Cognitive Performance in Schizophrenia and Schizotypal Personality Disorder: The Influence of COMT and BDNF Polymorphisms Público
Trotman, Hanan D. (2010)
Abstract
Abstract
The relation of the Catechol-O-Methyltransferase
Val108/158Met ( COMT,
rs4680) and Brain-Derived Neurotrophic Factor BDNF
Val66Met ( BDNF, rs6265)
polymorphisms with dopamine neurocircuitry and brain functions make
them strong
candidates for investigating the association between genes and
cognitive function.
Further, both of these polymorphisms have been implicated in risk
for psychotic
disorders, as well as cognitive impairment in psychosis.
Nonetheless, findings on the
association of these genes with cognition are mixed. Although the
cumulative findings
provide no consistent evidence to support an association of
COMT or BDNF with
vulnerability to psychosis, or of COMT with cognition,
recent studies suggest an
interactive effect of COMT and BDNF on cognitive
performance. Based on these
findings, the present study examined both the main and interactive
effects of COMT and
BDNF on cognition in schizophrenia-spectrum patients
(patients diagnosed with
psychosis or schizotypal personality disorder) and controls. The
Logical Memory I and II
and Letter-number Sequence subtests of the Wechsler Memory Scale,
3rd Edition (WMS-
III) were administered. There was no main or interactive effect of
the two
polymorphisms on cognition within the schizophrenia-spectrum
sample. Exploratory
analyses revealed significant sex-specific effects; however, these
were based on small
subsamples, and should be interpreted with caution. Limitations of
the present study,
most notably the low frequency of BDNF Met carriers,
constrained statistical power for
detecting effects. The present findings highlight the complex
nature of genetic effects on
cognition.
Table of Contents
TABLE OF CONTENTS
INTRODUCTION……………………………………………………………………….1
Schizophrenia: Phenomenology and Hypothesized
Etiology…………………………4
Schizotypal Personality
Disorder……………………………………….......................9
Cognitive Impairment in the Schizophrenia
Spectrum…………………......................10
Genetic Vulnerability and
Cognition………………………………………………….16
Genetic Mechanisms in Schizophrenia Spectrum
Disorders………………………….18
Phenotypic Heterogeneity and the Endophenotype Approach
………….....................21
Catechol-O-Methyltransferase (COMT)
Val108/158Met………………………….....24
Brain-Derived Neurotrophic Factor (BDNF) Val66Met
……………………………..30
Epistatic Effects and Cognitive
function……………………………………………...33
Goals of the Present
Study…………………………………………………………….37
METHODS……………………………………………………………………………….38
Sample………………………………………………………………………………...38
Verbal Memory
Tasks………………………………………………………………...40
Procedures
…………………………………………………………………………….41
RESULTS………………………………………………………………………………...44
Data
Analyses…………………………………………………………………………44
Preliminary Analyses of
Distributions………………………………………………...46
Test of Potential
Covariates…………………………………………………………...47
Diagnostic Group Differences in
Performance………………………………………49
Quality Control Analyses for
Genotyping…………………………………………….51
Genotype
Frequencies…………………………………………………………………51
The Relations of Genotype with
Performance………………………………………...52
DISCUSSION…………………………………………………………………………….57
Relation of COMT with Verbal Memory
Performance……………………………….58
Relation of BDNF with Verbal Memory
Performance……………………………….59
Additive and Interactive
Effects……………………………………...........................60
Secondary Analyses of Sex Effects on Verbal Memory
Performance………………..61
Genetic Factors related to Null
Findings……………………………………………...62
Clinical Factors related to Null
Findings……………………………………………...63
Current Study
Limitations…………………………………………………………….63
Future
Directions……………………………………………………………………...65
Clinical
Implications…………………………………………………………………..67
Concluding
Thoughts………………………………………………………………….68
REFERENCES…………………………………………………………………………...
69-112
TABLES………………………………………………………………………………….113-129
FIGURES…………………………………………………………………………………
131-142
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