The Effect of Plasma Osmolality on Brain Glutamate

This study is designed to test the hypothesis that plasma osmolality is linked with cortical glutamate concentrations in the brain. It also investigates whether the glutamate response in schizophrenia is enhanced compared to healthy controls.


Eligibility Criteria:
Inclusion criteria for healthy controls

1. Ages of 21-45 years from all ethnic backgrounds.
2. Male or female.
3. Written informed consent.
4. Female subjects will be studied during the follicular phase of their menstrual cycle.\*

Exclusion criteria for healthy controls

1. DSM-IV diagnosis of psychotic, anxiety, mood disorder.
2. A history of significant medical/neurological disease. Unstable medical condition based on EKG, vital signs, physical examination and laboratory work-up (CBC with differential, SMA-7, LFTs, TFTs, UA, Utox, Urine pregnancy test, folic acid, B12 levels).
3. History of allergies to drugs such as sulfa, multiple adverse drug reactions or known allergy to furosemide.
4. Any medication that in the opinion of the PI could interfere with either the safety of the study and/or the outcome measures, such as over the counter cough suppressants or antihistamines.
5. History of major psychiatric disorder in first-degree relatives.
6. Current substance abuse/dependency determined by plasma and urine toxicology.
7. Current treatment with medications with psychotropic effects.
8. Current pregnancy, unsatisfactory birth control method report for females.
9. Education \< 12th grade.
10. Non-English speaking.

Inclusion criteria for patients with schizophrenia

1. Ages of 21-45 years from all ethnic backgrounds.
2. Male or female.
3. Written informed consent.
4. DSM-IV diagnosis of schizophrenia or schizoaffective disorder.
5. For treated patients: The patient has been on a stable dose of medications (antipsychotics, antidepressants) for the past month and does not require a change of medications or dose adjustment at study entry.
6. For untreated patients: Has refused to be treated with medications, maintains regular clinic appointments with the clinicians, and does not pose an imminent danger to himself or others.
7. Female subjects will be studied during the follicular phase of their menstrual cycle\*.

Exclusion criteria for patients with schizophrenia

1. A history of significant medical/neurological disease. Unstable medical condition based on EKG, vital signs, physical examination and laboratory work-up (CBC with differential, SMA-7, LFTs, TFTs, UA, Utox, Urine pregnancy test, folic acid, B12 levels).
2. Orthostatic systolic blood pressure change\>20 mmHg or orthostatic pulse change\>20 bpm.
3. History of polydipsia/hyponatremia\*\*.
4. History of allergies to drugs such as sulfa, multiple adverse drug reactions or known allergy to furosemide.
5. Any medication that in the opinion of the PI could interfere with either the safety of the study and/or the outcome measures, such as over the counter cough suppressants or antihistamines.
6. Current use of lithium (lithium directly interferes with electrolyte balance).
7. Currently on clozapine as clozapine may interfere with brain water regulation (Leadbetter and Shutty, 1994).
8. Current substance abuse/dependency determined by plasma and urine toxicology.
9. Current treatment with benzodiazepines or mood stabilizers (these medications can alter glutamate transmission).
10. Current pregnancy, unsatisfactory birth control method report for females.
11. IQ \< 70 as determined by Wechsler Abbreviated Scale of Intelligence.
12. Non-English speaking