Nghiên cứu đặc điểm điện não đồ và một số đa hình trên gen COMT, ZNF804A ở bệnh nhân tâm thần phân liệt tt tiếng anh

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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-Omethyltransferase 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
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.


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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.
- 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);


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Recommendation (1 page); List of research projects that publish results of
the thesis page; References (18 page) (Vietnamese documents and foreign
languages documents).

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,


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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 polymorph ism
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].


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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 schizophrenia, but these studies have just assessed through subjective
evaluation. Extensive and in-depth assessments of specific functional
areas related to high-level functional disorders as well as studies of
genetic and polymorphic traits, including ZNF804A and COMT gene in
Vietnamese, have been still unclear. Researches on EEG and genes in
schizophrenia in the world still have showed many different results.
Therefore, research on these issues in Vietnamese population is new and
necessary.

CHAPTER 2
OBJECT AND METHOD
2.1. Study objects
The schizophrenia group includes 230 patients with schizophrenia
diagnosed according to criteria of World Health Organization in 1992
(ICD-10F). These patients was treated at the Department of Psychiatry,
Military Hospital 103, Vietnamese Military Medical University.
The control group includes 94 healthy people who suitable for age,
gender and some other conditions with above patients.
2.2. Methods
2.2.1. Study design
A Cross-sectional follow-up study includes analysis of clinical

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symptoms of patients corresponding to COMT, ZNF804A gene and EEG
changes in the schizophrenia group.
2.2.2. Clinical research method
Clinical research method is to directly interview with patients and
their family members to collect information about the patient's history.
2.2.3. Electroencephalogram analysing method
EEGLab v13.4.4b analysis software running on MatLab 2017
software
Procedure of EEG analysis was conducted at Diagnostic Imaging
Department-103 Military Hospital-Vietnam Military Medical University.
2.2.4. Research method of genetic polymorphism
The ZNF804A gene polymorphism rs1433706 was determined by
the direct sequencing method and the COMT gene polymorphism
rs165599 was determined by the polymerase chain reaction-restriction
fragment length polymorphism (PCR-RFLP) method.
Process of conducting these techniques to determine the
polymorphisms: Military Pharmaceutical Research Centre-Vietnam
Military Medical University.


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Chapter 3
RESULTS
3.1. General features of study subjects
Table 3.1. Distributon by age group of two groups

< 20

Schizophrenic group
n (%)
25 (10.87)

Control group
n (%)
10 (10.64)

20-29

93 (40.43)

45 (47.87)

30-39

61 (26.52)

22 (23.40)

40-50

35 (15.22)

13 (13.83)

> 50

16 (6.96)

04 (4.26)

Mean age

31.24± 0.97

31.02±10.40

Age group

p

> 0.05

> 0.05

The result in Table 3.1 showed that there was the similarity about
the number and prevalence by age group of two groups (p>0.05). There
was a significant difference on distribution by age group between each
age range band in two groups (p<0.001), with the highest prevalence of
20-29 years old; number of cases were greatly massive at those of 20-39
years old. There was no significant difference on mean age between two
groups (Schizophrenic group: 31.24±10.97, Control group: 31.02±10.40,
p=0.87).
Sex

Bảng 3.2. Distribution by sex of two groups
Schizophrenic group
Control group

n (%)
n (%)

Male

156 (67.83)

57 (60.64)

Female

74 (32.17)

37 (39.36)

p
> 0.05

The result in the Table 3.2 showed that there was a similarity
between two groups (p>0.05). The result also illustrated that prevalence
was higher in subjects of male than those of female (p<0.001).


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3.2. Features of mental disorders in patients with schizophrenia
3.2.1. Personal and family history
Table 3.3. Distribution by personal history in patients with schizophrenia
p
Feature

Group
Number (n) Percent (%)
History of
obstetrics
Mental
development

Normal

227

98.69

Abnormal

3

1.31

Fast

91

39.57

Slow

139

60.43

<0.001

<0.001

The result in Table 3.3 shows that the prevalence of patients with a
normal obstetric history was higher than the prevalence of patients with
an abnormal obstetric history (p<0.001). While the prevalence of patients
with mental development was statistically lower than the prevalence of
patients with normal mental development (p<0.001).

Figure 3.1. Distribution by family history in patients with schizophrenia
The result in Figure 3.1 shows that the prevalence of patients
whose third-degree relative suffering from mental disorders was high,
accounting for 11.74%.
3.2.2. Hallucinations
Table 3.4. Frequency of hallucinations in patients with schizophrenia
Content of auditory
p
Number (n) Percent (%)
hallucinations
Comment
182
79.13
0.000
Inducement
76
33.04
Conversation
58

25.22
Command
14
6.09


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Echoing thought
10
4.35
The result in Table 3.4 shows that the auditory hallucination with
commenting content accounted for the largest prevalence (79.13%), while
content of conversation accounted for the lowest prevalence (25.22%).
Table 3.5. Number of types of hallucinations in patients with
schizophrenia
p
Content of hallucinations
Number (n)
Percent (%)
None of hallucination
One type of hallucination
Two types of hallucination
Three types of
hallucination

7
110
109

3.04
47.83
47.39

4

1.74

0.000

The results in Table 3.5 shows the number of hallucinations in
patients with schizophrenia. Patients experiencing one type of
hallucinations accounted for the highest prevalence (47.83%), followed
by patients experiencing two types of hallucinations (47.39%).
Table 3.6. Classification of the content of hallucinations in patients with
schizophrenia
Content of hallucinations
p
Number
Percent
(n)
(%)
Pseudo
135
74.18
Comment
0.000
True
47
25.82

Pseudo
59
77.63
Inducement
0.000
True
17
22.37
Pseudo
49
84.48
Conversation
0.000
True
9
15.52
Pseudo
9
64.29
Command
0.285
True
5
35.71
Pseudo
6
60
Echoing thought
0.754
True

4
40
The results in Table 3.6 shows that the prevalence of pseudohallucinations were higher true hallucinations, especially in content of
comment (74.18% compared to 25.82%), conversation (84.48% compared
to 15.52%), and inducement (77.63% compared to 22.37%).
Table 3.7. Behavioral control in patients with schizophrenia due to


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hallucinations
Behavioral control

Numbe

Percent

p

r (n)
(%)
Yes
49
26.92
0.000
No
133
73.08
33
43.42

auditory Yes
0.251
No
43
56.58
15
25.86
auditory Yes
0.000
No
43
74.14
10
71.43
auditory Yes
0.180
No
4
28.57
Yes
2
20
0.109
No
8
80
The results in Table 3.7 shows that the auditory hallucinations
usually control behaviors of patients, with significant differences in
comment auditory hallucination (26.92% compared to 73.08%) and
conversation auditory hallucination (25.86% compared to 74.14%)

(p<0.001). Thus, our results illustrated that prevalence of controlling
behavior of auditory hallucination was from 20% to 71.43%.
3.2.3. Delusions
Table 3.8. Frequency of delusions in patients with schizophrenia
p
Number
Percent
Type of delusions
(n)
(%)
Contact delusion
49
21.30
Persecutory delusion
200
86.96
Delusion of being followed
154
66.96
Broad casting thought
29
12.61
Controled delusion
26
11.30
< 0.000
Grandiose delusion
10
4.35
Bizzare delusion

6
2.61
Delusion of being sick
3
1.30
Invention delusion
1
0.43
Jealous delusion
1
0.43
The result in Table 3.8 shows the prevalence of types of delusions
in schizophrenia. Persecutory delusion accounted for the highest rate
with 86.96%. There was very few patients who experienced invention
Comment
hallucination
Inducement
hallucination
Conversation
hallucination
Command
hallucination
Echoing thought

auditory


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and jealous delusion (equally 0.43%).

Table 3.9. The number of types of delusions in patients with
schizophrenia
Number of types of delusions

Number

Percent

p

(n)
(%)
None of delusion
4
1.74
One type
33
14.35
0.000
Two types
136
59.13
At least 3 types
57
24.78
The result in Table 3.9 shows that patients with two types of
delusion accounted for the highest prevalence of 59.13%, while patients
with one type of delusion and no delusion just accounted for lowest
prevalence.
Table 3.10. Behavioral control of delusional types in patients with

schizophrenia
Behavioral Control
p
Numbe Percen
r (n)
t (%)
Yes
61
30.50
Persecutory delusion
0.000
No
139
69.50
Yes
42
27.27
Delusion of being followed
0.000
No
112
72.73
Yes
17
34.69
Contact delusion
0.032
No
32
65.31

Yes
10
38.46
Delusion of being controlled
0.239
No
16
61.54
Yes
7
24.14
Broadcasting thought
0.005
No
22
75.86
The result in Table 3.10 shows the prevalence of behavioral control
of each delusional type. Although this prevalence was not significantly
larger in three types of delusions, but it was also relativety high, from
24.14% to 38.46%.
3.3. Electroencephalogram in patients with schizophrenia
3.3.1. Energy property of electroencephalogram


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Figure 3.2. Alpha wave energy property in baseline EEG
The result in Figure 3.2 shows the alpha wave energy property in
the baseline EEG was significantly different between two groups
(p<0.001). In particular, the alpha wave energy property in the

schizophrenia group was statistically significantly lower than in the
control group in most areas of the cerebral cortex.

Figure 3.3. Delta wave energy property in baseline EEG
The result in figure 3.3 shows the difference of delta wave energy
property in the background EEG between two groups (p<0.001). In
which, the most difference was figured out at frontal area on both sides.


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Figure 3.4. Theta wave energy property in baseline EEG
The result in Figure 3.4 shows the diffenrence of theta wave energy
property in the background EEG between two groups (p<0.001). In
which, the most difference was figured out in the pre-frontal region on
both sides, the left frontal region, the central region on both sides and the
right occipital region.
3.3.2. Electroencephalogram amplitude

Figure 3.5. Alpha wave amplitude in baseline EEG
The result in Figure 3.5 shows alpha wave amplitude in the EEG
between two groups (p<0.001). In particular, alpha wave amplitude in the
schizophrenia group was significantly lower than in control group in
most regions of brain cortex.


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Figure 3.6. Delta wave amplitude in baseline EEG
The Table in Figure 3.6 shows the difference of delta wave

amplitude in the background EEG between two groups (p<0.001). The
most differences of delta wave amplitude were in prefrontal, frontal,
parietal, occipital, and temporal region.

Figure 3.7. Theta wave amplitude in baseline EEG
Figure 3.7 shows the difference of theta wave amplitude in the
EEG between two groups (p<0.001). The most differences of theta wave
amplitude were in frontal and occipital region on both sides.
3.3.3. Electroencephalogram frequency


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Figure 3.8. Alpha wave frequency in baseline EEG
The result in Figure 3.8 showed that there was no difference in the
alpha wave frequency between two groups.

Figure 3.9. Delta wave frequency in baseline EEG
The result in Figure 3.9 shows that there was no difference in delta
wave frequency in background EEG between two groups.


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Figure 3.10. Theta wave frequency in baseline EEG
The result in Figure 3.10 shows that there was no difference in
theta frequency in background EEG between two groups.
3.3.4. Relationship of energy property and hallucinations

Figure 3.11. Relationship between alpha wave energy property and

hallucinations in patients with schizophrenia
The result in Figure 3.11 shows that alpha wave energy property in
schizophrenic patients with hallucinations was higher than in
schizophrenic patients without hallucinations (p<0.001).

Figure 3.12. Relationship between delta wave energy property and
hallucinations in patients with schizophrenia
The result in Figure 3.12 shows that delta wave energy property in
schizophrenic patients with hallucinations was higher than in
schizophrenic patients without hallucinations (p<0.001).


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Figure 3.13. Relationship between theta wave energy property and
hallucinations in patients with schizophrenia
The result in Figure 3.13 shows that theta wave energy property in
schizophrenic patients with hallucinations was higher than in
schizophrenic patients without hallucinations (p<0.001).
3.3.5. The relationship between amplitude and hallucinations

Figure 3.14. Relationship between alpha wave amplitude and
hallucinations in patients with schizophrenia
The result in Figure 3.14 shows that alpha wave amplitude in
schizophrenic patients with hallucinations was higher than in
schizophrenic patients without hallucinations (p<0.001).


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Figure 3.15. Relationship between delta wave amplitude and
hallucinations in patients with schizophrenia
The result in Figure 3.15 shows that delta wave amplitude in
schizophrenic patients with hallucinations was higher than in
schizophrenic patients without hallucinations (p<0.05).

Figure 3.16. Relationship between theta wave amplitude and
hallucinations in patients with schizophrenia
The result in Figure 3.16 shows that theta wave amplitude in
schizophrenic patients with hallucinations was higher than in
schizophrenic patients without hallucinations (p<0.001).
3.4. Polymorphic features of COMT and ZNF804A genes of study
subjects
3.4.1. Polymorphic features of ZNF804A gene rs1344706
Result of Chi-square test of rs1344706 polymorphism in
schizophrenia and control groups were χ 2=0.02 and χ2=1.11, respectively,
showing that these values abided by the Hardy-Weinberg equilibrium
(p>0.05) and the distribution of polymorphism rs1344706 was random in


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study groups.
Table 3.11. The allele frequency of rs1344706 polymorphism in two
groups
Number of allele Allele frequency [n (%)]
Group (n)
[n (%)]
A
C

Schizophrenia
454
242
212
(n=227)
(100)
(53.30)
(46.70)
Control
184
95
89
(n=92)
(100)
(51.63)
(48.37)
Total (n)

638

337

301

χ2=0.88; p=0.767
The result in Table 3.11 shows that the frequency of allele A and C
in schizophrenia group was 53.30% and 46.70% respectively; In the
control group, it was 51.63% and 48.37%, respectively; There was no
difference between two groups (p=0.767). Thus, there was no difference
in the allele frequency of the rs1344706 polymorphism between two

groups.
Table 3.12. The allele frequency of rs1344706 polymorphism in males in
two groups
Allele frequency [n (%)]
Number of allele
Group (n)
[n (%)]
A
C
Schizophrenia
312
171
141
(n=227)
(100)
(54.81)
(45.19)
Control
102
49
53
(n=92)
(100)
(48.04)
(51.96)
Total (n)
414
220
194
χ2=1.156; p=0.282

The result in Table 3.12 shows that there was no difference in the
allele frequency of the rs1344706 polymorphism in males between two
groups (p=0.282).
Table 3.13. The allele frequency of rs1344706 polymorphism in females
of two groups
Allele frequency [n (%)]
Number of allele
Group (n)
[n (%)]
A
C
Schizophrenia
142
71
71


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(n=227)
Control
(n=92)

(100)
82
(100)

(50.00)
46
(56.10)

(50.00)
36
(43.90)

Total (n)

224

117

107

χ2=0.55; p=0.459
The result in Table 3.13 shows there was no difference in the allele
frequency of the rs1344706 polymorphism in females between two
groups (p=0.459).
Table 3.14. Genotypic distribution of rs1344706 polymorphysm in two
groups
Distribution of gene [n (%)]
Sample size
Group (n)
[n (%)]
AA
AC
CC
227
Schizophrenia
64
114

49
(n=227)
(28.19)
(50.22)
(21.59)
(100)
Control
92
22
51
19
(n=92)
(100)
(23.91)
(55.43)
(20.65)
319
86
165
68
Total (n)
χ2=0.816; p=0.665
The distribution of the three genotypes in the schizophrenia group
was 28.19%, 21.59%, and 50.22%, respectively; This prevalence in the
control group was 23.91%, 20.65%, and 55.43%, respectively; There was
no difference in the genotypic distribution of rs1344706 polymorphism
between two groups (p=0.665).
Table 3.15. Genotypic distribution of rs1344706 polymorpysm in males
in two groups
Distribution of gene [n (%)]

Sample size
Group (n)
[n (%)]
AA
AC
CC
156
Schizophrenia
44
83
29
(100)
(n=227)
(28.20)
(53.21)
(18.59)
51
Control
10
29
12
(100)
(n=92)
(19.61)
(56.86)
(23.53)
207
54
112
41

Total (n)


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χ2=1.658; p=0.437
The result in Table 3.15 shows that there was no difference in
genotypic distribution of rs1344706 polymorphism in males between two
groups (p=0.437).
Table 3.16. Genetic distribution of rs1344706 polymorphism in females
of two groups
Distribution of gene [n (%)]
Sample size
Group (n)
[n (%)]
AA
AC
CC
Schizophrenia
71
20
31
20
(n=227)
(100)
(28.17)
(43.66)
(28.17)
Control
41

12
22
7
(n=92)
(100)
(29.27)
(53.66)
(17.07)
112
32
53
27
Total (n)
χ2=1.89; p=0.389
The result in Table 3.16 shows that there was no difference in
genotypic distribution of rs1344706 polymorphism in females between
two groups (p=0.389).
3.4.2. Polymorphic features rs165599 COMT gene
The genotypic distribution of rs165599 polymorphism abided by
Hardy-Weinberg equilibrium in schizophrenia group (χ 2=0.73) and control
group (χ2=3.57).
Table 3.17. The allele frequency of rs165599 polymorphysm in two
groups
Allele frequency [n (%)]
Number of allele
Group (n)
[n (%)]
A
G
Schizophrenia

454
233
221
(n=227)
(100)
(51.32)
(48.68)
Control
184
89
95
(n=92)
(100)
(48.37)
(51.63)
Total (n)

638
χ2=0.456; p=0.499

322

316


22

The result in Table 3.17 shows that there was no difference in the
allele frequency of rs165599 polymorphism between schizophrenia and
control group with p=0.499.

Table 3.18. Allele frequency of rs165599 polymorphism in males of two
groups
Allele frequency [n (%)]
Number of allele
Group (n)
[n (%)]
A
G
Schizophrenia
312
165
147
(n=227)
(100)
(52.88)
(47.12)
Control
102
48
54
(n=92)
(100)
(47.06)
(52.94)
Total (n)

414

213

201

χ2=1.044; p=0.307
The result in Table 3.18 shows there was no difference in the allele
frequency of rs165599 polymorphism in males between two groups
(p=0.307).
Table 3.19. Allele frequency of rs165599 polymorphism in females of
two groups
Allele frequency [n (%)]
Number of allele
Group (n)
[n (%)]
A
G
Schizophrenia
142
68
74
(n=227)
(100)
(47.89)
(52.11)
Control
82
41
41
(n=92)
(100)
(50.00)
(50.00)

Total (n)

224

109

115

χ2=0.093; p=0.760
The result in Table 3.19 shows there was no difference in the allele
frequency of rs165599 polymorphism in females between two groups
(p=0.760).
Table 3.20. Genotypic distribution of rs165599 polymorphism in two
groups
Distribution of gene [n (%)]
Sample size
Group (n)
[n (%)]
AA
AG
GG
Schizophrenia
227
63
107
57


23

(n=227)
Control
(n=92)
Total (n)

(100)
92
(100)
319

(22.75)
17
(18.48)
80

(47.14)
55
(59.78)
162

(25.11)
20
(21.74)
77

χ2=5.355; p=0.069
The result in Table 3.20 shows that there was no difference in
genotypic distribution of rs165599 polymorphism between two groups
(p=0.069).
Table 3.21. Genotypic distribution of rs165599 polymorphism in males in

two groups
Distribution of gene [n (%)]
Sample size
Group (n)
[n (%)]
AA
AG
GG
Schizophrenia
156
46
73
37
(n=227)
(100)
(29.49)
(46.79)
(23.72)
Control
51
9
30
12
(n=92)
(100)
(17.65)
(58.82)
(23.53)
207
55

103
49
Total (n)
χ2=3.849; p=0.146
The result in Table 3.21 shows that there was no difference in
genotypic distribution of rs165599 polymorphism in males between two
groups (p=0.146).
Table 3.22. Genotypic distribution of rs165599 polymorphism in females
of two groups
Group (n)
Schizophrenia
(n=227)
Control
(n=92)
Total (n)

Sample size
[n (%)]
71
(100)
41
(100)
112

Distribution of gene [n (%)]
AA
AG
GG
17
34

20
(23.94)
(47.89)
(28.17)
8
25
8
(19.51)
(60.98)
(19.51)
25
59
28

χ2=1.910; p=0.385


24

The result in Table 3.22 shows that there was no difference in
genotypic distribution of rs165599 polymorphism in females between two
groups (p=0.385).

Chapter 4
DISCUSSION
4.1. General features of the study subjects
4.1.1. Age and gender of study subjects
In our study, age of patients were from 15 to 64 years old, in
which, the age group of 20-39 years old accounted for the 66.95%,
including the age group of 20-29 years old accounted for 40.43 %, and

the age group of 30-39 years old accounted for 26.52%. People over 50
years old and under 20 years old just accounted for 6.96% and 9.87%.
This result was consistent with the study of Pham Van Manh (2008). It
also shows that the age group of 20-39 years old accounted for the
highest prevalence of 69.45% [139].
Our research shows that 156 male patients accounted for 67.83%,
while female patients account for 32.17% with 74 people. The
male/female ratio was 2.1. This result was not unlikely to suggest that
schizophrenia usually affects males more than females. Thus, our results
were in line with the study of author Pham Van Manh (2008) in terms of
the of male/female ratio of 1.9 and consistent with Bui Quang Huy et. al.


25

(2016) in terms of percentage of male patients accounting for two-thirds
[1], [139].
4.1.2. Family and patient medical history
There were some major points in my study. Firstly, there was a
certain prevalence in schizophrenia group who had obstetric
abnormalities. This was a factor that affected the physical and intellectual
development of patients with schizophrenia, but there was not a major
relation to schizophrenia. Secondly, in schizophrenia group, patients who
have the family history of third degree relative having schizophrenia
accounted for 11.74%. Our result further contributed to confirming the
important role of genetic factors in the etiology of schizophrenia. Bui
Quang Huy et. al. (2016) showed that people who had history of first
degree relative having schizophrenia have risk of schizophrenia higher 20
times than the others.
4.2. Clinical features of the study subjects

4.2.1. Hallucination features of study subjects
There was 100% of patients with schizophrenia who experienced
hallucinations. This result was higher than Pham Van Manh’s (2008). He
figured out that patients with auditory hallucinations accounted for the
highest prevalence of 77.78%; patients with visual hallucinations
accounted for 11.11% and only one patient experienced tactile
hallucinations accounting for 0.92%. The difference was explained by the
influence of cultural factor and the fact that our study subjects onset later,
have longer disease duration, and were older. [139], [148], [149].
Among hallucinations, comment auditory hallucination accounted
for the highest prevalence (79.13%), followed by inducement auditory
hallucinations accounting for 33.04%, and conversation auditory
hallucinations accounting for 25.22%. The following auditory
hallucinations accounted for low prevalence, such as: command auditory
hallucinations (6.09%) and echoing thought (4.35%). Our research result
was also in accordance with Pham Van Manh’s (2008) [139]. The result of
this study showed that the majority of patients experienced one type of
hallucination, accounting for 47.83%, and two types of hallucinations,
accounting for 47.39%. There were few patients with schizophrenia did
not experience hallucinations (3.04%) and three types of hallucinations
(1.74%).
The result of this study shows that the prevalence of auditory
hallucinations which control behaviors was quite high, being from 20%
(for echoing thought) to 43.42% (command auditory hallucinations). This