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INTRODUCTION
1. The necessity of this study
Schizophrenia is a group of severe psychosis, characterized by
psychotic symptoms such as delusions, hallucinations, catatonia,
disorganized speech and behavior. The symptoms of schizophrenia are
varied and they always change over time [1].
In the world, there are tens of millions of people with
schizophrenia, accounting for about 1% of the world's population.
Every year, this rate increases by 0.15% of the population. Prevalence
of schizophrenia in Vietnam is 0.3-0.8%, and every year it increases by
0.1-0.15% of the population[2].
For decades, many authors have focused on the etiology and
pathogenesis of schizophrenia according to several trends such as genetics
[9], [10]...neurotransmitters [21], [22]...environmental factors [19],
[20]...Each schizophrenia theory is characterized by its advantages and
limitations.
Although many studies on schizophrenia have been conducted in
Vietnam, most of them have just described the clinical symptoms,
progression and treatment of schizophrenia. Few studies have researched
on EEG, but they still restricted, especially about the feature of EEG in
schizophrenia. Many studies of molecular, genetic and gene change in
schizophrenia in the world [1], [2] have concerned of gene Catechol-O-
methyltransferase and Zinc-finger protein 804A) [13], [14], but number of
studies on nucleotide polymorphisms in schizophrenia has been limited in
Vietnam.
In previous decades, studies on the etiology and pathogenesis of
schizophrenia, including EEG and schizophrenic genetic, have faced many
difficulties and hassles, both in terms of technical procedures and
equipment, which are not suitable to the current situation in Vietnam.
Nowadays, because of new techniques and methods in quantitative
electroencephalography [49], [50] and new generation sequencing [15], in-
depth studies of EEG and molecular genetic in schizophrenia become
available. Therefore, the “Research on features of electroencephalogram
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and some polymorphisms of COMT, ZNF804A gene in patients with
schizophrenia” has been launched with two objectives as follows:
1/ To describe EEG and relationship between EEG and clinical
features in patients with schizophrenia.
2/ To assess the frequency of allele and genotypic distribution of
ZNF804A gene polymorphism rs1344706 and COMT gene
polymorphism rs165599 in patients with schizophrenia.
2. Practical significance and new contributions
- This has been the first systematic study on clinical features
which initially assessed on the EEG and ZNF804A gene rs1344706
polymorphism, COMT gene polymorphism rs165599 in patients with
schizophrenia in Vietnam.
- The analysis of EEG was successfully applied by EEGLab sofware
running on Matlab in schizophrenic patients.
- EEG changes in patients with schizophrenia were varied:
Amplitude of alpha wave, delta wave and theta wave had statistically
significant differences between two groups and recording channels. The
energy property of alpha wave in schizophrenia group was significantly
lower than in control group. The energy property of delta wave and theta
wave in schizophrenia group were significantly higher than in control
group. EEG frequency did not change in schizophrenic patients, comparing
to control group. There was a correlation between hallucinations and EEG
in patients with schizophrenia, including: increase of amplitude, energy
properties of alpha, delta, and theta waves.
- The frequency of allele rs1344706 polymorphism in schizophrenic
patients was 53.30% (A) and 46.70% (C), and the distribution of three
genotypes AA, CC and AC in patients with schizophrenia was 28.19%,
21.59% and 50.22%. Whereas, frequency of allele A and G of rs165599
polymorphism in schizophrenia patients was 51.32% and 48.68%; and the
distribution of genotypes AA, GG and AG were 22.75%, 25.11% and
47.14%, respectively. There was no difference in allele frequency and
genotypic distribution of rs1344706 and rs165599 polymorphism between
schizophrenia and control group. There was also no difference in allele
frequency and genotypic distribution between two groups in both females
and males.
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- This research opened a new direction for early diagnosis as well as
tools to support the diagnosis and evaluation of treatment results in
patients with schizophrenia.
3. Structure of thesis
Thesis was written in 152 pages, tables and figures. The content
includes: Introduction (2 pages); Chapter 1: Over view (38 pages);
Chapter 2: Objects and methods (18 pages); Chapter 3: Result (46 pages);
Chapter 4: Discussion (26 pages) and conclusion (2 pages);
Recommendation (1 page); List of research projects that publish results of the
thesis page; References (18 page) (Vietnamese documents and foreign
languages documents).
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CHAPTER 1
OVERVIEW
1.1 Concept of schizophrenia
Schizophrenia is characterized by many disturbances such as
thinking disorder, emotional and behavioral disorder. These symptoms
include: positive symptoms such as delusions, hallucinations, and
catatonia; negative symptoms such as: flat affect, asociality, avolition,
anhedonia, and alogia [5].
1.2. Electroencephalogram in schizophrenia
Previous studies have shown the changes of alpha wave, delta wave
and theta wave in schizophrenia in terms of amplitude, power, frequency,
and reactivity. Especially, there are the appearance of waves with
frequency 25-35 Hz and low amplitude, as called "choppy". EEG changes
in schizophrenia occur in 64% of patients.
Nowadays, researches have been focusing on analyzing the EEG in
schizophrenia in terms of energy and output property.
1.3. Changes in ZNF804A and COMT gene, in schizophrenia
1.3.1. ZNF804A gene and schizophrenia
ZNF804 is a gene encoding the ZNF804A protein in humans,
located on chromosome 2 q32.1, consisting of 4 exons, encoding
proteins with 1210 amino acids. In humans, ZNF804A is widely
expressed in the brain, particularly in the developing hippocampus
and cortex, as well as the cerebellum in adults. A study of GWAS
identified ZNF804A as a sensitive gene of schizophrenia. From the
genealogical studies of schizophrenia, it is said that genetic
coefficient is nearly 80%. The rs1344706 polymorphism in intron 2 of
the ZNF804A gene has been identified as the single polymorphism
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which is most closely associated with schizophrenia. Recent evidences
also have shown that the ZNF804A gene may be one of the most
potential genes which relate in schizophrenia [1].
1.3.2. The rs1344706 Polymorphism and schizophrenia
The relationship between rs1344706 polymorphism and
schizophrenia is widely recognized and reached a consensus [85]. The
association between ZNF804A and schizophrenia, especially rs1344706
polymorphism, has been confirmed by many researches on European
samples. However, these results have not been consistent among Asians
[86].
1.3.3. COMT gene and schizophrenia
COMT gene has a schizophrenia-related region on chromosome 22;
contains important fragments 22q11.2; related to catecholamine
metabolism: group of neurotransmitters involved in mental disorders and
psychiatric treatment. Relationship of the COMT gene rs4680
polymorphism related to females in schizophrenia was found in a study (p
= 0.02) [108], [109]. Another studies of COMT gene also showed the
relationship between schizophrenia and environmental risk factors such as
marijuana stimulant use to schizophrenia [110], [111], [112].
1.3.4. The rs165599 polymorphism and schizophrenia
The rs165599 polymorphism, which has received much attention
in schizophrenia researches, suggests it has a role to play. This
polymorphism, which plays a role in increasing dopamine, has explained
some of the features of schizophrenia, including delusions, hallucinations,
disorganized speech and behavior. This role is also shown in the
association of alleles with schizophrenia at the age of onset and the
decrease in working productivity [116].
1.4. Research on Electroencephalogram and genes in schizophrenia in
Vietnam
Schizophrenia is one of the leading causes of disability, often onset
at a young age, with severe consequences for patients, families and society.
In the world, researches on changing EEG and genetic features in
schizophrenia have been interested in many respects. However,
schizophrenia has been highly concerned about epidemiology and clinical
features in Vietnam. There have also been some studies evaluating EEG in