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
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.
- 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
- 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.
- 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