Guanfacine Adjunctive Treatment to Atypical Antipsychotics for Cognitive Dysfunction in Schizophrenia

Inclusion Criteria:

1. Subjects will be males and females between the ages of 18 and 55.

2. In good general medical health.

3. Have a DSMIV diagnosis of schizophrenia, any subtype, or schizoaffective disorder.

4. Patients who have been diagnosed with other DSMIV Axis I disorders may be included,unless they are actively using illicit substances.

5. Receiving treatment with aripiprazole, olanzapine, quetiapine, and/or risperidone astheir antipsychotic medication

6. Subjects will demonstrate significant memory impairment by performing at least twostandard deviations below normal performance on the California Verbal Learning Test (CVLT). Using subjects with a clear impairment in acquisition and recall will avoid aceiling effect in this measure.

7. Subjects will also be required to have at least an 8th grade reading level and/or afull-scale IQ of at least 85 as assessed by the Wide Range Achievement Test (WRAT).

8. Patients are allowed to be on the following anti-depressant medications: Fluoxetine (PROZAC), Sertraline (ZOLOFT), Paroxetine (PAXIL), Celexa (CITALOPRAM), Busprion (WELLBUTRIN), Venlafaxine (EFFEXOR), and Buspirone (BUSPAR).

Exclusion Criteria:

1. Have a recent history (within previous year) of serious suicide, homicide, or seriousphysical violence, or current suicidal or homicidal thoughts

2. Active use of illicit substances.

3. Meet DSM-IV criteria for a current episode of major depression or mania.

4. Have a history of severe head trauma, neurological disorder or medical illness whichmay contribute to the patient's psychiatric symptoms and cognitive impairment.

5. Have a medical illness which requires that they take any medication that has CNSactivity or which is known to interact with guanfacine (e.g barbiturates, apha-1antagonists, beta blockers).

6. Receive treatment with other concomitant neuroleptics in addition to risperidone orolanzapine.

7. Receive concomitant anticholinergic drugs, or. If the patient receivesbenzodiazepines, they must be short or intermediate acting (e.g. alprazolam,lorazepam) and they must be held 48 hours prior to cognitive testing. Treatment withmood stabilizers such as lithium and depakote will be allowed for this study. If thepatients is receiving treatment with lithium the level must be < 1 meq/l.

8. Are unable to give informed consent.

9. Have a history of developmental disorder or less than an eighth grade reading level.

10. Have a history of bowel obstruction or untreated benign prostatic hypertrophy. Aretaking antihypertensive medications of the class of beta-blockers, alpha-1antagonists, calcium channel blockers, or alpha-2 agonists.