Research on features of electroencephalogram and some polymorphisms of comt, znf804a gene in patients with 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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ents 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 hallucinations Number (n) Percent (%) p Comment 182 79.13 0.000 Inducement 76 33.04 Conversation 58 25.22 Command 14 6.09 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 Content of hallucinations Number (n) Percent (%) p None of hallucination 7 3.04 0.000 One type of hallucination 110 47.83 Two types of hallucination 109 47.39 Three types of hallucination 4 1.74 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 Number (n) Percent (%) p Comment Pseudo 135 74.18 0.000 True 47 25.82 Inducement Pseudo 59 77.63 0.000 True 17 22.37 Conversation Pseudo 49 84.48 0.000 True 9 15.52 Command Pseudo 9 64.29 0.285 True 5 35.71 Echoing thought Pseudo 6 60 0.754 True 4 40 The results in Table 3.6 shows that the prevalence of pseudo-hallucinations 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 hallucinations Behavioral control Number (n) Percent (%) p Comment auditory hallucination Yes 49 26.92 0.000 No 133 73.08 Inducement auditory hallucination Yes 33 43.42 0.251 No 43 56.58 Conversation auditory hallucination Yes 15 25.86 0.000 No 43 74.14 Command auditory hallucination Yes 10 71.43 0.180 No 4 28.57 Echoing thought 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 Type of delusions Number (n) Percent (%) p Contact delusion 49 21.30 < 0.000 Persecutory delusion 200 86.96 Delusion of being followed 154 66.96 Broad casting thought 29 12.61 Controled delusion 26 11.30 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 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 (n) Percent (%) p None of delusion 4 1.74 0.000 One type 33 14.35 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 Number (n) Percent (%) p Persecutory delusion Yes 61 30.50 0.000 No 139 69.50 Delusion of being followed Yes 42 27.27 0.000 No 112 72.73 Contact delusion Yes 17 34.69 0.032 No 32 65.31 Delusion of being controlled Yes 10 38.46 0.239 No 16 61.54 Broadcasting thought Yes 7 24.14 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 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. 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. 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 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. 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). 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). 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 χ2=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 study groups. Table 3.11. The allele frequency of rs1344706 polymorphism in two groups Group (n) Number of allele [n (%)] Allele frequency [n (%)] A C Schizophrenia (n=227) 454 (100) 242 (53.30) 212 (46.70) Control (n=92) 184 (100) 95 (51.63) 89 (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 Group (n) Number of allele [n (%)] Allele frequency [n (%)] A C Schizophrenia (n=227) 312 (100) 171 (54.81) 141 (45.19) Control (n=92) 102 (100) 49 (48.04) 53 (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 Group (n) Number of allele [n (%)] Allele frequency [n (%)] A C Schizophrenia (n=227) 142 (100) 71 (50.00) 71 (50.00) Control (n=92) 82 (100) 46 (56.10) 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 Group (n) Sample size [n (%)] Distribution of gene [n (%)] AA AC CC Schizophrenia (n=227) 227 (100) 64 (28.19) 114 (50.22) 49 (21.59) Control (n=92) 92 (100) 22 (23.91) 51 (55.43) 19 (20.65) Total (n) 319 86 165 68 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 Group (n) Sample size [n (%)] Distribution of gene [n (%)] AA AC CC Schizophrenia (n=227) 156 (100) 44 (28.20) 83 (53.21) 29 (18.59) Control (n=92) 51 (100) 10 (19.61) 29 (56.86) 12 (23.53) Total (n) 207 54 112 41 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 Group (n) Sample size [n (%)] Distribution of gene [n (%)] AA AC CC Schizophrenia (n=227) 71 (100) 20 (28.17) 31 (43.66) 20 (28.17) Control (n=92) 41 (100) 12 (29.27) 22 (53.66) 7 (17.07) Total (n) 112 32 53 27 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 (χ2=0.73) and control group (χ2=3.57). Table 3.17. The allele frequency of rs165599 polymorphysm in two groups Group (n) Number of allele [n (%)] Allele frequency [n (%)] A G Schizophrenia (n=227) 454 (100) 233 (51.32) 221 (48.68) Control (n=92) 184 (100) 89 (48.37) 95 (51.63) Total (n) 638 322 316 χ2=0.456; p=0.499 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 Group (n) Number of allele [n (%)] Allele frequency [n (%)] A G Schizophrenia (n=227) 312 (100) 165 (52.88) 147 (47.12) Control (n=92) 102 (100) 48 (47.06) 54 (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 Group (n) Number of allele [n (%)] Allele frequency [n (%)] A G Schizophrenia (n=227) 142 (100) 68 (47.89) 74 (52.11) Control (n=92) 82 (100) 41 (50.00) 41 (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 Group (n) Sample size [n (%)] Distribution of gene [n (%)] AA AG GG Schizophrenia (n=227) 227 (100) 63 (22.75) 107 (47.14) 57 (25.11) Control (n=92) 92 (100) 17 (18.48) 55 (59.78) 20 (21.74) Total (n) 319 80 162 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 Group (n) Sample size [n (%)] Distribution of gene [n (%)] AA AG GG Schizophrenia (n=227) 156 (100) 46 (29.49) 73 (46.79) 37 (23.72) Control (n=92) 51 (100) 9 (17.65) 30 (58.82) 12 (23.53) Total (n) 207 55 103 49 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) Sample size [n (%)] Distribution of gene [n (%)] AA AG GG Schizophrenia (n=227) 71 (100) 17 (23.94) 34 (47.89) 20 (28.17) Control (n=92) 41 (100) 8 (19.51) 25 (60.98) 8 (19.51) Total (n) 112 25 59 28 χ2=1.910; p=0.385 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. (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 was clearly shown in the analysis of the influence of auditory hallucinations on behavior in schizophrenia group. The effect of auditory hallucinations on patient behaviors in this study was consistent with reports of many studies on the role of hallucinations in violent behavior in schizophrenia patients [6]. 4.2.2. Delusional features of study subjects Delusions are the most obvious symptoms of thinking content disorder. The content of these delusions can be varied, including: persecution, contacting, grandiosity, etc. The most common delusion was persecutory delusion (89.96%). Delusion of being followed accounted for 66.96%; prevalence of contact delusion was 21.30%. Delusion of being followed was the chateristic symptom of schizophrenia. This result was not in line with Pham Van Manh’s (2008) and Nguyen Thanh Binh’s (2010) [139], [148]. Although, most behaviors was not controlled by delusions, but in this study the prevalence of delusions which controlling behaviors from 24.14% to 38.46%. It should be noted that the majority of patients with schizophrenia experienced two different types of delusions (accounting for 59.13%) or three different types of delusions (accounting for 24.78%). This result was consistent with previous study in the fact that delusions play a certain role in violent behavior in schizophreni a[8]. 4.3. Electroencephalogram on schizophrenia patients 4.3.1. Changes the energy property on the electroencephalogram In this study, we found that the delta and theta wave energy property in the schizophrenia group was higher than in the control group in most of cortical areas. In particular, the energy property of delta waves and theta waves was highgest at the pre-frontal in both sides and the left frontal region. In contrast, the alpha wave energy property was lower in the schizophrenia group. These results were massively concerned when we want to determine the value of wave energy property on EEG analysis. Thus, we suggest that there were increases of activity of delta waves, theta waves and decreases of activity of alpha waves in patients with schizophrenia compared to the control group. The changes of activity of EEG waves evaluated the imbalance between inhibitory and excitatory activities in the cerebral cortex in patients with schizophrenia. This result was consistent with the study of Moeini M. et. al. (2014). He analyzed EEG in 40 patients with schizophrenia and 40 controls with 23 electrodes amd found that the alpha wave energy property decreased in schizophrenia in all areas, except frontal and temporal region (p<0.05); At the same time, alpha wave energy property had a difference in the front and middle of the right hemisphere [54]. In our study, we found that theta wave energy property increased in patients compared to healthy people, and this result was similar to Kim J.W. et. al. (2015). He also found that theta wave activity was significantly different among regions: highest in the occipital region and lowest in the central region (F=3.510; p=0.034; df=1.881). It should be noted that delta waves and theta waves exhibit inhibitiory activity of the cerebral cortex, while alpha waves exhibit excitatory activity in the cerebral cortex. Increases of delta and theta wave activity and decrease of alpha wave activity indicate a state of inhibitory activity in the cerebral cortex in patients with schizophrenia. Our study of delta wave energy property was also consistent with the results of Begić D. et. al. (2011) in the fact that delta wave activity in schizophrenia patients was higher than in healthy people, in which, the highest energy property was at the right pre-frontal region and the lowest was at the left temporal region. Moreover, our results also show that there were differences in wave energy property in distinctive regions of the cerebral cortex as well as in the intermittent photic stimulation in the EEG such as light stimulation test. However, this change was also seen in the control group. Therefore, we believe that the changes in wave energy property by region of recording and intermittent are just the normal change of EEG wave. 4.3.2. Changes the amplitude of the waves on the electroencephalogram From the fact of results of the wave amplitude on the EEG, we suggest that the amplitude of delta waves and theta waves in the schizophrenia were higher in pre-frontal, frontal, and cetral regions on both sides. The difference was more clearly figured out when we conducted light stimulation test. This result was consistent with previous studies. This difference was mainly seen in the occipital region on both sides. Our results were similar to study of Itoh T. et. al. (2011) in the fact that the delta wave amplitude in schizophrenia increased significantly, especially at the left temporal region (t=4.27). Ranlund S. et. al. (2014) found that the highest delta wave amplitude in chronic schizophrenia compared with acute schizophrenia and healthy people (p<0.001). In the study of Ngo Ngoc Tan in 116 patients and 118 healthy Vietnamese people, the delta wave amplitude increased significantly, compared to the controls (52.95±16.24μV vs 32.85±13.18μV) [48], [63], [64]. There have been also many studies showing that there is no change in alpha wave in schizophrenia patients. Itoh T. et. al. (2011) analysed EEG data from 17 patients with schizophrenia and 17 healthy people and found that there was no difference in alpha wave amplitude in schizophrenia [64]. Similarly, the differences of the EEG wave amplitude before and after inmittent photic stimulation were figured out in both of schizophrenia and healthy people. Therefore, this differenc

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