Schizophrenia is a serious, often disabling and recurrent mental illness. Previously, the prognosis of patients with schizophrenia was thought to be poor and the disease associated with an inexorably progressive course. However, studies of first episode patients early in the course of illness have demonstrated their superior treatment response in comparison to chronic multi-episode patients. Moreover, there is a growing awareness that first episode patients may in some cases achieve symptomatic remission and good outcomes with proper treatment. One particularly important variable impacting outcome seems to be the duration from first episode to first relapse, with longer durations being associated with better clinical outcome.

We are seeking volunteers who are having their first psychotic episode. Participation in the study involves 8 weekly outpatient visits over two months, and includes FDA-approved antipsychotic medications and study-related examinations and health assessments. At the completion of the 8 weeks, there is an opportunity for extended treatment for 18 months.

Volunteers must:
• Be age 16 to 30, male or female
• Meets DSM-IV criteria for schizophreniform disorder, schizophrenia, psychosis NOS, or schizoaffective disorder with active psychotic symptoms at least one month, and not more than 12 months.
• Be either an inpatient or clinically stable enough to be treated in an outpatient setting and able to cooperate with examinations every week
• Has no previous history of significant (greater than a total of 4 weeks of treatment) pharmacological treatment with an antipsychotic medication
• Able to fully participate in the informed consent process, or have a legal guardian able to participate in the informed consent process.

Volunteers must not:
• Be pregnant, or planning a pregnancy
• Have any current substance use
• Have a history of mental retardation
• Be at serious risk for suicide

One of the primary needs of any human being is the maintenance of a constant fluid balance that is proportionate to levels of sodium and potassium. All living cells depend directly on water for metabolic processing, and the precise regulation of water balance both inside of cells (the intracellular compartment) and outside of cells (the extracellular compartment) involves a vast and complex process. Water is continuously being excreted and secreted through the processes of waste removal, breathing, and temperature regulation. Nevertheless, humans normally manage to take in sufficient fluid to maintain the correct balance between water and electrolyte levels within surprisingly narrow limits. In some medical situations the balance of sodium becomes abnormally low (this is called "hyponatremia"). While hyponatremia has been found in about 2.5% of all hospitalized patients, there is a nearly three-fold increase in hyponatremia among residents in long-term psychiatric institutions.

We are seeking volunteers with psychotic disorders who have low levels of sodium in their blood. The primary aim of this project is to examine the efficacy of a new drug called Tolvaptan in the treatment of hyponatremia. Participation in the study involves a 1-month commitment with regular outpatient visits, and study-related medications, examinations, and health assessments. At the completion of the 1-month study, there is an opportunity for extended treatment for two years.

Volunteers must:
• Be over 18 years of age
• Have a serum sodium level of <134 mmol/L
• Not have active polydipsia
• Be able to fully participate in the informed consent process, or have a legal guardian able to participate in the informed consent process

Volunteers must not:
• Have specific medical conditions that will be reviewed with each individual
• Be at serious risk for suicide
With a few exceptions, patients will remain on their current medication regimen.

Importantly, an open-label extension study is available for at least one year following completion of the double-blind study.