Inclusion Criteria:

Patients (n=10):

• All patients included in the study will have a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder. Outpatients with schizophrenia (DSM-IV 295.00, 295.10, 295.30, 295.60, 295.90) or schizoaffective disorder (DSM-IV 295.70) will be the primary source of subjects for this project, although inpatients that are being discharged will also be acceptable. All patients will be followed longitudinally.
• Patients who are from 18-65 years of age will be accepted.
• Patients will be screened for medical and psychiatric diagnoses.
• At the time of examination and testing, patients must be stable and taking either olanzapine 10 mg per day for at least two weeks, or at least 2 mg of risperidone per day for at least two weeks, or on risperidone Consta injections (at least 25 mg every two weeks) and not taking an anticholinergic medication for at least one week.
• While recruiting stable patients for this study, this does not necessarily mean free of side effects or free of symptoms of schizophrenia or schizoaffective disorder. Patients that express a desire to switch to aripiprazole may be having side effects, or may be worried that increasing the dose of their current medication may cause side effects.

Controls (n=10):

• The normal control group will provide images of normal response on the behavioral and functional measures, as well as control for the scan-rescan (learning, novelty) effects. They will be matched for age, sex, handedness, and level of education with the patients. They will be screened for medical and psychiatric diagnoses.

Exclusion Criteria:

Patients:

• Any comorbid major psychiatric diagnoses (major depressive disorder, obsessive-compulsive disorder, generalized anxiety disorder, panic disorder, any disorder with psychosis other than those used as inclusion criteria, bipolar disorder).
• Any significant or unstable medical disorder (including unstable or uncontrolled diabetes; long term, severe, or uncontrolled hypertension; or any neurological disorder). Clinical judgment will be used on a case-by-case basis. Special care will be taken in examining patients for metabolic disturbances such as hyperglycemia or hyperlipidemia, due to the increased risk of these problems related to the use of antipsychotics. Subjects with clinically unstable and markedly abnormal metabolic profiles will be excluded.
• Active alcohol or substance dependence.
• Significant alcohol or substance abuse in the past six weeks or alcohol or substance dependence in the past year (as defined by DSM-IV).
• Unable to speak, read and understand English, or if the study doctor thinks that the patient cannot follow the study procedures.
• Inability to understand the purpose of the study and give consent.
• Subject is hearing impaired.
• Subject is left-handed.
• Significant abnormalities on physical/neurological examination not consistent with an inclusive diagnosis.
• Current treatment with a classical antipsychotic medication.
• Current treatment with an anticholinergic medication.
• History of adverse response or previous lack of response to aripiprazole.
• Pregnant or lactating women.
• Women of childbearing potential not using medically accepted means of contraception (e.g., intrauterine device [IUD], birth control pills, barrier devices, implanted hormones).
• Handedness will be tracked, and left-handed patients will be excluded due to the small sample size and the variance this will add to cognitive testing.

Controls:

• Current treatment with any psychotropic or anticholinergic medication.
• Any major psychiatric diagnoses (major depressive disorder, obsessive-compulsive disorder, generalized anxiety disorder, panic disorder, any disorder with psychosis, bipolar disorder, attention-deficit/hyperactivity, learning or developmental disorder).
• Any significant medical disorder (including unstable or uncontrolled diabetes; long term, severe, or uncontrolled hypertension; or any neurological disorder). Clinical judgment will be used on a case-by-case basis.
• Any active alcohol or substance dependence in the past six weeks.
• Significant alcohol or substance abuse in the past six weeks, or alcohol or substance dependence in the past year (as defined by DSM-IV).
• Inability to understand the purpose of the study and give consent.
• Significant abnormalities on physical/neurological examination.
• Subject is hearing impaired.
• Subject is left-handed.
• Pregnant or lactating women.
• Women of childbearing potential not using medically accepted means of contraception (e.g., IUD, birth control pills, barrier devices, implanted hormones).

• Dropout criteria: subjects that begin the study and are not able to finish the study will be tracked. Ongoing criteria for termination from the study will include:

  • Adverse events that are intolerable to the patient that prevent continued involvement in the study.
  • New onset medical disorder of such significance as to prohibit further involvement.
  • New onset major psychiatric disorder.
  • Initiation or recurrence of alcohol or substance abuse/dependence.
  • Subject withdraws consent for any reason.