitroprusside or placebo.

Official Title
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The Effect of Nitric Oxide on Spatial Working Memory in Patients With Schizophrenia - Pilot Study

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Sodium Nitroprusside infusion
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a diagnosis of schizophrenia or schizoaffective disorder, currently experiencing an exacerbation of symptoms (a score > 20 for PANSS-Positive subscale), currently taking antipsychotics and who have given informed consent to participate. Exclusion Criteria: History of hypertension or current resting systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg. Relevant medical illness (renal, hepatic, cardiac), prior history of intolerance to sodium nitroprusside, presence of a seizure disorder, any change in psychotropic medication in previous 6 weeks, diagnosis of substance abuse, pregnancy (as determined by urine test) or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Glucose infusion<br>Placebo infusion of sterile 5% glucose - 500ml infused over 4 hours. | Other: Placebo<br> <br> |
| Active Comparator: Sodium Nitroprusside infusion<br>Sodium nitroprusside dissolved in 5% glucose solution. Infused at 0.5mcg/kg/min for 4 hours. | Drug: Sodium Nitroprusside infusion<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spatial Working Memory | performance on Cambridge Neuropsychological Test Automated Battery spatial working memory task | 4 hours post-infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Syndrome Scale (PANSS) | Symptoms rated on PANSS | 4 hours post-infusion | 
| Brief Psychiatric Rating Scale (BPRS) | Symptoms rated on BPRS | 4 hours post-infusion | 
| Quick Inventory of Depressive Symptomatology (QIDS) | Symptoms rated on QIDS | 4 hours post-infusion | 
| Hypomania Checklist (HCL-32) | Rating of symptoms on HCL-32 | 4 hours post-infusion | 
| Blood pressure | Measurement of blood pressure. | 4 hours post-infusion | 
| Heart rate | Heart rate change from baseline | 4 hours post-infusion | 
| Respiratory rate | change in respiratory rate from baseline. | 4 hours post-infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nitric Oxide, Sodium Nitroprusside, Spatial Working Memory, Psychosis, Schizophrenia