AND TRAINING DEFENSEVIETNAM MILITARY MEDICAL UNIVERSITY DO XUAN TINH STUDY ON MORPHOLOGICAL CHARACTERISTICS OF SOME BRAIN STRUCTURES AND SEROTONINCONCENTRATION IN PLASMA AND CEREBROSPINA
Trang 1AND TRAINING DEFENSE
VIETNAM MILITARY MEDICAL UNIVERSITY
DO XUAN TINH
STUDY ON MORPHOLOGICAL CHARACTERISTICS
OF SOME BRAIN STRUCTURES AND SEROTONINCONCENTRATION IN PLASMA AND CEREBROSPINALFLUID IN SEVERE DEPRESSION PATIENTS
Major: NeuroscienceCode: 9720159
MEDICAL DOCTORAL THESIS SUMMARY
HANOI - 2020
Trang 2AT VIETNAM MILITARY MEDICAL UNIVERSITY
at: h, date month year 2020
The thesis can be found at:
1 National Library
2 Vietnam Military Medical Academy library
Trang 31 The urgency of the topic
Depression disorder is a common endogenous psychiatricstate, diverse and abundant clinical symptoms that adversely affectthe health and working capacity of patients Every year in the worldhundreds of millions of people are found to be depressed According
to the World Health Organization, depression disorder will be thesecond 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 morphologicalchanges in some cerebral structures and the deficiency of theneurotransmitter 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 brainstructures and changes in serotonin concentration in cerebrospinalfluid 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”
2 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.
Trang 43 New contributions of the thesis
- Identify changes in the volume of some brain structures insevere depression patients such as: the intracranial volume, Thevolume of the lateral ventricles and rd-ventricles, frontal lobevolume, 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 ofillness
- Serotonin concebtration in serebrospinal fluid in severe
depression patients decreased significantly compared to normalpeople Serotonin concebtration are associated with a number offactors such as age, gender, duration of illness, number of hospitaladmissions, and are related to some clinical symptoms such as;emotional, psychotic and suicidal behavior
4 The layout of the thesis
- The thesis consists of 136 pages:
+ Question: 2 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: 2 pages
+ Recommendation: 1 page
+ List of works: 1 page
+ 44 tables; 8 charts; 5 pictures
- References: The thesis consists of 141 documents, including 20 Vietnamese documents, 121 foreign languages documents, 45 documents in the last 5 years
Trang 5CHAPTER 1
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 depressionaccording to ICD 10 - 1992
1.1.2 Epidemiology of depressive disorder
Depression is a common condition in the world and itsprevalence is increasing Studies on depression disorders have shownthat the lifetime risk of this disease is 10% -25% for women and 5% -12% for men According to DSM-5 (2013), the prevalence ofdepression 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 severedepressive disorder in particular are diverse and abundant, presentingthe disorder in most high-level human neurological functions such asemotions, perception, thinking, memory, attention, behavior Both
of the most popular mental illness classification systems today,
ICD-10 and DSM-5, have relatively uniform symptoms of clinicaldepression 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 depressiondisorder Studies have shown that depression has a lot of differences
in the structure and function of the nervous system related to theemotional processing and mood of patients Moreover, severalstudies have shown that the structure and function of these systemschange when treated with medication and psychotherapy
Trang 6Recent studies have shown that some areas of the brainundergo structural changes, especially changes in volume ofdepression 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 theimages of ventricular dilatation are clearer Research using magneticresonance imaging (MRI) showed that there was an image of nucleiatrophy and frontal lobe and had anomalies in the oysters compared
to the symptom group Brain imaging studies using MRI showed thatdepressed patients with ventricular psychosis have a wider dilatationthan the symptom group and a larger size of white matter than non-psychotic depression patients
In depressed patients with psychosis, there is the appearance ofcerebral atrophy, ventricular dilatation, atrial temporal atrophy.Especially the recent studies have shown that the hippocampusvolume is reduced, accompanied by a decrease in new nerve cellregeneration in the teeth It is also found that the atrophy of thefrontal cortex and the almonds are areas of emotional control, mood,which leads to reduced nerve cell flexibility and this may play amajor role in etiology of depression
CT imaging and MRI of the cranial brain showed the ventricleand the widening gaps in depression, especially in the elderly Thesechanges are milder in Alzheimer’s patients but more clear in normalpeople Deep alba lesions and severe injuries are associated withsevere 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 toabsorb 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,
Trang 78% in platelets, 2% in the central nervous system (especially in thepineal gland and the hypothalamus) Normally, serotonin in the blood
is about 0.06 - 0.22 µg/ml, mainly located in platelets and inmastocyte cells Serotonin is an intermediate neurotransmitter,involved in regulating many functions of the body: central nervoussystem, 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 ofserotonin in the pathogenesis of depression A deficiency of serotonin
in the sinap cleft is considered a major cause of depression SadockB.J (2007) suggested that the lower the serotonin concentration inthe sinap cleft, the worse the depression was This hypothesis issupported by the fact that depressed patients treated with serotoninselective reuptake inhibitor antidepressants such as fluoxetin causeserotonin concentration in the sinap cleft to return to normal, thedepression state will decrease
Many studies showed that depressed patients have animbalance of neurotransmitters, natural substances that allow braincells to communicate with each other and to other cells, the type oftransmitters associated with depression are serotonin andnorepinephrine Serotonin deficiency causes sleep disorders,irritability and anxiety disorders along with depression Reducing theamount of norepinephrine (the substance that regulates agility andagitation) can cause fatigue and emotional distress Quantitativeserotonin studies in acute depression patients have found that 50% ofcases have halved and 30% of cases have serotonin blood reduced by2/3 compared to normal people
Studies confirm that in severely depressed patients there is adrop in serotonin levels and serotonin levels that affect the clinicalcharacteristics of depressed patients However, we have not been able
to confirm whether changes in serotonin concentration are more or
Trang 8less and directly affect a symptom or group of symptoms in severedepression patients, or severe depression Because, the clinicalcharacteristics of severe depression are many other factors involved.But the results confirm that there is a strong correlation betweenchanges in serotonin concentration in remission of clinical symptoms
in severe depression patients
CHAPTER 2 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) agedfrom 20 to 61, diagnosed with severe depression according to ICD-10F diagnostic criteria (1992) Inpatient treatment at PsychiatryDepartment – 103 Military Medical Hospital 103 from May 2015 toJune 2018
+ 72 patients were clinically examined and blood tested toquantify 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 68cases were tested for blood amount of serotonin concentration inplasma; 32 cases of lumbar puncture are taken for CSF; 41 cases ofnormal Vietnamese adults were measured volume of some brainstructures
2.1.2 Research patient selection criteria
Patients diagnosed with severe depression according to thecriteria of the 10th International Classification of Diseases (ICD-10)
2.1.3 Exclusion criteria
Patients with general physical conditions are at risk ofaltering serotonin concentration in plasma, such as gastrointestinal,
Trang 9peripheral neuropathy, and endocrine system diseases The patientswith brain damage or sequelae of meningococcal disease, the patientswith drug addicts, or psychotropic substances appearing after severedepression 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 1.5Tesla magnetic resonance imaging system (Philips, Netherlands,manufactured in 2010) at the Department of Imaging Diagnosis, 103Military Hospital Video-filed data is backed up on DVDs for lateranalysis Analysis of magnetic resonance image data is performed on
a system, including computers with powerful processors, largestorage 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 3 Tool to assess serotonin concentration test results
Equipment and means of quantifying serotonin concentration
in plasma by ELISA method (Enzym - Linked Immuno SorbentAssay) This is a Sandwich-type enzyme immunoassay based on thespecific reaction between antibodies bound at the bottom of the welland the serotonin antigen present in plasma of patients
2.3 Data processing
Data processing using SPSS 20.0 statistical software
Trang 10CHAPTER 3 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 do 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
Brain structure
volume (cm3) (cm
Disease group (n = 32)
X ± SD
Symptom group (n = 41)
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 > 0,05Left frontal lobe 79,27 ± 10,73 85,04 ± 10,81 < 0,05Intracranial volume and frontal lobe volume in the group of severedepression patients were lower than in the symptom group, p <0.05
Table 3.17 Ventricular volume in 2 study groups
Brain structure
volume (cm3)
Disease group (n = 32)
X ± SD
Symptom group (n = 41)
Right ventricle 6,47 ± 2,57 5,19 ± 3,26 < 0,05Right ventricle 7,49 ± 3,12 5,88 ± 3,46 < 0,05
Trang 11Table 3.18 Hippocampus volume in the studied patient group Brain structure
volume (cm3)
Disease group (n = 32)
X ± SD
Symptom group (n = 41)
X ± SD
p
Right hippocampus 3,99 ± 0,77 4,41 ± 0,40 < 0,01Left hippocampus 3,92 ± 0,41 4,47 ± 0,48 < 0,001
Whole ippocampus 7,99 ± 0,77 8,88 ± 0,85 < 0,001 The results showed that the whole hippocampus volume in the
depressive patient group (7.99 ± 0.77 cm3) was smaller than thewhole hippocampus volume in the symptom group (8.88 ± 0.85 cm3)
X ± SD
Symptom group (n = 41)
X ± SD
p
Right caudatennucleus 3,31 ± 0,44 3,45 ± 0,51 > 0,05Left caudatennucleus 3,16 ± 0,42 3,55 ± 0,48 < 0,01Bilateral audatennucleus 6,47 ± 0,86 7,00 ± 0,96 < 0,05
The results showed that the volume of caudatennucleus in thedepression group (6.47 ± 0.86 cm3) was smaller than one in thesymptom group (7.00 ± 0.96 cm3) is statistically significant p <0.05
3.3 Serotonin concentration in plasma and in cerebrospinal fluid
in severe depression patients.
Table 3.21 Serotonin concentration in plasma and in
cerebrospinal fluid in study groups
Trang 12125,24 ± 118,51
85,58 (31,05; 189,29)(n = 68)
< 0,05
CSF
2,11 ± 1,13
2,02(1,37; 2,86)(n = 36)
6,34 ± 2,86
6,09(4,27; 7,81)(n = 32)
< 0,001
(b) : Mann-Withney U Test The results showed that Serotonin
concentration in PL and in CSF in severe depression disorder patientswere much lower than the symptom group, with p <0.05 and p
<0.001
Chart 3.8 showed that the rate of cerebrospinal fluid
serotonin reduction ≤ 1.6 ng/ml in the depression disorder group(38.9%) was much higher than the symptom group (3.1%),statistically significant with OR = 19.73 (2.41-161.26), p <0.001
Table 3.22 Serotonin concentration in plasma and in cerebrospinal
fluid in both genders
92,21 ± 96,32 44,61(21,53; 157,79)(n = 41)
> 0,05
Female
75,74 ± 91,91
83,30(17,16; 148,99)(n = 37)
175,39 ± 132,60
159,09(64,26; 234,07)(n = 27)
5,99 ± 2,67
5,80(4,02; 7,09)(n = 24)
< 0,001
Female
1,98 ± 1,27
1,60(1,22; 2,71)(n = 13)
7,37 ± 3,16
7,92(5,160; 9,50)(n = 8)
< 0,01
The results showed that serotonin concentration incerebrospinal fluid in male patients with severe depression disorderwas much lower than the symptom group, with p <0.001 serotonin
Trang 13concentration in cerebrospinal fluid in female patients with severedepression was much lower than those in the symptom group, with p
<0.01
3.4 Relationship between serotonin concentration in cerebrospinal fluid with clinical symptoms in severe depression patients
Table 3.26 The rate of change in the serotonin concentration in
plasma with emotional disorder
Group
OR (95%,CI); p
Decreased
serotonin in PL
Nervous, scared
0,5 (0,20 –1,24);
(c) : Chi-square test (χ 2 ); (d) : Fisher exact test
The results showed that the rate of decreased serotoninconcentration in plasma in the unstable emotion group (77.3%) washigher than the stable emotion group (50.0%), with OR = 0.29 ( 0.08-0.92); p <0.05