Relation of Catechol-O-methyltransferase (COMT) Genotype and Response to Cognitive Remediation Schizophrenia

Study Overview
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Brief Summary
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This project will explore the relationship between catechol-O-methyltransferase (COMT) Val158/108Met genotype and response to a 12-week computerized neurocognitive rehabilitation (CRT) given to chronic schizophrenic patients.

Detailed Description
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Cognitive deficits play a crucial role in both the pathogenesis and prognosis of schizophrenia. The COMT gene is functionally expressed in neural systems considered important in a range of healthy brain functions and brain disorders, including schizophrenia. The COMT Met allele has been shown to be associated with a lower activity form of COMT, and with better performance on neurocognitive tests, while the COMT Val allele is associated with poorer executive cognition. This study will investigate the relationship of COMT polymorphism in patients with chronic schizophrenia with the response to CRT targeting visuospatial processing, attention, and cognitive flexibility using MATRICS Consensus Cognitive Battery (MCCB) developed by the NIH-MATRICS initiative.

Official Title
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COMT Genotype and Response to Cognitive Remediation in Schizophrenia

Conditions
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Chronic Schizophrenia

Intervention / Treatment
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* Behavioral: Cognitive remediation therapy
* Genetic: COMT Genotyping


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participation in the active arm of the neurocognitive remediation program Age 18 - 55 Inpatients DSM-IV diagnosis of schizophrenia (all subtypes) with illness duration >5 years Auditory and visual acuity adequate to complete cognitive tests Stable dose of oral atypical antipsychotic for at least 4 weeks Total PANSS score > 60 RBANS total score ≤ 80 MMSE score of greater than or equal to 24 Good physical health determined by physical examination, laboratory tests Capacity and willingness to give written informed consent Exclusion Criteria: Inability to read or speak English Documented disease of the central nervous system History of intellectual impairment pre-dating onset of symptoms of psychosis (e.g. mental retardation) Clinically significant or unstable cardiovascular, renal, hepatic, gastrointestinal, pulmonary or hematologic conditions HIV + Patients diagnosed with substance dependence Currently participating in another experimental study, except for the parent study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: CRT Group<br> | Behavioral: Cognitive remediation therapy<br>* 36 sessions of Computerized Cognitive Skills Training, 3 per week for 12 weeks.<br>* Other names: educational and behavioral training techniques;Genetic: COMT Genotyping<br>* One time saliva sample is taken to genotype catechol-O-methyltransferase Val158/108Met alleles.<br>* Other names: 22q11.21-q11.23;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of the association of COMT Val108/158 Met genotype with the response to a computerized neurocognitive rehabilitation treatment in patients with chronic schizophrenia. |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To expand the response to a computerized neurocognitive rehabilitation treatment in patients with chronic schizophrenia to other haplotypes or identified genes. |  | 12 weeks | 
| To assess the differences in demographic variables (e.g. ethnicity, intellectual functioning as measured by WRAT III Reading test, and age) with response to computerized neurocognitive rehabilitation treatment in patients with chronic schizophrenia. |  | 12 weeks | 
| To assess the differences between antipsychotic treatment and response to computerized neurocognitive rehabilitation treatment in patients with chronic schizophrenia. |  | 12 weeks |