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

• To expand the response to a computerized neurocognitive rehabilitation treatment in patients with chronic schizophrenia to other haplotypes or identified genes. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• 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. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• To assess the differences between antipsychotic treatment and response to computerized neurocognitive rehabilitation treatment in patients with chronic schizophrenia. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

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.

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.

• Behavioral: Cognitive remediation therapy
  36 sessions of Computerized Cognitive Skills Training, 3 per week for 12 weeks.
  Other Name: educational and behavioral training techniques
• Genetic: COMT Genotyping
  One time saliva sample is taken to genotype catechol-O-methyltransferase Val158/108Met alleles.
  Other Names:

  • COMT polymorphism
  • 22q11.21-q11.23

• Woodward ND, Jayathilake K, Meltzer HY. COMT val108/158met genotype, cognitive function, and cognitive improvement with clozapine in schizophrenia. Schizophr Res. 2007 Feb;90(1-3):86-96. Epub 2006 Nov 22.
• Bosia M, Bechi M, Marino E, Anselmetti S, Poletti S, Cocchi F, Smeraldi E, Cavallaro R. Influence of catechol-O-methyltransferase Val158Met polymorphism on neuropsychological and functional outcomes of classical rehabilitation and cognitive remediation in schizophrenia. Neurosci Lett. 2007 May 7;417(3):271-4. Epub 2007 Mar 2.

Inclusion Criteria:

1. Participation in the active arm of the neurocognitive remediation program
2. Age 18 - 55
3. Inpatients
4. DSM-IV diagnosis of schizophrenia (all subtypes) with illness duration >5 years
5. Auditory and visual acuity adequate to complete cognitive tests
6. Stable dose of oral atypical antipsychotic for at least 4 weeks
7. Total PANSS score > 60
8. RBANS total score ≤ 80
9. MMSE score of greater than or equal to 24
10. Good physical health determined by physical examination, laboratory tests
11. Capacity and willingness to give written informed consent

Exclusion Criteria:

1. Inability to read or speak English
2. Documented disease of the central nervous system
3. History of intellectual impairment pre-dating onset of symptoms of psychosis (e.g. mental retardation)
4. Clinically significant or unstable cardiovascular, renal, hepatic, gastrointestinal, pulmonary or hematologic conditions
5. HIV +
6. Patients diagnosed with substance dependence
7. Currently participating in another experimental study, except for the parent study.

• National Institute of Mental Health (NIMH)
• Albert Einstein College of Medicine of Yeshiva University