Study on the relationship between serotonin plasma and cerebrospinal fluid concentrations and clinical symptoms in severe depression patients

To study the relationship between serotonin plasma and cerebrospinal fluid concentrations and clinical symptoms in patients with severe depression. Subjects and methods: Descriptive and cross-sectional studies.

STUDY ON THE RELATIONSHIP BETWEEN SEROTONIN PLASMA AND CEREBROSPINAL FLUID CONCENTRATIONS AND CLINICAL SYMPTOMS IN SEVERE DEPRESSION PATIENTS

Do Xuan Tinh 1 ; Cao Tien Duc 1 ; Nguyen Linh Toan 2

SUMMARY

Objectives: To study the relationship between serotonin plasma and cerebrospinal fluid concentrations and clinical symptoms in patients with severe depression Subjects and methods: Descriptive and cross-sectional studies This study was carried out on 72 patients with severe depression treated at the Department of Psychiatry, 103 Military Hospital from June

2016 to June 2018 Peripheral blood and cerebrospinal fluid samples of patients were collected for measurement of serotonin concentrations Some clinical symptoms of patients were also determined Results: There were correlations between decreased serotonin plasma (R = 0.452;

p < 0.001) and cerebrospinal fluid concentrations (R = 0.534; p < 0.001) with the appearance of clinical features (age, male and number of hospitalizations ≥ 2 times and duration of illness

≥ 2 years), clinical symptoms (paranoia, emotional instability, low self-esteem and inferiority, unfortunate thoughts, suicidal behavior; R = 0.48; p < 0.001) in severely depressed patients; especially patients aged ≥ 45 years and male, having unfortunate ideas and unstable emotions Severe depression patients with suicidal behavior had a lower proportion of serotonin cerebrospinal fluid concentrations of ≤ 1.6 ng/mL (85.7%) than those without suicidal behavior (27.6%), p < 0.01 Conclusion: Serotonin plasma and cerebrospinal fluid concentrations were associated with the appearance of clinical features, clinical symptoms, in patients with severe depression, especially those gender, unstable emotions, unhappy idea and suicidal behavior

* Keywords: Severe depression; Clinical symptoms; Serotonin concentration

INTRODUCTION

Serotonin is a neurotransmitter that

plays an important role in depression,

both as a cause and a consequence of

depression A serotonin deficiency in the

sinap cleft is considered a major cause of

depression [1, 3, 4]

The study on changes in serotonin

concentration related to depressive patients

has been analyzed, commented and

confirmed by authors who showed that

there was decrease of serotonin concentration in depressed patients Sadock B.J (2015) suggested that the lower the serotonin concentration in the sinap cleft, the worse the depression was [4].Numerous studies have demonstrated that the decrease in serotonin levels in the brain of depressed patients is very clear, even very low, only about 30% of the average person and the corresponding severity or mild of depressed patients

[5, 6]

1 103 Military Hospital

2 Vietnam Military Medical University

Corresponding author: Do Xuan Tinh (doxuantinhbv103@gmail.com)

Date received: 18/10/2019 Date accepted: 21/11/2019

In Vietnam, there had been some researches

on plasma serotonin concentration in

depression, there has been no researches

on serotonin changes in cerebrospinal

fluid Since then, we have conducted the

research with the aim: Study on the

relationship between plasma and cerebrospinal

fluid serotonin concentrations and clinical

symptoms in patients with severe depression

SUBJECTS AND METHODS

1 Subjects

A study of 72 patients diagnosed with

severe depression, inpatient treatment at

the Department of Psychiatry, 103 Military

Hospital from June 2016 to June 2018

* Selection criteria: According to the

standard of the 10th International Classification

of Diseases (ICD-10) on mental and behavior

disorders of WHO (1992), section F32

* Exclusion criteria: Patients with

general body conditions that were related

to the risk of lowering plasma serotonin

concentration such as gastrointestinal,

peripheral neuropathy, endocrine system

diseases, heart diseases…

2 Methods

A prospective, cross-sectional study,

and case-by-case analysis of individual

case histories All patients were clinically

examined and blood tested to quantify

serum serotonin concentration, 36 patients

underwent lumbar puncture to get

cerebrospinal fluid

Time of serotonin quantitative sampling:

Patients in the acute phase, after admission

from the 1st to 7th day Blood sampling

time was from 6 - 7 am daily; lumbar

puncture sampling of cerebrospinal fluid

concentrations from 8 - 9 am daily Centrifuge plasma, store at -80oC until the test

Quantitative serotonin test by ELISA was conducted at the Department of Pathophysiology, Military Medical University The unit of serotonin is ng/mL

The criteria for the diagnosis of the severe depression stage following the diagnostic criteria of ICD-10F (1992), section F32 [3] were described with the following symptoms:

- Main symptoms:

+ Mood decreases

+ Losing interest, enjoying

+ Reducing energy, easily tired

- Common symptoms:

+ Decreased attention span; reduced self-esteem and confidence

+ There are ideas of being guilty and unworthy; looking at the gloomy and pessimistic future ideas and acts of self-destruction or suicide; sleep disorders; less appetite eating

These conditions usually last at least

2 weeks When severe depression often has common body symptoms: Weight loss, decreased exercise capacity, stupor, constipation, diarrhea, cardiovascular disorders

Data were processed by using SPSS

20 software Evaluate the correlation between changes in plasma serotonin concentration and cerebrospinal serotonin with control group and some clinical manifestations by OR (Odds ratio) with 95% confidence interval (95%CI)

RESULTS AND DISCUSSION

1 Relationship between plasma serotonin concentration and cerebrospinal fluid with some characteristics of patients with severe depression

In this study, we selected the plasma serotonin level ≤ 80 ng/mL and the cerebrospinal fluid serotonin ≤ 1.6 ng/mL to find the correlation and the relationship of serotonin with clinical features in the severe depression disease based on previous studies of plasma serotonin and cerebrospinal fluid serotonin in depressed patients, healthy non-depressed patients, and pathogenesis studies [5, 9, 10]

Table 1: Relationship between decreased serum serotonin concentration (≤ 80 ng/mL)

and a feature in severely depressed patients

Correct prediction of reduced

2

p

The results showed a correlation between plasma serotonin reduction (≤ 80 ng/mL) and the appearance of clinical features in patients with severe depression: age, male and number of hospitalizations ≥ 2 times and duration of illness ≥ 2 years with a correlation coefficient R = 0.452 (p < 0.001); of which gender was closely related to decreased plasma serotonin concentration

Table 2: Relationship between serotonin cerebrospinal fluid concentration (≤ 1.6 ng/mL)

and clinical features in severely depressed patients

Correct prediction of decreased

2

p

The results showed a strong correlation

between the decrease in cerebrospinal

fluid serotonin concentration (≤ 1.6 ng/mL)

and the combination of characteristics of

severe depression patients such as age,

male and hospitalizations ≥ 2 times and

illness duration ≥ 2 years with correlation

coefficient R = 0.534 (p < 0.001); in which

patients in the age group > 45 years old

and male gender were closely related to

decreased cerebrospinal fluid serotonin

concentration

Many studies showed that factors such

as age, gender, number of hospitalizations ≥

2 times, duration of disease ≥ 2 years

were clinical characteristics of patients

with severe depression Kaplan H.I (1994)

stated that depression was 2 - 3 times

more common in women than in men, and

the rate of depressive disorders increased

by age group, which was the highest in the age group of 45 - 65 [2] Bui Quang Huy (2016) chose a disease landmark for more than 2 years to decide whether the patients needed lifelong reinforcement or not [1] The research results showed that serum serotonin and cerebrospinal fluid concentration played an important role in the clinical characteristics of patients with severe depression These factors were consistent with the prognostic factors of many authors such as Gelder M (2010), Sadock B.J (2015) in depression when multiple clinical symptoms appeared [3, 4] It can be said that severe depression patients were older than 45 years old or that group of decreased cerebrospinal fluid serotonin

2 Relationship between plasma serotonin and cerebrospinal fluid concentrations and clinical symptoms in patients with severe depression

Table 3: Relationship between decreased serum serotonin concentration (≤ 80 ng/mL)

and the appearance of clinical symptoms in severely depressed patients

Correct prediction of reduced plasma

The results showed a correlation between decreased plasma serotonin concentration (≤ 80 ng/mL) and the appearance of clinical symptoms: Self-accusatory paranoia, emotional instability, inferiority and inferiority, unfortunate ideas, suicidal behavior with correlation coefficient R = 0.48 (p < 0.05); in which the group having unfortunate ideas and unstable emotions had a strong correlation to decreased plasma This means that clinical symptoms also have different values in diagnosing and assessing the severity

of depression

This result was consistent with the diagnostic criteria of both ICD-10 and DSM-5 disease classification systems, which required the main symptoms and some or all of the dialectic symptoms to diagnose severity depression The recent research by Wayne C.D et al (2007) used PET and [carbonyl - 11 C] WAY-100635 (5-HT1A R selective radioactive PET method for pre-5-HT1A R bond first and after synaptic) to study the 5-HT1A R receptor (serotonin 1A receptor) in 16 subjects with severe depression and 8 healthy controls, the results showed that 5-HT1A R decreased 26% in the Mussels (mesiotemporal cortex-MTC) (p < 0.005) and 43% in the gray core in severe depression compared to the prospective group (p < 0.001) and were closely related to 5-HT1A R reduction in depressed patients suicidal behavior [8]

Table 4: Relationship between decreased cerebrospinal fluid serotonin concentration

(≤ 1.6 ng/mL) and clinical symptoms in severely depressed patients

Correct prediction of reduced

cerebrospinal fluid serotonin Correlation coefficients R

The results showed a strong correlation between the decrease in cerebrospinal fluid serotonin concentration (≤ 1.6 ng/mL) and the appearance of clinical symptoms in severely depressed patients such as self-accusatory delusions and unstable feeling, inferiority, unhappy idea, suicidal behavior In which, there was suicidal behavior closely associated with decreased cerebrospinal fluid serotonin

Table 5: The change rate of reduction on serotonin serum and cerebrospinal fluid

with psychotic symptoms in patients with severe depression

Patients with psychosis Patients without psychosis Group

Plasma serotonin

Cerebrospinal

serotonin ≤1.6 ng/mL

The results showed that the proportion

of the group with reduced serotonin plasma

level ≤ 80 ng/mL without psychosis (70.7%)

was higher than the psychotic group (41.9%),

the difference was statistically significant

with OR = 0.30 (95%CI: 0.11 - 0.80);

p < 0.05 Whereas in patients with psychosis,

the rate of serotonin reduction in

cerebrospinal fluid was higher than in the

group without psychosis but the difference

was not statistically significant with p > 0.05

Our results showed that psychotic

symptoms were not associated with

serotonin concentration in both plasma

and cerebrospinal fluid This result was

inconsistent with other studies

Heng-Qiang Gao et al (2008) showed a correlation

between plasma serotonin and cerebrospinal serotonin in depressed patients Study of post-stroke depression patients, there was

a good correlation between serum serotonin concentration and cerebrospinal serotonin with correlation coefficient R = 0.664 (p < 0.001) and plasma serotonin concentration

in some clinical symptoms substitutes for cerebrospinal fluid serotonin levels in the monitoring of depressed patients [5] In the author’s study, serotonin concentration was lower than both in cerebrospinal fluid and plasma in depressed patients with psychosis This may explain that our studied patients were still low, not enough to prove the correlation between serotonin and psychotic symptoms

Table 6: The change rate in the plasma serotonin concentration, cerebrospinal fluid

with suicidal behavior in patients with severe depression

Suicidal behavior No suicidal behavior Group

Plasma serotonin

Cerebrospinal

serotonin ≤ 1.6 ng/mL

The results showed that patients with

severe depression had a higher proportion

of the group with decreased serotonin

cerebrospinal fluid concentrations ≤ 1.6 ng/mL

(85.7%) compared to the group without

suicidal behavior (27.6%), the difference

was statistically significant with p < 0.01

Similar to the study by Ruljancic N et al (2013) on serotonin concentration in platelets

in 79 depressed suicidal patients and

101 depressed non-suicidal patients compared with 77 healthy subjects had been shown that serotonin concentration

in platelets of depression group with and

without suicidal behavior was lower than

that of control group [6] Maria A.O et al

(2015) suggested that the severity of

suicidal intent in severe depression was

related to the brain and serotonin 1A BP F

frontal region and lower serotonin release

at key projection sites of the brain, such

as the anterior region, may be the main

cause of suicidal intent and, more serious,

suicidal behaviors that cause high death

for patients such as cutting blood vessels,

jumping into wells, and strangulation,

drinking poison, jumping on the floor [7]

CONCLUSION

By studying the correlation between

changes in plasma serotonin concentration

and cerebrospinal fluid with clinical

characteristics in patients with severe

depression, we found:

- There were correlations between

decreased serotonin plasma (R = 0.452;

p < 0.001) and cerebrospinal fluid

concentration (R = 0.534; p < 0.001) with

the appearance of clinical features in

patients with severe depression: age, male

and number of hospitalizations ≥ 2 times

and illness duration ≥ 2 years; in which

the occurrence of patients ≥ 45 years old

and male gender was strongly associated

with decreased plasma serotonin or

cerebrospinal fluid concentration

- There were correlations between

decreased serotonin serum (R = 0.48;

p < 0.001) and cerebrospinal fluid

concentration (R = 0.551; p < 0.001) with

the appearance of clinical symptoms:

Self-paranoid paranoia crime, unstable emotions, inferiority thoughts, unhappy ideas, suicidal behavior; in which the group having unfortunate ideas and unstable emotions had a strong correlation

to decreased plasma OR (95%CI) plasma concentrations of 0.27 and 0.24, respectively, with p < 0.05

- Severe depression patients with suicidal behavior had a lower proportion of serotonin cerebrospinal fluid concentrations of

≤ 1.6 ng/mL (85.7%) than those without suicidal behavior (27.6%), p < 0.01

Thus, plasma serotonin and cerebrospinal fluid concentration are associated with the occurrence of clinical features and symptoms

of patients with severe depression, especially those gender, unstable emotions, unhappy idea and suicidal behavior

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