Cognitive Performance in Schizophrenia and Schizotypal Personality Disorder: The Influence of COMT and BDNF Polymorphisms Public

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

About this Dissertation

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School	Laney Graduate School
Department	Psychology
Subfield / Discipline	Clinical Psychology
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Psychology, Clinical
Mot-clé	schizophrenia, schizotypal personality disorder, COMT, BDNF
Committee Chair / Thesis Advisor	Walker, Elaine, Emory University
Committee Members	Neill, Darryl B, Emory University Compton, Michael T, Emory University Brennan, Patricia, Emory University Waldman, Irwin, Emory University Cubells, Joseph, Emory University

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