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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 45  |  Issue : 4  |  Page : 213-219

Serum serotonin as a potential risk factor in female suicide attempts by poisoning, in different menstrual cycle phases


1 Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Tanta University, Tanta, Egypt
2 Department of Neuropsychiatry, Faculty of Medicine, Tanta University, Tanta, Egypt

Date of Submission01-Mar-2017
Date of Acceptance01-Jun-2017
Date of Web Publication12-Mar-2018

Correspondence Address:
Aisha E.A Fattah El-Mihy
Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Tanta University, Tanta, Mostafa Kamel Street, Borg El-Kasaby, 6843
Egypt
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DOI: 10.4103/tmj.tmj_28_17

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  Abstract 


Background Suicide is a major public and mental health concern worldwide today. It lies behind exceeding numbers of deaths every year. This necessitates studying the causes and risk factors involved in suicidal behavior. Suicide attempts are found to be more common in women, with higher risk during the low estrogen phases of the menstrual cycle. Serotonin is a neurotransmitter that is proved by many studies to be involved in suicidal behavior. A relation between circulating estrogen levels and serotonergic function is supposed by some studies to explain the link between female suicide attempts and low estrogen phases of the menstrual cycle.
Aim The aim of this work was to study serum serotonin level as a potential risk factor in female suicide attempts in the different menstrual cycle phases. Also, this study aimed to investigate the potential correlation between serum serotonin and estrogen levels.
Patients and methods This cross-sectional study was carried out on two groups: the suicidal group that included women with suicide attempts who came to Tanta Poison-Control Center during the period from the beginning of July 2015 to the end of December 2015, and the control group that included 25 nonsuicidal apparently healthy female volunteers. The menstrual cycle phase was assessed for those women; the serum serotonin level was estimated by specific ELISA techniques, and the suicidal intent of the suicidal group was assessed by Pierce’s suicidal intent scale.
Results and conclusion This study demonstrated that the suicide attempters had significantly lower serum serotonin levels. This significance was observed to be in the menstrual and the whole luteal phases. A significant inverse correlation was found between serum serotonin levels and Pierce’s suicidal intent scale for the women who attempted suicide in the late luteal and menstrual phases. Also, a significant positive correlation was found between serum estrogen and serotonin levels.

Keywords: menstrual, serotonin, suicide


How to cite this article:
Kabbash AM, Ramadan ES, El-Fotoh Abo El-Wafa AM, Fattah El-Mihy AE. Serum serotonin as a potential risk factor in female suicide attempts by poisoning, in different menstrual cycle phases. Tanta Med J 2017;45:213-9

How to cite this URL:
Kabbash AM, Ramadan ES, El-Fotoh Abo El-Wafa AM, Fattah El-Mihy AE. Serum serotonin as a potential risk factor in female suicide attempts by poisoning, in different menstrual cycle phases. Tanta Med J [serial online] 2017 [cited 2018 Sep 22];45:213-9. Available from: http://www.tdj.eg.net/text.asp?2017/45/4/213/227116




  Introduction Top


Suicide is the deliberate act of ending one’s own life [1]. It is a major public and mental health concern in developed and developing countries today [2].

The WHO divides suicides into two categories: actual suicides and suicide attempts. Actual suicides are those that result in death, while suicide attempts are defined as ‘a self-destructive behavior with intent to end one’s life, independent of resulting damage’ [3].

According to the WHO, every year ∼1 000 000 people die by suicide. It is estimated that by 2020 this number will rise to 1 500 000 [4]. Self-inflicted death accounts for 1.5% of all deaths and is the 10th leading cause of death worldwide [5]. Egypt has one of the lowest suicide rates worldwide according to the latest available data from the WHO, as the mean standardized suicide rate was 0.2/100 000 for both sexes [4]. However, the official counts for the global burden of suicide are substantial underestimates especially in Islamic countries where suicide is prohibited [6].

Although there are no reliable statistical data on the incidence of suicide attempts, it is assumed that their number is several times that of completed suicides [7]. The crude rate of suicide attempts in Cairo was found to be 38.5/100 000. Depressive illnesses, hysterical reactions and adjustment disorders were found to be the main causes of the attempt. Overdose by tablet ingestion was the most commonly used method [8].

Suicide is a complex phenomenon involving many factors; sociodemographic, genetic, environmental, hormonal, and psychiatric. Each one of them contributes, to a different extent, in increasing the suicide risk of a particular individual at a given time period [9],[10],[11].

Women attempt suicide more than men do. Nearly 3–4 times as many women attempt suicide as men [12]. The risk of suicide and suicide attempts in women is proved to be higher during the low estrogen phases of the menstrual cycle, the late luteal (premenstrual) and menstrual phases [13],[14],[15],[16],[17],[18],[19]. Some studies have recently suggested that interaction between circulating estrogen and the serotonergic system may explain the increased risk of suicide attempts in low estrogen phases [14],[20].

Serotonin (5-hydroxytryptamine, 5HT) is involved in a wide variety of complex physiological, behavioral, and emotional processes [21]. Low brain serotonergic function appears to be undeniably related to suicidal behavior. Different elements of this complex system, including serotonin receptors, serotonin transporter and tryptophan hydroxylase have been researched in this respect [22]. The dorsal and the median raphe nuclei, which are the major collection of serotonin neurons in the brain, are proved to have altered serotonergic function in suicidal cases [21],[23],[24],[25]. The dorsal raphe also proved to contain estrogen receptors [26],[27]. Many studies in the literature suggest that during the hypoestrogenic period, lower brain serotonin levels are noted [23],[28],[29],[30],[31],[32],[33]. Also some studies have studied the relation between serum serotonin and serum estradiol levels [34],[35],[36],[37],[38]. Thus, low estradiol may contribute to decreased serotonergic neurotransmission, and this may underlie the link between menses and suicidal behaviors [20].


  Aim Top


The aim of this work is to study the serum serotonin level as a potential risk factor in female suicide attempts, in different menstrual cycle phases. Also, it aimed to investigate the potential correlation between serum serotonin and serum estrogen levels in those women.


  Patients and methods Top


Study design and sample selection

To achieve this goal, this cross-sectional study has been conducted over 6 months, from the beginning of July 2015 to the end of December 2015 on two groups: the suicidal group and the control group.
  1. The suicidal group included 48 women with suicidal attempts, who were referred to Tanta Poison-Control Center during the period of the study. The suicide attempt in this study was defined following the criteria of O’Carroll et al. [39] and Silverman et al. [40] as ‘a potentially self-injurious act with a nonfatal outcome, for which there is evidence of intent to die, that is, kill one-self’.
  2. The control group included 25 nonsuicidal apparently healthy female volunteers.


The inclusion criteria were (i) age between 15 and 60 years, (ii) the fertile females should have normal and regular menstrual cycles, and (iii) for the suicidal females, they should have been coming within 24 h of suicide attempts. The exclusion criteria were (i) history of menstrual irregularities, (ii) symptoms or signs suggesting ovarian failure, (iii) pregnant and lactating women, (iv) women on oral contraceptive pills (OCP) within the last 2 months or on hormonal replacement therapy, (v) ignorance about the first day of the last menstrual period, (vi) women on or suicidal by drugs or toxins affecting the serum serotonin level or hypothalamic–pituitary–gonadal axis, and (vii) coming more than 24 h after a suicide attempt (in the suicidal group) or history of previous suicide attempts (in the control group).

Subjects evaluation

The women of the two groups were evaluated as follows:
  1. History taking that included sociodemographic data, medication history, menstrual history that included asking the women about the characteristics of their menstrual cycles, especially in the last 6 months, including the regularity of cycles, length of cycle, duration of menstrual bleeding and the first day of the last menstrual bleeding.
  2. Analysis of the suicide attempt (in the suicidal group): included the method used for suicide, the duration that passed, the circumstances of the attempt and the history of previous suicide attempts. The intent to die was assessed using Pierce’s suicidal intent scale (PSIS) [41]. It consists of 12 questions and the possible total score ranges from 0 to 25, the higher the score the more the suicidal intent.
  3. Hormonal and serotonin measurements: 5 ml of venous blood was collected, under strict aseptic technique, and serum was separated for the estimation of levels of follicular-stimulating hormone, lutinizing hormone, estrogen, progesterone and serotonin using specific ELISA techniques. Blood samples from suicidal women were necessarily taken within 24 h of the suicide attempt.


The cycle phase at the day of suicide attempt (or the day of sample taking in the control group) was diagnosed by combining history and hormonal levels. Serum serotonin levels among suicidal women were studied in comparison to those among nonsuicidal ones. Also, the correlation between serum serotonin and estrogen levels was studied.

Statistical analysis

Statistical analysis of the data [42]

Data were fed to the computer and analyzed using IBM SPSS software package version 20.0 IBM (International Business Machines Corporation, Armonk, New York, United States) [43]. Qualitative data were described using number and percent. Quantitative data were described using range (minimum and maximum), mean, SD and median. Significance of the obtained results was judged at the 5% level. The used tests were: χ2-test, Fisher’s exact, Student’s t-test and Pearson’s correlation coefficient.

The research was approved by the Research Ethics Committee of the Faculty of Medicine, Tanta University.


  Results Top


From 1 July to the end of December 2015, and applying the inclusion/exclusion criteria of this study on the women who came to Tanta Poison-Control Center with intake of drug/poison in a suicide attempt; 48 women were included in the suicidal group. For each of these women, the menstrual cycle phase was determined, the suicidal intent was evaluated using PSIS and serum serotonin levels were studied in relation to the level of suicidal intent and in comparison with the control group. Also, the correlation between serum serotonin and estrogen levels was studied.

Twenty-five nonsuicidal apparently healthy female volunteers were selected as controls. Their ages ranged between 16 and 42 years (mean±SD=25.2±7.2 years). The women in the control group were selected to cover all phases of the cycle; that is, five in the menstrual phase, six in the follicular phase, three in the preovulatory (mid-cycle) phase, six in the early/mid-luteal phase, and five in the late luteal phase.

The sociodemographic data, educational and occupational status of the suicidal women are shown in [Table 1]. An analysis of the suicidal behavior is shown in [Table 2].
Table 1 Sociodemographic data, educational and occupational status of the suicidal women

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Table 2 Analysis of suicidal behavior in the suicidal women under study

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The suicidal intent in the suicidal women was assessed using PSIS; 34 women (70.8%) had high suicidal intent (i.e. score ≥10), 14 (29.2%) had moderate intent (score 4–9) and none had low intent (score ≤3) ([Table 2]).

By combining history and hormonal measurements, the cycle phase of the suicidal women at the day of the attempt was assessed; 12 women were found to be in the menstrual phase, 12 in the follicular phase, four in the preovulatory (mid-cycle) phase, nine in the early/mid-luteal phase and 11 in the late luteal (premenstrual) phase. None of these women was menopausal. The suicidal intent was more pronounced among women attempting suicide in the menstrual and late luteal phases than in women in other phases of the cycle ([Table 3] and [Table 4]).
Table 3 Pierce’s suicidal intent scale score of the suicidal attempters at different cycle phases

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Table 4 Pierce’s suicidal intent scale score in late luteal and menstrual phases versus the other cycle phases

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Comparison between suicidal and control groups regarding serotonin levels

Serum serotonin levels were compared between suicidal and control cases and the suicide attempters had significantly lower serum serotonin levels (P<0.001). This significance was only observed to be in the menstrual and the whole luteal phases ([Table 5] and [Table 6] and [Figure 1]).
Table 5 Comparison between the suicidal and control groups (in total), according to serotonin (ng/ml) levels

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Table 6 Comparison between the suicidal and control groups, according to serotonin (ng/ml) levels during each cycle phase

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Figure 1 Mean serotonin levels throughout the cycle phases (suicidal vs. control).

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Correlation between serum serotonin levels, Pierce’s suicidal intent scale scores and serum estrogen levels in the suicidal group

An inverse correlation was found between serum serotonin levels of the suicidal women and their PSIS scores. This inverse correlation was significant in the 23 women who attempted suicide in the late luteal and menstrual phases (r=−0.464, P=0.026) ([Table 7]). Also a significant positive correlation was found between serum estrogen and serotonin levels in all the 73 women studied (r=0.358, P=0.002) and in the 48 suicidal women (r=0.314, P=0.03) ([Table 8]).
Table 7 Correlation between Pierce’s suicidal intent scale score and serum serotonin level in suicidal group in different menstrual cycle phases

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Table 8 Correlation between serum serotonin and estrogen levels

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  Discussion Top


Suicide is a major health problem that accounts for ∼1 000 000 deaths/year, according to the WHO estimates in 2014 [4]. This self-injurious behavior proved to be more prevalent in women than men [44]. This draws the attention to study of the potential risk factors in female suicide attempts.

The relation between female suicide attempts and low estrogen levels can be attributed to the fact that oestrogen has a neuromodulatory role [20],[36],[45],[46]. Estrogen receptors are found in various brain areas including serotonergic neurons, which are known to play a role in depression and suicide [46],[47]. This suggests that the link between female suicidal behavior and female hormones is potentially through the modulatory effect of estrogen on serotonin [20].

Serotonin is now established as a neurotransmitter involved in the pathophysiology of many mood disorders. The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. The amino-acid tryptophan is the only precursor of serotonin. It is acted upon by tryptophan hydroxylase to form 5-hydroxytrypatophan which is then decarboxylated to serotonin. Then serotonin is degraded by monoamine oxidase-A enzyme to its main metabolite 5-hydroxyindoleacetic acid (5-HIAA). A large body of evidence documents the role of abnormalities in the serotonergic system in suicidal behavior. Different elements of this complex system, including serotonin receptors, serotonin transporter and tryptophan hydroxylase have been researched in this respect [22].

This work has been conducted to study the serum serotonin level as a potential risk factor in women suicide attempts, and the potential correlation between serum serotonin and serum estrogen levels in those women.

In this study, the suicide attempters had significantly lower serum serotonin levels than the women in the control group. This indicates an association between low serotonin levels and suicide attempts. This significance was found to be in the luteal and menstrual phases of the cycle. The suicidal intent was more pronounced among women committing suicide in the menstrual and late luteal phases (the low estrogen phases in the menstrual cycle) than in women in other phases of the cycle. Also, in the 23 women who attempted suicide in these two phases, a significant inverse correlation was found between their serum serotonin levels and their suicidal intents measured by PSIS scores.

In agreement with these findings, Rao et al. [48] and Spreux-Varoquaux et al. [49] reported significantly lower blood 5HT in suicide attempters compared with controls. Almeida-Montes et al. [50] reported significantly lower serum levels of 5HT in depressed patients who attempted suicide compared with those in depressed patients who never attempted suicide. Roggenbach et al. [51] and Mann et al. [52] reported lower levels of 5HT in platelets of suicide attempters compared with nonattempters or nonsuicidal patients.

Also a positive correlation was found between serum estrogen and serotonin levels. This correlation was statistically significant in all women (n=73) (r=0.358, P=0.002) and in the suicidal group (n=48) (r=0.314, P=0.03). In agreement with this finding, serotonin levels in the plasma are found to be higher in the follicular phase of cycling women than in postmenopausal women and estrogen replacement therapy in postmenopausal women caused a modest increase in plasma 5HT [53]. Estrogen treatment, orally or transdermally, increased urinary excretion of 5-HIAA, and this was interpreted as an enhancement of serotonin turnover. It follows that if estrogen increases plasma 5HT, this would lead to increased excretion of its metabolite 5-HIAA [54].


  Conclusion Top


In view of the data provided by this study, it can be concluded that an association between female suicide attempts and low serum serotonin levels may exist. The risk of suicide in women is proven to increase in women with low serum serotonin levels. Additionally, female suicide attempts in women with low serum serotonin levels tend to be more serious, with higher levels of suicidal intent. Also the age between 15 and 25 years, rural residency and unmarried state are risk factors in female suicide attempts.

Limitations of the study

The main limitation of this study was the small sample size that was limited by time and the wide range of exclusion criteria. So, large-scale studies are still recommended to stand on the exact relationship between serum serotonin levels and the risk for female suicide attempts.

Recommendations

This study recommends that:
  1. The serum serotonin level should be considered during the evaluation and follow-up of women with previous suicide attempts or at risk for suicide, especially in the late luteal and menstrual phases of the cycle (the low estrogen phases).
  2. Low serum serotonin level can be considered as an indicator of suicide attempts and high suicidal intent. Awareness of this association may help take any necessary actions to closely observe and monitor women at risk during these periods, in order to prevent recurrent attempts.
  3. Further large-scale studies are still needed to stand on the cut-off levels below which suicide risk is imminent.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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