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:
1. National Library
2. Vietnam Military Medical Academy library


1
QUESTION
1. 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”
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.


2
3. 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.
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.


3
CHAPTER 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 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.


4

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,


5
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


6
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 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) 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,


7
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;
) and Mango (version 4.0.1;
/>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 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


8
CHAPTER 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
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.
Table 3.17. Ventricular volume in 2 study groups
Disease group
Symptom group
Brain structure
(n = 32)
(n = 41)
p
volume (cm3)
X ± SD
X ± SD
Right ventricle

6,47 ± 2,57
5,19 ± 3,26
< 0,05
Right ventricle
7,49 ± 3,12
5,88 ± 3,46
< 0,05
Lateral ventricle
13,96 ± 5,58
11,07 ± 6,62
< 0,05
Third ventricle
1,09 ± 0,37
0,80 ± 0,34
< 0,01
Fourth ventricle
1,62 ± 0,34
1,52 ± 0,49
> 0,05
The results showed that the volume of lateral ventricular and
third ventricular in the depressive patient group, is statistically
significant p <0.05.


9
Table 3.18. Hippocampus volume in the studied patient group
Disease group
Symptom group
Brain structure
(n = 32)

(n = 41)
p
volume (cm3)
X ± SD
X ± SD
Right hippocampus
3,99 ± 0,77
4,41 ± 0,40
< 0,01
Left 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 cm 3) was smaller than the
whole hippocampus volume in the symptom group (8.88 ± 0.85 cm3)
is statisticalaly significant p <0.001.
Table 3.19. Volume of caudatennucleus in the studied patient group
Disease group Symptom group
Brain structure
volume

(n = 32)

(n = 41)

p

(cm3)
X ± SD
X ± SD
Right caudatennucleus
3,31 ± 0,44
3,45 ± 0,51
> 0,05
Left caudatennucleus
3,16 ± 0,42
3,55 ± 0,48
< 0,01
Bilateral audatennucleus
6,47 ± 0,86
7,00 ± 0,96
< 0,05
The results showed that the volume of caudatennucleus in the
depression group (6.47 ± 0.86 cm3) was smaller than one in the
symptom 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


10
Group
Serotonin

(ng/ml)

Severe symptom
Median (TPV 25; 75)

Symptom
Median (TPV 25; 75)

p (b)

84,17 ± 82,02
125,24 ± 118,51
< 0,05
57,35(18,46; 126,82)
85,58 (31,05; 189,29)
(n = 72)
(n = 68)
2,11 ± 1,13
6,34 ± 2,86
< 0,001
CSF
2,02(1,37; 2,86)
6,09(4,27; 7,81)
(n = 36)
(n = 32)
(b)
: Mann-Withney U. Test. The results showed that Serotonin
concentration in PL and in CSF in severe depression disorder patients
were 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
Group
Severe symptom
Symptom
Serotonin
p (b)
Median
(TPV
25;
75)
Median
(TPV
25;
75)
(ng/ml)
71,94 ± 69,30
92,21 ± 96,32
> 0,05
Male
54,17(18,27; 98,17)
44,61(21,53; 157,79)
(n = 35)
(n = 41)
PL
75,74 ± 91,91

175,39 ± 132,60
< 0,01
Female
83,30(17,16; 148,99)
159,09(64,26; 234,07)
(n = 37)
(n = 27)
2,18± 1,06
5,99 ± 2,67
< 0,001
Male
2,25(1,41; 2,89)
5,80(4,02; 7,09)
(n = 23)
(n = 24)
CSF
1,98 ± 1,27
7,37 ± 3,16
< 0,01
Female
1,60(1,22; 2,71)
7,92(5,160; 9,50)
(n = 13)
(n = 8)
The results showed that serotonin concentration in
cerebrospinal fluid in male patients with severe depression disorder
PL


11

was much lower than the symptom group, with p <0.001. serotonin
concentration in cerebrospinal fluid in female patients with severe
depression 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);

Emotional disorder

Indicator

p

Nervous, scared

Decreased
serotonin in PL

Yes
n

No.
%

n

0,5 (0,20 –
%

≤ 80 ng/ml

28

52,8

14

73,7

> 80 ng/ml

25

47,2

5

26,3

p > 0,05

Unstable emotion

Decreased
serotonin in PL

≤ 80 ng/ml

1,24);
(c)

Yes

No

0,29 (0,09 -

n

%

n

%

0,92);

25

55,4

17

77,3

p(c) < 0,05

> 80 ng/ml
25
44,6
5
22,7
2
(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.
(c)


12
Table 3.28. The rate of change in Serotonin concentration in plasma
with paranoia
Group
OR (95%,CI);
Disorder of thinking
Indicator
p
Obsessive seriously ill
Decreased
serotonin in PL
Yes
No.
0,89 (0,34-2,30);
n

%
n
%
p(c) > 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
6
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 <0.05.
Table 3.32. The rate of change in Serotonin concentration in plasma, cerebrospinal
fluid with suicidal behavior
Without
Suicidal
Suicidal
Group
OR (95%,CI);
behavior
behavior
Indicator
p(c)
n
%
n
%
Decreased ≤ 80 ng/ml
8
50,0 34 60,7
0,65
serotonin
(0,21-1,98);

in PL
> 80 ng/ml
8
50,0 22 39,
p(c) > 0,05
Decreased ≤ 1,6 ng/ml
15,75
6
85,7 8
27,6
serotonin
(1,63-152,18);
> 1,6 ng/ml
1
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 <0.01.


13
Table 3.34. A multivariate regression relationship was found between
a reduced serotonin concentration in plasma and some clinical
symptoms in severe depression patients
Probability associated with
reduced serotonin

Correlation coefficient R2

concentration in plasma
68,1%
Factor

OR

0,227 (R= 0,48)
Confidence

p
< 0,001

p
interval (95%, CI)
Self-charged paranoia
0,31
0,09 –1,09
0,068
Unstable emotion
0,24
0,06 – 0,92
0,038
Poor coward, inferior thought
2,54
0,22 – 29,68
0,457
Unhappy idea
0,27

0,08 – 0,89
0,032
Suicidal behavior
0,75
0,21 – 2.60
0,65
The results showed a positive correlation between the
reduced serotonin PL ≤ 80 ng/ml with some clinical symptoms with
R = 0.48; p <0.05


14
Table 3.36. Associated multivariate regression between reduced
serotonin concentration in cerebrospinal fluid and some clinical
symptoms in severe depression patients
Probability associated with
reduced serotonin concentration

Correlation coefficient R2

in cerebrospinal fluid
75,0%
Factor

OR

0,304 (R=0,551)
Confidence

p

< 0,001

p
interval (95%, CI)
Self-charged paranoia
0,79
1,03 –6,17
0,829
Unstable emotion
1,65
0,28 – 9,6
0,579
Poor coward, inferior thought
0,71
0,05 – 10,24
0,798
Unhappy idea
1,88
0,34 – 10,379
0,47
Suicidal behavior
14,81
1,31 – 168,13
0,03
The results showed a positive correlation between the
reduced serotonin in Poor coward, inferior thought ≤ 1.6 ng/ml and
clinical symptoms in severe depression patients with R = 0.551 and p
<0.001. Among the symptoms associated with reduced serotonin
concentration in CSF, suicidal behavior was closely related in
depression disorder patients with OR (95%, CI) of 14.81 (1.31 168.13), p <0.05.

15
3.5. The relationship between the volume of some brain
structures and some clinical symptoms in severe depression
patients
Table 3.37. Associated multivariate regression between self-charged
paranoid symptoms and some brain structures on MRI in depressive
patients
Probability associated
with self-charged
Correlation coefficient R2
P
paranoia
71,9%

0,403 (R= 0,635)

< 0,001

Confidence interval
P
(95%, CI)
Intracranial volume
0,98
0,95 –1,01
0,141
Triple ventricular volume 41,71
0,57 – 303,62
0,088

Frontal lobe volume
1,06
0,95 –1,18
0,310
Hippocampus volume
26,85
1,18 – 611,76
0,039
Caudatennucleus volume 0,183
0,021 – 1,576
0,122
Corpus callosum
13,81
0,69 – 277,55
0,086
There was a strong correlation between self-charged paranoid
symptoms and the volume of some upper brain structures, with R =
0.635; p <0.001.
Table 3.38. Multivariate regression relationship between suicidal
intent and the volume of some brain structures on MRI in severe
depressive patients
Probability associated with
Correlation coefficient R2
P
self-charged paranoia
71,9%
0,377 (R= 0,614)
< 0,001
Confidence interval
Factor

OR
P
(95%, CI)
Intracranial volume
1,01
0,99 –1,03
0,232
Triple ventricular volume
1,43
0,01 – 178,14
0,884
Frontal lobe volume
0,94
0,83 –1,06
0,316
Hippocampus volume
2,46
0,41 – 14,68
0,323
Caudatennucleus volume
0,35
0,08 – 1,58
0,170
Corpus callosum
0,09
0,01 – 1,03
0,053
Factor

OR

16
The results showed a high correlation between suicidal intent
symptoms and the volume of some brain structures on MRI with R =
0.614; p <0.001.
Table 3.39. Multivariate regression relationship between suicidal
behavior with the volume of some brain structures on MRI in severe
depression patients
Probability associated with
Correlation coefficient R2
P
suicidal behavior
81,3%
0,259(R= 0,509)
< 0,001
Confidence interval
Factor
OR
P
(95%, CI)
Intracranial volume
0,98
0,95 –1,01
0,162
Triple ventricular volume
62,96
0,52 – 760,41
0,090
Frontal lobe volume

1,11
0,96 –1,29
0,171
Hippocampus volume
3,96
0,31 – 50,08
0,288
Caudatennucleus volume
0,44
0,06 – 3,22
0,419
Corpus callosum
12,80
0,71 – 230,40
0,084
The results showed a correlation between suicidal behavior
and the volume of some brain structures on MRI in patients with R =
0,509; p <0.001.


17
Table 3.41. Multivariate regression relationship between psychotic
symptoms and volume of some MRI brain structures in severe
depression patients
Probability associated
Correlation coefficient R2
P
with psychotic symptom
71,9%
0,367 (R= 0,606)

< 0,001
Confidence interval
Factor
OR
P
(95%, CI)
Intracranial volume
0,97
0,95 –0,99
0,024
Triple ventricular volume
7,26
0,25 – 212,85
0,250
Frontal lobe volume
1,05
0,96 –1,16
0,275
Hippocampus volume
11,92
1,03 – 138,06
0,047
Caudatennucleus volume
2,11
0,47 – 9,59
0,333
Corpus callosum
8,66
0,80– 93,85
0,076

The results showed a close correlation between psychotic
symptom and the volume of some brain structures with R = 0.606; p
<0.001.
Table 3.42. Multivariate regression relationship between duration of
illness > 2 years and volume of some brain structures on MRI in
severe depression patients
Probability associated with
Correlation coefficient R2
P
duration of illness> 2 years
90,6%
0,528 (R= 0,727)
< 0,001
Confidence interval
Factor
OR
P
(95%, CI)
Intracranial volume
0,98
0,96 –1,01
0,153
Triple ventricular volume
241,92
1,69 – 3457,60
0,030
Frontal lobe volume
1,23
1,03 –1,46
0,020

Hippocampus volume
0,71
0,13 – 3,75
0,706
Caudatennucleus volume
0,24
0,03 – 1,85
0,243
Corpus callosum
1,10
0,11 – 11,42
1,102
The results showed a strong correlation between duration of
illness > 2 years and the volume of some brain structures on MRI in
severe depression disorder patients with with correlation coefficient
R = 0.727; p <0.001.


18
CHAPTER 4
DISCUSSION
4.3. Morphological characteristics of some brain structures in
severe depression patients
- Intracranial volume and frontal lobe volume in severe
depression patients
The results of Table 3.15 show that the intracranial volume and
frontal lobe volume in the group of severe depression patients are
1422,09 ± 128,60 cm3; 161,82 ± 18,45 cm3, smaller than the of in the
control group 1520,36 ± 131,14 cm3, 168,80 ± 20,73 cm3, this
difference is statistically significant p < 0,05. Bromis K et al. (2018)

Bromis K et al (2018) have shown a decrease in brain volume,
intracranial volume, prefrontal brain and hippocampus volume in
patients at high risk of depression. Lin C et al. (2017) have shown
that the reduction of gray matter in patients with severe depression
not only occurs in the prefrontal brain, hippocampus, but also in the
upper temporal lobe, the right temporal lobe, and the Insula lobe.
- Brain ventricular volume in severe depression patients
Table 3.16 shows that the ventricular volume in the depression
patient group is greater than the control group, especially the lateral
ventricles and the third ventricle in the depression patient group
(13,66 ± 5,29 cm3 and 1,05 ± 0,31 cm3, respectively), larger than
volume of the lateral ventricles and the third ventricle volume in the
control group (11,07 ± 6,62 cm3 and 0,80 ± 0,34 cm3, respectively),
has statistical significance with p < 0,05. Thus, the ventricular
volume in patients with severe depression is greater than that in
normal people. This proves that there is expansion of ventricles in
severe depression patients. It is consistent with the recent studies of
the authors when studying CT and MRI images showed the brain
ventricles and expansion gap in depression patients, especially in the
elderly. Hendrie C.A and Pickles A.R (2010) suggest that depression


19
originates in the third ventricle, changes in this area will affect the
circadian rhythms, the appetite, sexual ability and fear/anxiety
response of the patient. The third ventricule volume has a clear
change in depression disease.
- Hippocampus volume and nucleus caudatus volume in
severe depression patients
The total hippocampus volume in the depression patient group

(7,99 ± 0,77 cm3) is smaller than the total hippocampus volume in the
control group (8,88 ± 0,85 cm3), it has statistical significance with p
< 0,001. The volume of the nucleus caudatus in the depression patient
group (6,47 ± 0,86 cm3) is smaller than the volume of the nucleus
caudatus in the control group (7,00 ± 0,96 cm3), it has statistical
significance with p < 0,05. Yukel D et al. (2018) has found that there
was a reduction in gray matter volume in the limbic region.
Especifically, brain volume reduction was measured and identified in
areas including hippocampus, prefrontal cortex, thalamus opticus,
nucleus caudatus and striae. Sivakumar P.T. et al. (2014) studying
hippocampus area by cranial MRI scan of 25 patients with delayed
onset depression found that hippocampus weight of depression
patients was lower than that of healthy people (1.01 ± 0.19 ml
compared to 1.16 ± 0.25 ml).
4.4. Serotonin PL and CSF concentrations in severe depression
patients
- Serotonin PL and CSF concentrations in severe depression
patient group (84,17 ± 82,02 ng/ml and 2,11 ± 1,13 ng/ml,
respectively) is much lower than that of the control group (125,24 ±
118,51 ng/ml and 6,34 ± 2,86 ng/ml, respectively), the difference is
statistically significant with p < 0,05 and p < 0,001. According to
Sadock B.J. (2015), serotonin concentration and their metabolites in
cerebrospinal fluid and plasma were significantly lower than that of
normal people.


20
- The reduction rate of serotonin CSF ≤ 1,6 ng/ml in the severely
depressive disorder group (38,9%) is much higher than that of the
control group (3,1%), it has statistical significance with OR = 19,73

(2,41-161,26), p < 0,001. According to Asberg M et al. (2003),
depression patients with serotonin CSF levels < 1,6 ng/ml had higher
risk of suicidal behavior than depression patients with high levels of
serotonin CSF. This result is consistent with the judgment of Mann
J.J. (1999) studying in 347 patients, most of whom were severe
depressive, had suicidal behavior that were associated with low
serotonin levels in CSF.
- Serotonin CSF level in male patients with severe depressive
disorders is much lower than that in the control group, with p <
0,001. Serotonin PL and CSF levels in female patients with severe
depression are much lower than that in female of the control group,
withp < 0,01. It is consistent with the studies of Saldanha B.D et al
(2009), Gao H.Q et al (2008) and Stanley B. (2000).
4.5. Relationship between serotonin PL, CSF levels and the
volume of some brain structures with some clinical symptoms in
severe depression patients.
4.5.1. Relationship between serotonin PL, CSF levels with some
clinical symptoms in severe depression patients.
- Serotonin PL levels in the group without emotional instability
(77.3%) were higher than those in the group with emotional stability
(50,0%), with OR = 0,29 (0,08-0,92); p < 0,05. Serotonin PL levels
were higher in patient group without paranoid symptom of selfaccusation (65.5%) than that with paranoid symptom of selfaccusation (35.3%), with OR = 0,29 (0,09 – 0,90); p < 0,05. This suggests
that the classification of ICD-10 and DSM-5 for severe depression
without psychosis and severe depression with psychosis are of
practical significance. Gelder M. (2010), Sadock B.J. (2015) both
believe that depression with psychosis is synonymous with paranoid
depression.


21

- Serotonin CSF levels ≤ 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 < 0,01. The relationship between
suicidal behavior and serotonin levels of cerebrospinal fluid in
depression has been mentioned by many authors such as: Miler J.M.
(2013); Mann J.J. (2013); Ruljancic N et al (2013).
- There was a positive correlation between a reduction in
serotonin PL ≤ 80 ng/ml with age, gender and number of
hospitalizations ≥ 2 and duration of illness ≥ 2 years with correlation
coefficient r = 0.464; p <0.001 and a positive correlation between a
reduction in serotonin CSF ≤ 1,6 ng/ml with age, gender and number
of hospitalizations ≥ 2 and duration of illness ≥ 2 years with
correlation coefficient R = 0,537 (p < 0,05).
- There was a positive correlation between a reduction in
serotonin PL ≤ 80 ng/ml and some clinical symptoms with R = 0,48;p
< 0,05 and a positive correlation between a reduction in serotonin
CSF ≤ 1,6 ng/ml and some clinical symptoms in severe depression
patients with R = 0,551 and p < 0,001.
These results indicate that these factors have a clear influence on
the progression and prognosis of depression. These factors are
consistent with the prognostic factors of many authors such as Gelder
M. (2010), Sadock B.J. (2015) in depression.
4.5.2. The relationship between the volume of some brain
structures and some clinical symptoms in severe depression
patients.
- There was a strong correlation between paranoid symptoms of
self-accusations and the volume of some of the upper brain
structures, with R = 0,635; p < 0, a strong correlation between
psychotic symptoms and the volume of some brain structures with r =
0,606; p < 0,001. Especially the hippocampus volume is most closely

related. In depression patients with psychosis, it appears cerebral
atrophy in the two spheres, ventricular dilatation, left temporal lobe


22
atrophy. Besteher B. (2019), regarding to hippocampus volume in
depression patients, has found a positive correlation between left
hippocampus volume and clinical symptoms of depression patients.
Lee B et al. (2019) has shown that there is a relationship between
clinical characteristics and changes in volume of some brain
structures in depression patients.
- There was a high correlation between intention and suicidal
behavior with the volume of some brain structures on MRI and the
respective correlation coefficient of R = 0,614; p <0.001 and R =
0.50; p <0.001. Maria AO et al. (2016) suggests that in the higherlevel brain, raphe having the serotonin 1A BPF suitable for lower
levels of discharging and releasing serotonin neurons and caused a
weakened serotonin signaling model that leads to suicidal intention
and having suicidal behavior of higher risk of death. Miler J.M.
(2013) used PET-CT scan method to determined the serotonin
transporter ability in the brain on 51 severe depression patients
according to DSM-IV, the author found that severe depression
patients with suicidal behavior had lower serotonin transporter links
in the middle brain than those without depression (p = 0.031).
- There was a strong correlation between the duration of illness >
2 years and the volume of some brain structures on MRI in patients
with severe depressive disorders with the correlation coefficient R =
0.727; p <0.001. Our findings are consistent with the findings of
Hendrie C.A and Pickles A.R (2010) when supposing that depression
is highly related to the third ventricle, changes in this area shall affect
the circadian rhythm, the appetite, sexual ability and fear/anxiety

response of the patient. The third ventricule volume has a clear
change in depression.


23
CONCLUSION
Studying morphological characteristics of some brain
structures and serotonin concentration in plasma and cerebrospinal
fluid in 72 patients diagnosed with severe depression, inpatient
treated in the Department of Psychiatry - Military Hospital 103 from
May 2015 to June 2018, we have drawn some conclusions:
1. Several clinical characteristics in severe depression patients
- The common age is ages > 45 (38.89%).
- Symptoms of depression: decreased mood (100%), decreased
interest and hobbies (100%), fatigue (98.6%), anorexia (100%),
insomnia (97.2%),
pessimism (98.6%), reduction in labor
productivity (97.2%), paranoia is guilty (23.6%), rough
hallucinations (26.4%).
- The proportion of patients with suicidal intention (68.1%) and
self-suicidal behavior (22.2%).
2. Morphological characteristics of some cerebral structures and
serotonin concentration in plasma and cerebrospinal fluid
concentration in severe depression patients
2.1. Morphological characteristics of some brain structures in
severe depression patients
- The intracranial volume and frontal lobe volume (1422.09 ±
128.60 cm3 and 158.93 ± 21.98 cm3) in severe depression patients
are smaller than that of normal people (1520.36 ± 131.14 cm3 and
168.80 ± 20.73 cm3), with p < 0,05

- The third ventricule and lateral ventricles in patients with severe
depression are expanded wider than normal people with p < 0.05.
- The hippocampus volume, caudal nucleus volume in patients
with severe depression is smaller than that of normal people, with p <
0.001 and p < 0.05.
2.2. Serotonin PL and serotonin CSF levels in severe depression
patients
- Serotonin PL and CSF levels in the patient group (84.17 ± 82.02
ng/ml and 2.11 ± 1.13 ng/ml) were much lower than those of the
control group (125.24 ± 118.51 ng/ml and 6.34 ± 2.86 ng/ml), with p
< 0.001. PL serotonin levels in the depression group without