CRT-Guanfacine for SPD

This is a study to assess the efficacy augmenting cognitive remediation therapy (CRT) with a pharmacological agent for individuals with schizotypal personality disorder (SPD). Impaired cognition, along with functional and social skill deficits, is a core feature of schizophrenia and schizophrenia spectrum disorders. A better understanding of the cognitive and functional impairments in schizophrenia-related conditions, as well as the identification of interventions that can reduce these impairments, are vital to improving outcomes for individual with these disorders.

This study proposes to 1) evaluate the effects of 7.5 weeks of twice weekly cognitive remediation sessions, combined with concurrent administration of 8 weeks of guanfacine/placebo, on performance on cognitive, functional, and social skills performance measures in a sample of SPD patients with proven deficits in these areas. 2) Compare the effect of cognitive remediation therapy + 8 weeks guanfacine with cognitive remediation therapy + placebo on cognition in this schizophrenia spectrum disorder population. 3) Further characterize cognitive impairment in SPD using specific tests of working memory to evaluate the relationship between working memory and functional and social skill outcomes in this population.

The study hypothesizes that:

1. While both groups (those receiving CRT + guanfacine or CRT +placebo) will demonstrate improvements in overall cognitive functioning, SPD participants receiving CRT + guanfacine will evidence greater increases in post-treatment performance on our primary outcome measures-MATRICS battery total score, AX-CPT, N-Back, PASAT and DOT Test- particularly in areas related to working memory.
2. Participants receiving CRT + guanfacine will also demonstrate greater improvements in functional and social functioning exploratory measures, as evidenced by performance on our secondary assessments, the UPSA, SSPA, MASC, and Reading of the Mind in the Eyes.

Eligibility Criteria:
Inclusion Criteria:

* Willing and having capacity to provide informed consent
* Currently meeting DSM-IV-TR criteria for Schizotypal Personality Disorder
* Males and females between the ages of 18-65
* Medically healthy: no major or partially treated medical condition that, based on the judgment of the clinician, would either put the patient at increased risk and/or affect our findings.
* Neurologically healthy: no brain injury or head trauma associated with loss of consciousness, seizures, or other conditions that may have caused functional impairment.
* At least two weeks free of medication while participating in this study
* Score at least one standard deviation below normative means on at least one test in the cognitive battery.
* At least 2 weeks free of psychotropic medication while participating in this study. Medication such as NSAIDS (e.g. Advil), Tylenol, Levothyroxine (if on stable dose 1 month, no symptoms of hypothyroidism and normal thyroid labs), non-centrally acting antihistamines, H2 blockers (e.g. Zantac), PPIs (e.g. Prilosec, Prevacid), and others that do not impact cognitive functioning will be allowed; the study physician will evaluate any medication at the time of the medical clearance on a case by case basis.

Exclusion Criteria:

* Meet criteria for bipolar I disorder, schizophrenia, schizoaffective disorder, or any other psychotic disorder Clinically significant cardiovascular or neurological conditions, uncontrolled hypertension, clinically significant EKG abnormalities, or serious general medial illness
* Current substance abuse or have met criteria for substance dependence within the last 6 months (excluding nicotine)
* Currently meeting DSM-IV-TR criteria for Major Depressive Disorder, not better accounted for and secondary to a personality disorder
* Currently taking psychotropic medications
* Currently taking any medications (systemic or otherwise) that the study physician determines could interfere with the study medication and put the participant at risk and/or interfere with the data
* Currently pregnant or lactating
* Non-English speaking