Nghiên cứu đặc điểm hình thái một số cấu trúc não và nồng độ serotonin huyết tương, dịch não tủy ở bệnh nhân trầm cảm mức độ nặng tt tiếng anh

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF NATIONAL DEFENSE VIETNAM MILITARY MEDICAL UNIVERSITY DO XUAN TINH STUDY ON MORPHOLOGICAL CHARACTERISTICS OF SOME BRAIN STRUCTURES AND SEROTONIN CONCENTRATION IN PLASMA AND CEREBROSPINAL FLUID IN SEVERE DEPRESSION PATIENTS Major: Neuroscience Code: 9720159 MEDICAL DOCTORAL THESIS SUMMARY HANOI - 2020 THE WORK IS COMPLETED AT VIETNAM MILITARY MEDICAL UNIVERSITY Supervisors: Prof Dr CAO TIEN DUC Prof Dr NGUYEN LINH TOAN Opponent 1: Dr Nguyen Doan Phuong Opponent 2: Prof Dr Do Duc Cuong Opponent 3: Prof Dr Pham Van Manh The thesis will be defended in front of the school-level thesis council at: h, date month year 2020 The thesis can be found at: National Library Vietnam Military Medical Academy library QUESTION The urgency of the topic Depression disorder is a common endogenous psychiatric state, diverse and abundant clinical symptoms that adversely affect the health and working capacity of patients Every year in the world hundreds of millions of people are found to be depressed According to the World Health Organization, depression disorder will be the second leading cause of working capacity loss in 2020 and first in 2030 Currently, there are many assumptions about the pathogenesis of depression, but the most important hypothesis is the morphological changes in some cerebral structures and the deficiency of the neurotransmitter serotonin in the brain’s sinap gap, which is thought to be the cause of depression In Vietnam, there are no studies on morphology of some brain structures and changes in serotonin concentration in cerebrospinal fluid of patients From the above issues, we conduct research on the subject “Study on morphological characteristics of some cerebral structures and serotonin concentration in plasma, cerebrospinal fluid in severe depression patients” Objectives of the topic - To describe clinical features in severe depression patient - To analyze morphological characteristics of some cerebral structures and serotonin concentration in plasma and cerebrospinal fluid concentration in severe depression patients - To investigate the relationship between serotonin concentration in plasma, cerebrospinal fluid and morphology of some cerebral structures and clinical severe depression patients New contributions of the thesis - Identify changes in the volume of some brain structures in severe depression patients such as: the intracranial volume, The volume of the lateral ventricles and rd-ventricles, frontal lobe volume, hippocampal volume and The volume of caudal nucleus Find a link between brain structure and some clinical symptoms such as psychotic symptoms, suicidal intent and behavior, and duration of illness - Serotonin concebtration in serebrospinal fluid in severe depression patients decreased significantly compared to normal people Serotonin concebtration are associated with a number of factors such as age, gender, duration of illness, number of hospital admissions, and are related to some clinical symptoms such as; emotional, psychotic and suicidal behavior The layout of the thesis - The thesis consists of 136 pages: + Question: pages + Chapter 1: Overview of document: 36 pages + Chapter 2: Subjects and research methods: 20 pages + Chapter 3: Research results: 36 pages + Chapter 4: Discussion: 38 pages + Conclusion: pages + Recommendation: page + List of works: page + 44 tables; charts; pictures - References: The thesis consists of 141 documents, including 20 Vietnamese documents, 121 foreign languages documents, 45 documents in the last years CHAPTER OVERVIEW OF DOCUMENTS 1.1 GENERAL RESEACH ON CLINICAL DEPRESSION 1.1.1 Concept of depressive disorder and severe depression Concept of depressive disorder and severe depression according to ICD 10 - 1992 1.1.2 Epidemiology of depressive disorder Depression is a common condition in the world and its prevalence is increasing Studies on depression disorders have shown that the lifetime risk of this disease is 10% -25% for women and 5% -12% for men According to DSM-5 (2013), the prevalence of depression for 12 months in the US is 7% of the population and 1.5% of the US population has a diagnostic criteria for chronic depression The prevalence of mood disorder in the US is 0.5% of the population 1.1.3 Research on clinical characteristics of depression disorder The clinical manifestations of depression in general and severe depressive disorder in particular are diverse and abundant, presenting the disorder in most high-level human neurological functions such as emotions, perception, thinking, memory, attention, behavior Both of the most popular mental illness classification systems today, ICD10 and DSM-5, have relatively uniform symptoms of clinical depression disorder 1.2 RESEARCH ON BRAIN IMAGING DEPRESSION DISORDER Today, more and more studies in the world use brain imaging to learn about the structure and function of the brain in depression disorder Studies have shown that depression has a lot of differences in the structure and function of the nervous system related to the emotional processing and mood of patients Moreover, several studies have shown that the structure and function of these systems change when treated with medication and psychotherapy Recent studies have shown that some areas of the brain undergo structural changes, especially changes in volume of depression disorder On the computerized tomography (CT) imaging of the brain, some depressed patients have enlarged ventricles, especially in depressed patients with psychosis, the more clearly the images of ventricular dilatation are clearer Research using magnetic resonance imaging (MRI) showed that there was an image of nuclei atrophy and frontal lobe and had anomalies in the oysters compared to the symptom group Brain imaging studies using MRI showed that depressed patients with ventricular psychosis have a wider dilatation than the symptom group and a larger size of white matter than nonpsychotic depression patients In depressed patients with psychosis, there is the appearance of cerebral atrophy, ventricular dilatation, atrial temporal atrophy Especially the recent studies have shown that the hippocampus volume is reduced, accompanied by a decrease in new nerve cell regeneration in the teeth It is also found that the atrophy of the frontal cortex and the almonds are areas of emotional control, mood, which leads to reduced nerve cell flexibility and this may play a major role in etiology of depression CT imaging and MRI of the cranial brain showed the ventricle and the widening gaps in depression, especially in the elderly These changes are milder in Alzheimer’s patients but more clear in normal people Deep alba lesions and severe injuries are associated with severe prognosis 1.3 RESEARCH ON SEROTONIN 1.3.1 Research on the function of serotonin Serotonin (5- Hydroxytryptamin -5-HT) is a neurotransmitter, they are abundant in plants (such as bananas), but are difficult to absorb through the intestine and are quickly metabolized, so there is no poisoning when eating food with much serotonin In mammals, about 90% of serotonin is in the chromophilic cells of the intestine, 8% in platelets, 2% in the central nervous system (especially in the pineal gland and the hypothalamus) Normally, serotonin in the blood is about 0.06 - 0.22 µg/ml, mainly located in platelets and in mastocyte cells Serotonin is an intermediate neurotransmitter, involved in regulating many functions of the body: central nervous system, platelets, organs, sleep cycle 1.3.2 Research on serotonin concentration in plasma and relationship with clinical characteristics in depression patients Many of these studies demonstrate the important role of serotonin in the pathogenesis of depression A deficiency of serotonin in the sinap cleft is considered a major cause of depression Sadock B.J (2007) suggested that the lower the serotonin concentration in the sinap cleft, the worse the depression was This hypothesis is supported by the fact that depressed patients treated with serotonin selective reuptake inhibitor antidepressants such as fluoxetin cause serotonin concentration in the sinap cleft to return to normal, the depression state will decrease Many studies showed that depressed patients have an imbalance of neurotransmitters, natural substances that allow brain cells to communicate with each other and to other cells, the type of transmitters associated with depression are serotonin and norepinephrine Serotonin deficiency causes sleep disorders, irritability and anxiety disorders along with depression Reducing the amount of norepinephrine (the substance that regulates agility and agitation) can cause fatigue and emotional distress Quantitative serotonin studies in acute depression patients have found that 50% of cases have halved and 30% of cases have serotonin blood reduced by 2/3 compared to normal people Studies confirm that in severely depressed patients there is a drop in serotonin levels and serotonin levels that affect the clinical characteristics of depressed patients However, we have not been able to confirm whether changes in serotonin concentration are more or less and directly affect a symptom or group of symptoms in severe depression patients, or severe depression Because, the clinical characteristics of severe depression are many other factors involved But the results confirm that there is a strong correlation between changes in serotonin concentration in remission of clinical symptoms in severe depression patients CHAPTER SUBJECT AND METHOD OF THE STUDY 2.1 RESEARCH SUBJECT 2.1.1 Number of research subjects - Group of patients: 72 patients (35 male, 37 female) aged from 20 to 61, diagnosed with severe depression according to ICD-10F diagnostic criteria (1992) Inpatient treatment at Psychiatry Department – 103 Military Medical Hospital 103 from May 2015 to June 2018 + 72 patients were clinically examined and blood tested to quantify serotonin concentration in plasma (PL); Randomly selected: 32 patients with MRI at brain and 36 patients with lumbar puncture to take cerebrospinal fluid (CSF) - Symptom group: 68 cases (41 men, 27 women) aged 19 to 61, without depression and serotonin related body disease: All 68 cases were tested for blood amount of serotonin concentration in plasma; 32 cases of lumbar puncture are taken for CSF; 41 cases of normal Vietnamese adults were measured volume of some brain structures 2.1.2 Research patient selection criteria Patients diagnosed with severe depression according to the criteria of the 10th International Classification of Diseases (ICD-10) 2.1.3 Exclusion criteria Patients with general physical conditions are at risk of altering serotonin concentration in plasma, such as gastrointestinal, peripheral neuropathy, and endocrine system diseases The patients with brain damage or sequelae of meningococcal disease, the patients with drug addicts, or psychotropic substances appearing after severe depression disorder 2.2 RESEARCH METHOD 2.2.1 Research design We use cross-sectional and analytical methods 2.2.2 Morphological tool for several brain structures Research on brain morphology uses images taken from 1.5 Tesla magnetic resonance imaging system (Philips, Netherlands, manufactured in 2010) at the Department of Imaging Diagnosis, 103 Military Hospital Video-filed data is backed up on DVDs for later analysis Analysis of magnetic resonance image data is performed on a system, including computers with powerful processors, large storage hard drives and graphics cards (GeForce 2Gb, Gigabyte), installed FreeSurfer specialized software (version 6.0; http://surfer.nmr.mgh.harvard.edu) and Mango (version 4.0.1; http://www.uthscsa.edu/) 2.2 Tool to assess serotonin concentration test results Equipment and means of quantifying serotonin concentration in plasma by ELISA method (Enzym - Linked Immuno Sorbent Assay) This is a Sandwich-type enzyme immunoassay based on the specific reaction between antibodies bound at the bottom of the well and the serotonin antigen present in plasma of patients 2.3 Data processing Data processing using SPSS 20.0 statistical software CHAPTER RESEARCH RESULT 3.1 General characteristics of patients Average age 39.89 ± 11.81; men 48.61%, women 51.39% Symptom group and disease group not differ in age and gender 3.2 Morphological characteristics of some brain structures in severe depression patients Table 3.16 Intracranial volume and frontal lobe volume in the two study groups Disease group Symptom group Brain structure (n = 32) (n = 41) p volume (cm3) (cm X ± SD X ± SD Intracranial volume 1422,09 ± 128,60 1520,36 ± 131,14 < 0,05 Full frontal lobe 158,93 ± 21,98 168,80 ± 20,73 < 0,05 Right frontal lobe 79,21 ± 11,34 83,75 ± 10,00 > 0,05 Left frontal lobe 79,27 ± 10,73 85,04 ± 10,81 < 0,05 Intracranial volume and frontal lobe volume in the group of severe depression patients were lower than in the symptom group, p 0,05 The results showed that the volume of lateral ventricular and third ventricular in the depressive patient group, is statistically significant p 80 ng/ml 25 44,6 22,7 (d) : Chi-square test (χ ); : Fisher exact test The results showed that the rate of decreased serotonin concentration in plasma in the unstable emotion group (77.3%) was higher than the stable emotion group (50.0%), with OR = 0.29 ( 0.080.92); p 0,05 ≤ 80 ng/ml 24 57,1 18 60 > 80 ng/ml 18 42,9 12 40 Self-charged paranoia Decreased serotonin in PL Yes No 0,29 (0,09 - 0,90); n % n % p(c) < 0,05 ≤ 80 ng/ml 35,3 36 65,5 > 80 ng/ml 11 64,7 19 34,5 The rate of decreased serotonin concentration in plasma in the non-paranoid self- charged group (65.5%) was higher than the paranoid self- charged group (35.3%), with OR = 0.29 (0.09 - 0.90); p 80 ng/ml 50,0 22 39, p(c) > 0,05 Decreased ≤ 1,6 ng/ml 15,75 85,7 27,6 serotonin (1,63-152,18); > 1,6 ng/ml 14,3 21 72,4 in CSF p(d < 0,01 The results showed that the rate of the group with reduced serotonin concentration in cerebrospinal fluid ≤ 1.6 ng/ml with suicidal behavior (85.7%) was much higher than the group without suicidal behavior (27.6%), with OR = 15.8 (1,63-152,18); p