Hormones (2022) 21:53–60

https://doi.org/10.1007/s42000-021-00320-3

ORIGINAL ARTICLE

Emotional intelligence scores in children and adolescents

with subclinical hypothyroidism—correlation with serum serotonin
and thyroid‑stimulating hormone (TSH) concentrations
George Κ. Arianas1 · Eirini Kostopoulou2 · Anastasios Ioannidis1 · Ioannis Dimopoulos3 · Christos Chiotis4 ·
Panagiotis Prezerakos1 · Bessie E. Spiliotis2 · Andrea Paola Rojas Gil1

Received: 22 April 2021 / Accepted: 3 September 2021 / Published online: 15 November 2021
© Hellenic Endocrine Society 2021

Abstract
Introduction Thyroxine is essential for nervous system development. Subclinical hypothyroidism (SCH), also known as
mild thyroid failure, is associated with impaired cognitive function in children and mood disorders in adults. Serotonin is
also involved in brain development as well as in mood and behavior modulation. The possible interaction between thyroid
function tests, serum serotonin concentrations, and emotional intelligence (EI) was studied.
Methods A total of 224 schoolchildren from the Peloponnese, Greece, aged 11–19, were included in the study, of whom
26.3% had SCH. Emotional quotients (EQ), such as well-being, self-control, emotionality, and sociability, were assessed
using the TEIQue-ASF questionnaire, and TSH, fT4, and serum serotonin concentrations were also evaluated.
Results Children and adolescents with SCH had a lower EQ total score (p < 0.001), EQ well-being score (p = 0.025), EQ
self-control score (p = 0.029), EQ emotionality score (p = 0.029), and EQ sociability score (p = 0.010) and lower serum
serotonin concentrations (p < 0.001).
Conclusions Children and adolescents with SCH exhibited lower EI scores and lower serum serotonin concentrations when
compared with age-matched healthy controls.

Keywords Subclinical hypothyroidism · Emotional intelligence · TSH · Serotonin

Introduction

Thyroxin is a major regulator of human brain development

and nervous system myelination [1]. Thyroid hormone
deficiency during the critical early stages of central nerv-
ous system development in the infant and child until 2 years
George Κ. Arianas and Eirini Kostopoulou contributed equally to of age, as occurs in congenital hypothyroidism, results in
this work.
mental retardation due to defective myelination and aber-
* Andrea Paola Rojas Gil ration of dendritic arborization [2]. Early identification and
arojas@uop.gr; apaola71@yahoo.com.mx treatment of congenital hypothyroidism is associated with
1
almost complete elimination of the risk of mental retarda-
Faculty of Health Sciences, Department of Nursing, tion. However, despite early treatment, intelligent quotients
Laboratory of Biology and Biochemistry, University
of Peloponnese, Dept. of Economics Building 2nd floor, Sehi (IQs) are significantly and persistently reduced in certain
area, Tripoli 22100, Greece children with congenital hypothyroidism, while general
2
Division of Pediatric Endocrinology, Department intelligence, language, memory, and attention/concentration
of Pediatrics, University of Patras School of Medicine, may also be impaired [3]. In addition, children with poorly
26504 Patras, Greece controlled hypothyroidism have been reported to be prone
3
School of Management, University of Peloponnese, to language, cognitive, social, and mental retardation com-
Kalamata, Greece pared with children with well-controlled hypothyroidism and
4
General Hospital of Kalamata, Kalamata, Greece children without thyroid dysfunction [4].

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54
Although overt hypothyroidism has been proven to be
a major contributor to neuropsychiatric dysfunction [5],
milder deficits have also been associated with subclinical
hypothyroidism (SCH). SCH is defined as elevated serum
TSH concentrations in the presence of circulating thyroid
hormones within the normal range [6]. The prevalence of
this disorder in children is estimated to be less than 10%,
ranging, according to two large population studies, between
1.7 and 2.9% [7], while in children who are overweight or
obese, the prevalence is higher, ranging from 7 to 23% [8].
The clinical features of SCH in childhood are in dispute,
with children presenting minimal or non-specific symptoms
[9]. Higher systolic and diastolic blood pressure have been
described in children and adolescents with SCH compared
with their euthyroid peers [10], as well as a positive corre-
lation between TSH concentrations and components of the
metabolic syndrome [11]. Increased frequency of migraine
headaches [12] and reduced growth velocity [13] have also
been reported. Thus far, limited data are available regard-
ing cognitive function, emotional status, and mood disor-
ders in children and adolescents with SCH. In a study by
Capalbo et al., neurocognitive function was not impaired in
persistent, mild, untreated SCH and was also not modified
by 2-year L-thyroxine supplementation [14].
Serotonin, a phylogenetically ancient neurotransmit-
ter, represents a key mediator of brain development, mood
modulation, and regulation of behavioral processes and
mental health [15]. Starting from the prenatal period, sero-
tonin acts as a growth factor, regulating cell division, dif-
ferentiation, and myelination in the brain [16]. It also sets
pathways needed for learning, thinking, and stress reactiv-
ity and regulates cognition, attention, emotion, pain, and
aggression [17]. Defects in its signaling are implicated in
increased risk for psychiatric disorders, such as schizophre-
nia and autism [18], and also in the development of anxiety
and depression, through its role in regulating the hypotha-
lamic–pituitary–adrenal axis, which is important for mental
health [19]. Low serum concentrations of serotonin have
been confirmed in adults with depression [20]. There is evi-
dence that serotonin can cross the blood–brain barrier uni-
directionally and bidirectionally in different locations of the
capillary cell membrane through the serotonin transporter
[21]. The majority of total serotonin (90%) is synthesized
in the human body by TPH1 in enterochromaffin cells in the
gut, where it is produced and from which it is distributed by
circulating platelets to various body sites [22]. Serotonin
is also expressed in other peripheral tissues and has been
shown to play different roles in the liver, in bone, in the
mammary gland, and in pancreatic β-cells [23].
Emotional intelligence (EI) is a commonly used psycho-
logical term referring to emotional competencies associated
with improved mental health [24], problem solving [25],
relationship quality [26], and academic and job performance
13
Hormones (2022) 21:53–60
[27], which all translate to coping effectively with environ-
mental demands and stressors. It is a measure of the abil-
ity to perceive, generate, regulate, and manage emotions in
order to guide thoughts and behavior [28]. As such, it plays a
significant role in determining success through social adap-
tation, teamwork, and effective management of stress and
reducing conflicts in professional and personal relationships
[29].
Data regarding the possible interaction between thyroid
function, serum serotonin concentrations, and emotional
competence in children and adolescents are currently lack-
ing. The objective of the present study was to examine the
possible relationship between SCH, peripheral serum sero-
tonin concentrations, and EI and to investigate the possible
correlation between serum TSH and peripheral serotonin
concentrations in Greek adolescents.
Materials and methods
Subjects
The current study is a cross-sectional study of 224 children
and adolescents from the Peloponnese, Greece, including
76 boys and 148 girls, aged 11–19 {median (min–max):
15.38 (11.0–19)}. The study population consisted of 196
participants randomly selected from a population of school
children from five schools in the Peloponnese (165 control
and 31 children with SCH), through multistage stratified
sampling. A total of 28 children with SCH from the out-
patient clinic of the Division of Pediatric Endocrinology
and Diabetes of the University General Hospital of Patras,
Greece, were selected.
Studies in children and adolescents have suggested
that the upper normal limit of TSH concentrations is
2.5–3.0 mU/L [30, 31]. We therefore defined the SCH group
as those who had TSH concentrations ≥ 3.5 mIU/L and nor-
mal free T4 concentrations and the control group as those
who had TSH concentrations below 3.5 mIU/L.
Height and weight were measured in all the participants,
and body mass index (BMI) and BMI percentile (BMI%) by
gender and age were calculated.
Exclusion criteria for participation in the study included
factors that could affect thyroid tests or peripheral serotonin
values, such as recent infection, recent surgery, medications,
depression, thyroid disease other than SCH, chronic kidney
disease, neoplasia, migraines, and celiac disease.
The study was approved by the Research Ethics Commit-
tee of the University of Peloponnese (18.03.2020). Informed
consent was obtained from the parents and/or guardians of
the participants after their being informed about the purpose
of the study. The anonymity of parents and children was
assured. The procedures followed were in accordance with
Hormones (2022) 21:53–60
the ethical standards of the Helsinki Declaration of 1975, as
revised in 1983.
Questionnaires
Several research tools were utilized in order to define and
measure EI [32]. One of the most widely used is TEIQue-
ASF, which is organized under four factors, as follows: well-
being, self-control, emotionality, and sociability. Fifteen of
the items express positive and 15 express negative facets.
A 7-point Likert-type scale is used for the evaluation (e.g.,
1 = strongly disagree and 7 = strongly agree). The total score
is derived by summing the score on each item after reverse
scoring for negative items. The higher the score, the higher
the EI of the subject [33].
All the children and adolescents were interviewed using
the standardized validated Greek translation of the Trait
EI Questionnaire-Adolescent Short Form (TEIQue-ASF)
questionnaire [34], a 30-item scale designed to measure
global trait EI through assessing different emotional quo-
tients (EQ). TEIQue-ASF is based on the long form of the
TEIQue. The recommended age range for use of the ques-
tionnaire is 13–17 years; however, the questionnaire has
been used successfully in children as young as 11 years old
[35]. Based on the above, children and adolescents aged
11–19 years old were included in the current study. Demo-
graphic data and a thorough medical history, including
comorbidities, were also obtained from the parents of the
participants.
Blood samples, laboratory measurements,
and serum assays
Peripheral blood samples were collected from all par-
ticipants in the fasting state, between 8 and 9 am. Thyroid
function tests including TSH and free thyroxine (fT4) as
well as serum serotonin were measured. TSH and fT4 were
measured by immunoassay (Electrochemiluminescence
Immunoassay, Roche Diagnostics, Switzerland). Peripheral
serum serotonin was measured by ELISA using the serotonin
enzyme-linked immunosorbent assay (ELISA) kit (Abnova
Heidelberg, Germany). The intra- and inter-assay CVs are
11.03 and 11.25%, respectively.
Statistical data analysis
Data for continuous variables are presented as median val-
ues (min and max). The Mann–Whitney and Kruskal–Wallis
tests were used to compare values between two or more than
two groups, respectively. Spearman’s correlation was used to
evaluate the relation between quantitative variables.
55
In order to examine the effect of SCH and TSH levels on
EI regardless of the effect of gender and age, we fitted linear
regression models with and without SCH [36].
The statistical analysis was performed using the IBM
Corp. Released 2013. IBM SPSS Statistics for Windows,
Version 22.0. Armonk, NY: IBM Corp, and the significance
level was set at 5%.
Results
The children’s and adolescents’ characteristics, including
age, gender, BMI%, EQs, thyroid function tests, and serum
serotonin levels are presented in Table 1.
TSH and EI
Adolescents with SCH had a lower EQ total score
(p < 0.001), EQ well-being score (p = 0.025), EQ self-control
score (p = 0.029), EQ emotionality score (p = 0.029), and EQ
sociability score (p = 0.001) (Table 1).
TSH and EI by age and gender
Two-step linear regression analysis showed a statistically
significant effect of TSH on the total EI score and on the
emotional score, as is detailed below.
Effect on total EI score
In the first step of the two-step linear regression analy-
sis, age and gender were not shown to have a statistically
significant effect on the emotional score (R2 = 0.003, F
(2221) = 0.379, p = 0.685). In the second step, SCH was
entered into the equation with a statistically significant
effect (R2 = 0.062, F (3,220) = 4.868, p = 0.003). SCH
was negatively related to the total score (β =  − 0.325,
SE = 0.087, t =  − 3,715, p < 0.001) and explained 5.9% of
its variability.
Effect on emotional score
In the first step of the two-step linear regression analysis, age
and gender were not shown to have a statistically significant
effect on the emotional score (R2 = 0.012, F (2221) = 1.410,
p = 0.246). In the second step, SCH was entered into the
equation with a statistically significant effect (R2 = 0.035,
F (3220) = 2.672, p = 0.048). The presence of SCH was
negatively related to the emotional score (β =  − 0.272,
SE = 0.120, t =  − 2,268, p = 0.024) and explained 2.3% of
its variability.
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56 Hormones (2022) 21:53–60

Table 1  Median values of the baseline characteristics in all studied categories

Characteristics Total population Subclinical hypothyroid- Control p value
N = 224 ism (SCH) N = 165 (SCH vs. control)
N = 59

Age 15.50 15.00 16.00 0.499

(11.0–19.00) (11.00–19.00) (11.00–19.00)
Gender 76 males 20 males 56 males 0.995
148 females 39 females 109 females
BMI % 69.25 73.90 68.10 0.175
(12.60–99.50) (26.50–99.50) (12.60–98.80)
EQ total score 4.94 4.60 5.00 < 0.001
(3.60–6.60) (3.60–5.90) (3.70–6.60)
EQ well-being score 5.70 5.20 5.70 0.025
(2.50–7.00) (2.50–7.00) (2.50–7.00)
EQ self-control score 4.50 4.20 4.50 0.029
(2.00–6.30) (2.00–6.30) (2.00–6.30)
EQ emotionality score 4.90 4.80 5.00 0.029
(3.10–6.80) (3.10–6.60) (3.0–6.80)
EQ sociability score 4.90 4.70 5.00 0.010
(2.70–6.80) (2.70–6.50) (2.70–6.80)
TSH concentrations 2.06 4.11 1.77 < 0.001
(mIU/L) (0.38–6.27) (3.54–6.27) (0.38–3.47)
fT4 concentrations 0.95 0.93 0.96 0.008
(ng/dL) (0.80–1.95) (0.81–1.25) (0.80–1.95)
Serum serotonin concentrations 117.90 103.50 122.30 < 0.001
(ng/mL) (79.00–166.80) (79.00–165.70) (92.80–166.80)

Values are presented as median (minimum–maximum). EQ emotional quotient, BMI% body mass index percentile, TSH thyroid-stimulating hor-
mone, fT4 free thyroxine. Νormal EQ scores: 1–7, normal BMI%: 10–85%, normal serum serotonin concentrations: 101–283 ng/ml. The Mann–
Whitney test was used to calculate the differences between subclinical hypothyroidism and control samples

TSH and serotonin concentrations
Children and adolescents with SCH had lower serum ser-
otonin concentrations (p < 0.001) (Table 1). A negative
correlation was found between TSH and serotonin levels
{R =  − 0,439, (p < 0.001)}.
There was no statistically significant difference in the
level of serotonin between children with neonatal jaundice
and those without (p = 0.775).
No correlations were found between obesity (BMI%) or
gender and the studied parameters.

Comorbidities in relation to SCH and EI
No statistically significant correlation was found between
the children’s comorbidities and EI, with the exception of
neonatal jaundice. Neonatal jaundice was found to have a
statistically significant effect on the self-control score only
among children with SCH (N = 59) (p = 0.020). Children
with SCH and neonatal jaundice showed a lower score
(median = 3.6) compared with children with SCH but with-
out neonatal jaundice (median = 4.5). In children without
SCH, neonatal jaundice did not show a statistically sig-
nificant effect on the self-control score (p = 0.358, score of
children without jaundice median = 4.7, score of children
with jaundice median = 4.5).
Discussion
The main findings of the present study suggest that children
and adolescents aged 11 to 19 with SCH exhibit impaired
EI and lower peripheral serotonin concentrations when
compared with age-matched healthy controls. Further-
more, of particular interest were our findings of a negative
correlation between serum TSH and peripheral serotonin
concentrations.
The establishment of the upper normal limit of TSH
concentrations in children still poses a challenge. Several
studies have reported that the median TSH concentration
in healthy individuals varies between 1.4 and 1.8 mU/L in
adults and peaks at approximately 1.5 in children and ado-
lescents, although an upper normal limit of 2.5 − 3.0 mU/L
has been suggested as being more realistic [30, 31]. In

13
Hormones (2022) 21:53–60
addition, a reference TSH range between 0.4 and 3.77
mIU/L (2.5 th and 97.5 th percentile) for healthy adult
individuals has been reported by Kratzsch et al. [37] and
between 0.25 and 2.12 mIU/L by Völzke et al. [38].
The actions of thyroid hormones in the brain are extremely
complex and seem to affect evolving emotional and cognitive
development. The association between overt hypothyroidism
and mood disorders, such as major depression and melancho-
lia, is well documented in adults [39]; however, data on mood
disorders in adult patients with SCH, such as depression and
anxiety, are still controversial. Large population studies have
reported a higher frequency of depression and anxiety [40],
whereas other studies found no differences in mood disor-
ders in adults with SCH compared with euthyroid subjects
[41]. A 2018 meta-analysis indicated that SCH is associated
with depression in adults younger than 60 years old [42].
On the other hand, EI has not been studied in children and
adolescents with SCH. Our study is the first to evaluate the
association between the two and to assess all the parameters
of EI in children and adolescents with SCH.
In addition, the present study showed a correlation of
neonatal jaundice with the self-control score only among
children with SCH. Large studies on the long-term conse-
quences of neonatal hyperbilirubinemia have shown that
neonatal jaundice is correlated with cognitive complaints,
lower levels of subjective well-being, and a tendency to poor
adjustment in adult life [43]. On the other hand, it is known
that transient neonatal hypothyroidism may present with
indirect or direct hyperbilirubinemia [44]. However, there
was no report of neonatal or congenital hypothyroidism in
the participants of the present study.
Furthermore, the serotonergic system is implicated in
mood, emotion, and control of behavioral functions, as well
as in a variety of psychiatric disorders, most prominently anxi-
ety and depression [45]. Accumulated evidence suggests that
serotonin has also been incriminated in major depressive dis-
order, one of the most debilitating mental health diseases. Pro-
posed mechanisms include dysfunction of the serotonin (5-HT)
receptors and of the neuronal plasma membrane transporter
protein (SERT), which is one of the main targets of antidepres-
sant therapy [46]. A reduction of serotonin levels is associated
with an increased risk of being affected by depression [47].
Although a sizeable body of literature documents the separate
role of serotonin in mood disorders [48], studies regarding the
direct role of serotonin in emotional processing are scarce. It
has been reported that peripheral blood serotonin is an acces-
sible measure of the availability of circulating 5-HT and may
serve as a peripheral proxy for central 5-HT serotonin [49, 50].
With regard to EI, which is a risk factor for mood distur-
bance, elevated serotonin levels have been associated with worse
performance [51]. In contrast, emerging evidence suggests an
interaction between serotonin and brain-derived neurotrophic
factor (BDNF), another neurotransmitter implicated in mood
57
regulation, in healthy men, which is associated with superior
emotional understanding, one domain of EI. Specifically, dis-
cordant levels of the two neurotransmitters, i.e., high peripheral
serotonin levels in conjunction with low BDNF levels, demon-
strated superior ability to understand complex emotional mean-
ings, emotional transitions, and emotional situations [52].
Additionally, decreases in peripheral measures of sero-
tonin in peripheral whole blood, plasma, and platelets have
been described in mood and other neuropsychiatric disor-
ders in older adults [53]. Moreover, low levels of peripheral
serotonin have been related to mood disorders in children
and adolescents [54]. Another study presented a descriptive
approach to the association of peripheral serotonin with emo-
tional brain functions in children and adolescents specifically,
with a broad measure of overt behavioral problems such as
impulsive aggression and behavioral disinhibition [55].
Our study is the first to investigate the correlation between
serum TSH and serotonin concentrations in children and
adolescents, demonstrating a negative correlation between
the two. The interaction of neurotransmitter systems such
as serotonin and the hypothalamic-pituitary-thyroid axis
has been suggested as a possible underlying mechanism of
action in individuals with mood disorders [56]. Existing
evidence from neuroendocrine challenge studies in humans
suggests that hypothyroidism is associated with diminished
serotonin responsiveness, which is restored after thyroid
replacement therapy [57]. It has also been hypothesized that
in adult patients with depression, blunted TSH response to
the TRH stimulation test might be a compensatory mecha-
nism for diminished central serotonin activity [58]. Animal
studies have additionally shown that thyroid status signifi-
cantly affects serotoninergic neurotransmission in the adult
brain and that increased thyroid hormone concentrations
elevate serotonin neurotransmission [59].
There are restrictions on human research in this field;
however, considering the well-established role of serotonin
in the pathogenesis of depression, it can be speculated that
the serotonin system may be involved in the mood-modulat-
ing effects of thyroid hormones in patients with mood dis-
orders. This may also explain the increased effectiveness of
administration of combined treatment with antidepressants
that affect the serotonin system and thyroid hormones in
patients with affective disorders, whereas thyroid hormones
alone have limited clinical effects [60].
In conclusion, to the best of our knowledge, no other
studies exist evaluating EI quotients and serum serotonin
concentrations in children and adolescents with SCH. One of
the most interesting findings of our study is the relationship
between SCH and EI and, specifically, the finding that EI
seems to be negatively affected in children and adolescents
with this disorder.
The current study has certain limitations, including the
fact that the pubertal status and environmental factors, such
13
58
as nutrition and the socioeconomic status of the participants,
were not documented. Another limitation of the study is
that the kit used for serotonin measurement is not validated
against a gold standard (e.g. mass spectrometry). In addi-
tion, the intra- and inter-assay CVs of serotonin are high.
Furthermore, other potential sources of circulating serotonin
may have affected the results of this study.
Additional studies taking into consideration parameters
that were not investigated in the present study are required
in order to investigate as well as, possibly, to confirm the
present findings. Moreover, further clarification of the role
of thyroid hormones and serotonin in the developing brain
is needed in order to elucidate the effect of possible cross-
talk between the hypothalamic-pituitary-thyroid axis and the
serotonin pathway on EI, cognitive ability, and other poten-
tial brain functions in children and adolescents.
Acknowledgements We would like to thank all the respondents who
dedicated their time to participate in this survey.
Authors’ contributions George Κ Arianas Eirini Kostopoulou, Bessie
E. Spiliotis, and Andrea Paola Rojas contributed to the conception,
design, and completion of the study, as well as the preparation of the
final manuscript considered for publication. Christos Chiotis Anasta-
sios Ioannidis and Panagiotis Prezerakos contributed to the acquisition,
analysis, and interpretation of data. Ioannis Dimopoulos performed
the statistical analysis. Andrea Paola Rojas confirms that she had full
access to all the data in the study and takes responsibility for the integ-
rity of the data and the accuracy of the data analysis. All the authors
contributed to either the drafting of the manuscript or its critical revi-
sion. They also gave final approval of this version to be published and
agree to be accountable for all aspects of the work in ensuring that
questions related to the accuracy or integrity of any part of the work
are appropriately investigated and resolved.
Data availability statement The data that support the findings of this
study are available from the corresponding author upon reasonable
request.
Declarations
Ethical approval The study was in accordance to the Declaration of
Helsinki (1964) and was approved by the Ethics Committee of the
Department of Nursing, University of Peloponnese, Greece. No animal
studies were carried out by the authors for this article.
Conflict of interest George Κ Arianas, Eirini Kostopoulou, Anastasios
Ioannidis, Ioannis Dimopoulos, Christos Chiotis, Panagiotis Prezera-
kos, Bessie E. Spiliotis, and Andrea Paola Rojas Gil have no conflict
of interest to disclose.
Informed consent The current research involved the participation
of human subjects. To partake in the study, individuals gave their
informed consent in a written format, while participation was voluntary
and anonymity was assured.
13
Hormones (2022) 21:53–60
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