The Relationship between Dopamine Beta Hydroxylase Polymorphisms and Attenuated Psychotic Symptoms in Putatively Prodromal Adolescents 公开

Ko, Chanyoung (2011)

Permanent URL: https://etd.library.emory.edu/concern/etds/8w32r647k?locale=zh
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Abstract

Abstract


Elevated dopamine in the subcortical regions of the brain such as the striatum is strongly
associated with vulnerability to psychotic symptoms. The neural mechanisms of elevated
subcortical dopamine remain ambiguous. Dysregulation of dopamine beta hydroxylase (DBH) is
one possible contributor to abnormal dopamine levels. One functional single nucleotide
polymorphism (SNP) at the DBH gene, -1021C->T, has shown to affect DBH enzyme activity in
plasma and cerebrospinal fluid (CSF). The TT genotype of -1021C->T, in particular, has been
associated with low DBH enzyme activity. Previous studies suggest that lower DBH activity
may contribute to elevated DA levels, which in turn may increase the vulnerability for
developing psychotic symptoms. Participants were administered the Scale for Prodromal
Symptoms (SOPS) as a measure of prodromal symptom severity. Each participant also provided
a saliva sample for DNA extraction. On all four SOPS prodromal symptom scores, there was no
significant difference between individuals who are homozygous C and T allele carriers at -
1021C->T. Furthermore, there were no significant differences among the three genotypes (CC,
CT, and TT) in severity of prodromal symptoms. Though not reaching statistical significance,
"T carriers" and TT genotype prodromal individuals showed a trend toward greater positive
symptom severity compared to the CC genotype adolescents. Such findings that individuals with
the DBH SNP associated with low DBH levels have greater vulnerability for developing
psychotic symptoms are consistent with previous literature. Current findings did not reach
statistical significance, suggesting that the present sample size was not sufficient to detect effects
of the DBH SNP -1021C->T alone on prodromal symptoms in adolescents at high-risk for
developing psychosis. It is likely that the young age of the sample at follow-up contributed to
the lower conversion rate.

Table of Contents

TABLE OF CONTENTS
INTRODUCTION (1)
Schizophrenia: Phenomenology and Hypothesized Etiology (2)

The Psychosis Prodrome (7)

Dopamine Beta Hydroxylase (8)

CURRENT STUDY (14)
METHOD (15)
Participants (15)
Procedures (17)
Clinical Measures (17)
DNA Collection and Extraction (19)
RESULTS (20)
Symptom Severity by Diagnostic Groups (23)
Symptom Severity by Genotype (T carrier vs. homozygous C) (24)
Conversion Status by Genotype (T carrier vs. homozygous C) (25)
DISCUSSION (26)

REFERENCES (32)
TABLES (39)
FIGURES (48)

LIST OF TABLES
1 Clinical and Demographic Characteristics (39)
2 Clinical and Demographic Characteristics (1021C/T Genotypes) (40)
3 Clinical and Demographic Characteristics (Homozygous C and T carriers) (41)
4 Genotype Frequencies (1021C/T) in the Sample (42)
5 Genotype Frequencies by Diagnostic Groups (43)
6 Conversion Diagnoses by Diagnostic Groups (44)
7 Conversion Diagnoses by Genotype (Collapsed) (45)
8 Conversion Diagnoses by Genotype (Not collapsed) (46)

LIST OF FIGURES
1 Mean positive symptoms by DBH SNP groups (CC vs. T Carrier) (48)
2 Mean negative symptoms by DBH SNP groups (CC vs. T Carrier) (49)
3 Mean disorganized symptoms by DBH SNP groups (CC vs. T Carrier)(50)
4 Mean general symptoms by DBH SNP groups (CC vs. T Carrier) (51)
5 Conversion diagnoses by DBH SNP groups (CC vs. T Carrier) (52)
6 Conversion diagnoses by DBH SNP genotypes (CC vs. CT vs. TT) (53)
7 Mean positive symptoms by DBH SNP genotypes (54)
8 Mean negative symptoms by DBH SNP genotypes (55)
9 Mean disorganized symptoms by DBH SNP genotypes (56)
10 Mean general symptoms by DBH SNP genotypes (57)

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