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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Glucose infusion | Placebo Comparator | Placebo infusion of sterile 5% glucose - 500ml infused over 4 hours. |
|
| Sodium Nitroprusside infusion | Active Comparator | Sodium nitroprusside dissolved in 5% glucose solution. Infused at 0.5mcg/kg/min for 4 hours. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sodium Nitroprusside infusion | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Spatial Working Memory | performance on Cambridge Neuropsychological Test Automated Battery spatial working memory task | 4 hours post-infusion |
| 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 |
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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.
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| Name | Affiliation | Role |
|---|---|---|
| James Stone, MBBS PhD | King's College London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Research Facility, King's College Hospital | London | SE5 | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27655012 | Derived | Stone JM, Morrison PD, Koychev I, Gao F, Reilly TJ, Kolanko M, Mohammadinasab A, Kapur S, McGuire PK. The effect of sodium nitroprusside on psychotic symptoms and spatial working memory in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial. Psychol Med. 2016 Dec;46(16):3443-3450. doi: 10.1017/S0033291716002245. Epub 2016 Sep 22. |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D011618 | Psychotic Disorders |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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|
| 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 |