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1 23
 Author's personal copy
Eat Weight Disord
DOI 10.1007/s40519-013-0056-5
ORIGINAL ARTICLE
Psychopathological traits of adolescents with functional
hypothalamic amenorrhea: a comparison with anorexia nervosa
Monica Bomba • Fabiola Corbetta • Luisa Bonini
Alessandro Gambera • Lucio Tremolizzo •
Francesca Neri • Renata Nacinovich
Received: 24 April 2013 / Accepted: 23 July 2013
! Springer International Publishing Switzerland 2013
Abstract
Background Functional hypothalamic amenorrhea (FHA)
is a form of anovulation, due to the suppression of hypo-
thalamic–pituitary–ovarian axis, not related to identifiable
organic causes. Like adolescents with anorexia nervosa
(AN), subjects with FHA show dysfunctional attitudes, low
self-esteem, depressive mood, anxiety and inability to cope
with daily stress. The aim of the study is to examine
similarities and differences between FHA and AN in terms
of clinical profiles and psychological variables.
Methods 21 adolescents with FHA, 21 adolescents with
anorexia nervosa, and 21 healthy adolescents were inclu-
ded in the study. All the teenagers completed a battery of
self-administered psychological tests for the detection of
behaviors and symptoms attributable to the presence of an
eating disorder (EDI-2), depression (CDI), and alexithymia
(TAS-20).
Results Different from healthy controls, subjects with
FHA and with AN shared common psychopathological
M. Bomba (&) ! F. Corbetta ! F. Neri ! R. Nacinovich
Clinic of Child and Adolescent Mental Health, Ospedale San
Gerardo di Monza, University of Milan Bicocca, Via Pergolesi,
33, 20900 Monza (MB), Italy
e-mail: monica.bomba@gmail.com
L. Bonini
Department of Childhood and Adolescent Neuropsychiatry,
Spedali Civili, Piazzale Spedali Civili 1, 25123 Brescia, Italy
A. Gambera
Department of Gynecological Endocrinology, Spedali Civili,
Piazzale Spedali Civili 1, 25123 Brescia, Italy
L. Tremolizzo
Department of Neurology, University of Milan Bicocca,
via Pergolesi 33, 20900 Monza, Italy
•
aspects, such as maturity issues, social insecurity and
introversion, a tendency to depression, excessive concerns
with dieting, and fear of gaining weight. Nevertheless,
adolescents with AN presented a more profound psycho-
pathological disorder as observed at test comparisons with
subjects with FHA.
Conclusions Results show a clinical spectrum that
includes AN and FHA and suggest the necessity to treat
FHA with a multidisciplinary approach for both organic
and psychological aspects.
Keywords Functional hypothalamic amenorrhea !
Anorexia nervosa ! Adolescence ! Psychopathology !
Multidisciplinary approach
Introduction
Functional hypothalamic amenorrhea (FHA) is a common
and theoretically reversible form of anovulation, due to the
suppression of hypothalamic–pituitary–ovarian axis, not
related to identifiable organic causes. The disorder is
characterized by amenorrhea of 6-month duration, in pre-
viously normal cycling fertile women [1]. Hypothalamic
causes are the most common type of amenorrhea in ado-
lescents [2] and FHA accounts for an estimated 15–48 % of
cases of secondary amenorrhea [3]. This condition is
determined by the disruption of GnRH drive and reduction
in gonadotropins pulsatile secretion [4]. Since Reifenstein
[5] defined FHA as a syndrome in which ‘‘overt or latent
psychological disturbance’’ disrupts menstrual functioning,
the basic hypothesis for the etiology of amenorrhea was
that metabolic challenge and psychogenic stress interact to
influence reproductive performances by acting on the
hypothalamus [6, 7]. Numerous factors have been
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 Author's personal copy
implicated: low body weight and weight loss, high intensity
exercise training and a large amount of environmental and
personal stressors have been recognized as specific triggers
for the onset of the disorder [1, 4, 8–10]. The decrease in
energy balance, with a concomitant reduction of leptin and
elevation of ghrelin, appears to play an important role in
both weight loss- and exercise-induced forms of FHA [11–
13]. It has also been demonstrated that stress can desyn-
chronize the GnRH neuronal network through the over
activity of hypothalamus–pituitary–adrenal axis, with the
consequent increase in secretion of corticotrophin-releasing
hormone (CRH), ACTH, cortisol and endogenous opioids
[14–16]. Other physiological changes involved in FHA
include disturbance of the hypothalamic–pituitary–thyroid
axis, increase in dopaminergic tone, amplification of noc-
turnal melatonin rhythm and reduction of IGF-1 activity [1,
17–19]. Russell [20] hypothesized that stressful stimuli in
psychogenic amenorrhea could include extreme danger and
privations (wars, starvation, etc.), deep familiar deprivation
(death of parent, etc.), minor life changes (beginning
school, fear of pregnancy, etc.) and severe psychiatric
disorders. Psychological assessments in women with FHA
show dysfunctional attitudes (perfectionist performance
standards, concern about the judgments of the others, need
for social approval), low self-esteem, depressive mood,
anxiety and inability to cope with daily stress [3, 4, 11, 21].
All these features are similar to those of individuals pre-
senting with eating disorders such as bulimia and anorexia
nervosa. It is well known that the onset of anorexia nervosa
(AN), a psychiatric disorder characterized by weight loss,
intense fear of gaining weight or becoming fat and dis-
turbed body image [22], typically occurs during adoles-
cence. The prevalence of the disease among adolescents is
between 0.5 and 1 % and the incidence is 5–10/100,000 of
new cases per year between 15 and 18 years of age [23]. A
number of endocrine and metabolic disturbances have been
described in patients with AN including alteration in the
hypothalamic–pituitary–ovarian axis, delayed puberty,
hypercortisolism, hypothyroidism and IGF-1 deficiency,
among others [24]. Hypothalamic amenorrhea, which is a
debatable diagnostic criterion in AN [22], may persist after
re-feeding and weight restoration [25]. Among high-school
students [26], adolescents who reported vomiting to control
their weight one to three times per month were 60 % more
likely to have irregular menses than those who did not
vomit. Menstrual dysfunction may, therefore, be viewed as
a clinical marker or ‘‘warning sign’’ for disordered eating
behaviors, and thus it is an important tool for the assess-
ment of the overall health status of adolescent girls [27].
Accordingly, the Workgroup for Classification of Eating
Disorders in Children and Adolescents affirmed that dif-
ferent diagnostic thresholds and categories are necessary
to describe eating disorders in the younger population [28].
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In line with these assumptions, some changes have been
introduced in the new DSM-V to diagnose eating disorders.
For instance, a new category, the ‘‘avoidant/restrictive food
intake disorder’’ (ARFID), has been included to describe
children and adolescents with a persistent and significantly
distorted food intake (range and quantity). Furthermore, the
category ‘‘elimination disorders’’ (ED), previously inclu-
ded under disorders first diagnosed in infancy/childhood/
adolescence, exists now as an independent classification in
DSM-V. Changes in the criteria for the ‘‘binge-eating
disorder’’ (BED) have been made: the minimum average
frequency of binge eating required for diagnosis has been
changed from at least twice weekly for 6 months to at least
once weekly over the last 3 months (as well as in bulimia
nervosa) [29]. Nevertheless, none of these new DSM-V
formulations satisfactorily describe subjects with FHA.
In literature, it is reported that adult women with FHA
have an altered attitude toward eating and a higher inci-
dence of subclinical eating disorders, especially of bulimic
type [30–32]. On the contrary, there are few clinical studies
that address eating disorders, in particular subthreshold AN
of the restrictive type, and FHA during adolescence [33].
These differences of clinical expression of FHA in ado-
lescence and in adulthood might be explained by the dif-
ferent age of occurrence of AN (peak at 15–18 years),
more precocious than that of other eating disorders. In fact,
peak period of risk for onset is between 17 and 20 for BN
[34] and BED, and between 18 and 20 for purging disorder
[35]. Moreover, subthreshold BN shows a ten times higher
lifetime prevalence (6.1 %) when compared to that of AN
(0.6 %) [35]. Adolescence represents a complex period in
which subjects should integrate bodily changes and sexual
development in their self-image. Moreover, the nature–
nurture interplay, consisting also of the biological and
psychological transformation occurring during this partic-
ular period of life, represents the basis of the final pheno-
typic expression of the disease [36], as pre-condition of the
response to stress in the subjects who develop FHA [33].
The aim of the present study is to evaluate psycho-
pathologic traits of adolescents with FHA and AN, and to
examine similarities and differences between these two
conditions in terms of clinical profile and psychological
variables. To our knowledge, no other studies have focused
on this matter before.
Materials and methods
Twenty-one adolescents admitted to the Day Hospital of
Gynecological Endocrinology for a persistent amenorrhea,
then diagnosed as having FHA, were enrolled. All the
subjects underwent a complete anamnesis to identify the
possible causes of FHA (including information about
 Author's personal copy
Eat Weight Disord
physical exercise), a clinical examination and the calcula-
tion of body mass index (BMI), blood routine and hormone
assays and a radiological evaluation of the sella turcica.
Furthermore, subjects underwent a psychiatric evaluation
with a specialist in neuropsychiatry, expert in adolescent
disorders. FHA was then diagnosed by clinical (amenor-
rhea for a period C6 months) and hormonal findings (low
or normal levels of gonadotropins and estradiol), and the
negativity of the radiological evaluation of the sella turcica.
Hormonal assays were assessed in fasting conditions
between 8:00 and 9:00 a.m. in duplicate. Based on the
hormonal profile and history, no FHA patient had poly-
cystic ovary syndrome, Cushing or Addison disease,
premature ovarian failure, hyperprolactinemia, hypo/
hyperthyroidism, drug abuse, or had used any medication
in the 6 months preceding admission. Anorexia and buli-
mia nervosa, BEDs and EDNOS were excluded in these
subjects, since none responded to the criteria defined by the
Diagnostic and Statistical Manual of Mental Disorders
(DSM-IV-TR) [22].
Since our previous study [33] demonstrated that adoles-
cents with FHA present clinical features similar to those of
the subjects with restrictive AN, we enrolled a group of 21
age-matched (±1 year) adolescent girls with AN of the
restrictive type to make a comparison. The adolescents were
all recruited after their first admission to the Day Hospital for
Eating Disorders. The diagnosis of AN was made by a spe-
cialist in neuropsychiatry, expert in adolescent disorders,
according to the DSM-IV criteria. Blood assessments were
performed, the BMI calculated and the physical exercise was
evaluated. An exclusion criterion for the recruitment of FHA
and AN groups was the presence of a co-morbidity with a
neurological disease or a personality disorder.
Finally, the control group was made up of 21 schoolgirls
(community volunteers), matched for age (±1 year), with
normal BMI and regular ovulatory menstrual cycles. All
healthy controls had no history of thyroid diseases, showed
absence of androgenic symptoms and they had not taken
steroid hormones in the last 12 months. Blood determina-
tions were not performed on the controls.
All the subjects’ and parents’ informed consents were
obtained to join the study.
The socio-economic status of the subjects was deter-
mined using the Hollingshead Index of Social Position
(ISP) (Hollingshead A., The four-factor index of social
status. Unpublished manuscript, Yale University, Depart-
ment of Sociology, New Haven, CT; 1975).
All the teenagers included in the study filled in the
following self-administered tests:
1. Children’s Depression Inventory (CDI) [37]: a ques-
tionnaire for the assessment of depressive traits used
for children and adolescents. The questionnaire
consists of 27 items, with 3 multiple choices of
response. Total score is from 0 to 54. The authors
report a cut-off of 19, over which the subject is
considered characterized by depressive traits. The
scores of 17 and 18 identify subjects at risk.
2. Eating Disorder Inventory-2 (EDI-2) [38]: a question-
naire to evaluate eating attitudes and symptoms usually
associated with eating disorders. The scale consists of
91 items, each with 6 multiple choices; score assign-
ment goes from 0 (the least ‘pathological’ response) to
3 (the most ‘pathological’ response). Items are divided
into 11 main subscales: drive for thinness (DT),
bulimia (BU), body dissatisfaction (BD), ineffective-
ness (IN), perfectionism (P), interpersonal distrust
(ID), interoceptive awareness (IA), maturity fears
(MF), asceticism (ASC), impulse regulation (IR),
social insecurity (SI).
3. Toronto Alexithymia Scale-20 (TAS-20) [39, 40]: a
questionnaire to evaluate the presence of alexithymia.
The test is based on 20 items and a 5-point Likert scale
for answers. TAS-20 has 3 factors including: difficulty
in identifying feelings and distinguishing them from
bodily sensations (F1), difficulty in describing feelings
to others (F2), and externally oriented thinking (F3).
The presence of alexithymia is defined when the score
is over 61; scores from 51 to 60 are considered as
‘‘borderline’’ (at risk).
Statistical analysis
All values were expressed as mean and SD. One-way
ANOVA and Bonferroni post hoc test for multiple com-
parisons were performed to compare socio-demographic
and clinical continuous variables. Since the low BMI is a
clinical criterion for the diagnosis of AN, firstly Spear-
man’s non-parametric test was performed to study possible
correlations between BMI and the test variables. As a
second step, since many of the test variables were inversely
correlated with BMI, an ANCOVA test and Bonferroni
post hoc test for multiple comparisons were performed to
compare test scores carried out in the three groups,
including the BMI in the model as a covariate to control its
influence on the dependent variables (test scores). To
address our hypothesis of the spectrum, we have also
performed a post-test analysis of trends whenever a sig-
nificant difference between the variables in the three
groups was observed at the ANCOVA analysis.
Pearson Chi-square test was performed to compare cate-
gorical variables data (expressed as absolute numbers and
percentages, %). A P value\0.05 was considered statistically
significant. The statistical package SPSS 19.0 (SPSS Inc.
Corp., USA) was used to carry out the statistical analysis.
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Table 1 Socio-demographic and clinical features of subjects in the three groups

Anorexia Nervosa Functional Hypothalamic Healthy controls ANOVA
(n = 21) Amenorrhea (n = 21) (n = 21) p

Age (years) 15.9 (1.1) 16.2 (0.9) 16.2 (1.1) n.s.

Intense physical exercise*, C3 times/week 8 (38.1 %) 11 (52.4 %) 7 (33.3 %) n.s.
SES-Hollingshead Index 30.8 (16.7) 34.2 (18.6) 32.0 (12.0) n.s.
BMI (kg/m2) 15.5 (1.8)a, c
18.4 (1.1)b 19.7 (1.8) 0.000
LH (mIU/mL) 1.37 (1.4) 2.30 (1.4) N/P 0.037
FSH (mIU/mL) 3.2 (2.6) 4.83 (0.56) N/P 0.021
The Pearson Chi-square test was performed to compare categorical variables (*), meanwhile the analysis of variance (ANOVA) followed by
Bonferroni post hoc test was used for assessing differences among the continuous variables carried out in the three groups
Values are expressed as: mean (SD) and as absolute values and percentages (*)
SES socio-economic status according to Hollingshead’s 4-factors index, BMI body mass index, n.s. not significant, N/P not performed
a b c
p \ 0.001 vs controls, p \ 0.05 vs controls, p \ 0.001 vs FHA (Bonferroni post hoc analysis)

Table 2 Correlations between BMI and test variables the healthy controls. As expected, subjects with AN pre-
Correlations with BMI
sented significantly higher scores at all the subscales
(except for ‘‘bulimia’’ and ‘‘impulse regulation’’), when
Spearman, R p compared to controls. Table 4 shows mean scores at the
Drive for thinness -.365 0.003 CDI and at the TAS-20 carried out in the three groups. At
Bulimia 0.108 n.s. CDI, the subjects with AN presented significantly higher
Body dissatisfaction -.053 n.s. scores when compared to the subjects with FHA (?63 %)
Ineffectiveness -.425 0.001 and to the healthy controls, while subjects with FHA
Perfectionism -.263 0.037 showed higher scores than controls. According to CDI, 13
Interpersonal distrust -.396 0.001 (61.9 %) adolescents with AN and 2 (9.5 %) adolescents
Interoceptive awareness -.412 0.001 with FHA presented depressive traits (CDI total score C19)
Maturity fears -.329 0.009
(see Fig. 1).
Asceticism -.187 n.s.
Both groups of adolescents with AN and adolescents
Impulse regulation -.202 n.s.
with FHA were characterized by higher scores at the
alexithymia scale, according to the overall TAS-20 total
Social insecurity -.319 0.011
score (?46 and ?32 %), and to the ‘‘difficulties in
CDI total score -.464 0.000
describing feelings’’ subscale (?70 and ?62 %), when
TAS-20 total score -.487 0.000
compared to the healthy subjects. At the subscale ‘‘diffi-
Spearman non-parametric test was performed to consider possible culty in identifying feelings’’, adolescents with AN
correlations between BMI and the test variables
obtained significantly higher scores, when compared to the
n.s. not significant
subjects with FHA and to the healthy controls.
Moreover, according to TAS-20, 15 (71.4 %) adoles-
Results cents with AN and 12 (57.1 %) adolescents with FHA
versus 4 (19 %) healthy controls showed alexithymic traits
Clinical and socio-demographic features of all the recruited (TAS-20 total score C61; see Fig. 2). For all the variables
subjects are shown in Table 1. As expected, most of the analyzed, the post-test analysis showed the presence of a
test variables collected were inversely correlated with BMI linear trend between AN, FHA and controls.
(see Table 2).
At the EDI-2 (see Table 3), adolescents with AN
showed scores two- to threefold higher than those of ado- Discussion
lescents with FHA at the ‘‘drive for thinness’’, ‘‘ineffec-
tiveness’’, ‘‘interpersonal distrust’’ and ‘‘interoceptive The aim of the present study was to examine similarities
awareness’’ subscales. On the other hand, subjects with and differences in a group of adolescents with FHA,
FHA showed fivefold higher scores at the subscale ‘‘drive compared to age-matched females with AN. These two
for thinness’’, and twofold higher at the ‘‘maturity fears’’ conditions presented some similar clinical aspects, together
and at the ‘‘social insecurity’’ subscales, when compared to with an overall difference with regard to the severity of

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Table 3 EDI-2 profile (mean scores and SD) in the three groups
Anorexia nervosa Functional hypothalamic Healthy controls ANCOVA Post-test for linear trend
(n = 21) amenorrhea (n = 21) (n = 21) p
R2 value p

Drive for thinness 12.1 (7.4)a, d

6.7 (6.3)b 1.1 (1.7) 0.000 0.394 0.000
Bulimia 1.0 (1.4) 1.4 (2.0) 0.8 (1.3) n.s. N/P N/P
Body dissatisfaction 11.0 (7.2)b 8.8 (7.3) 5.7 (4.9) 0.011 0.102 0.011
a, d
Ineffectiveness 7.9 (7.2) 3.7 (5.6) 1.0 (1.4) 0.005 0.226 0.000
Perfectionism 4.8 (3.6)b 3.6 (3.4) 2.1 (2.0) 0.023 0.118 0.006
Interpersonal distrust 6.5 (3.7)a, d
3.6 (2.9)d 1.2 (1.4) 0.000 0.379 0.000
Interoceptive awareness 9.4 (7.0)a, c
3.3 (3.7) 1.7 (2.6) 0.000 0.299 0.000
Maturity fears 6.1 (3.2)b 5.2 (3.3)b 1.7 (1.9) 0.001 0.281 0.000
Asceticism 6.6 (4.7)a 5.0 (2.9) 3.0 (3.1) 0.001 0.144 0.002
Impulse regulation 5.1 (4.8) 2.7 (4.2) 2.1 (2.9) n.s. N/P N/P
Social insecurity 6.2 (4.0)b 4.8 (4.4)b 1.5 (2.3) 0.003 0.219 0.000
Analysis of covariance (ANCOVA) followed by Bonferroni post hoc test was used for assessing differences among the three groups, controlling
for the BMI as a possible confounding factor (covariate)
Values are expressed as: mean (SD)
Post-test for linear trend was performed to verify whether the column means increase (or decrease) systematically as the columns go from left to
right
n.s. not significant, N/P not performed
a b c d
p \ 0.001 vs controls, p \ 0.05 vs controls, p \ 0.001 vs FHA, p \ 0.05 vs FHA (Bonferroni post hoc analysis)

Table 4 CDI and TAS-20 profiles (mean scores and SD) in the three groups
Anorexia nervosa Functional hypothalamic Healthy controls Ancova Post-test for
(n = 21) amenorrhea (n = 21) (n = 21) p linear trend
R2 value p
b b
CDI total score 18.4 (8.0) 11.3 (6.2) 5.1 (3.3) 0.002 0.450 0.000
a a
TAS-20 total score 59.2 (10.2) 53.5 (10.6) 40.6 (9.6) 0.000 0.363 0.000
TAS-20 subscales:
F1. Difficulty Describing Feelings 20.4 (7.9)a 19.4 (6.5)b 12.0 (3.9) 0.001 N/P N/P
a, c
F2. Difficulty Identifying Feelings 18.8 (4.4) 14.8 (4.1) 11.7 (4.6) 0.001 N/P N/P
F3. Externally Oriented Thinking 20.5 (5.1) 19.3 (4.8) 16.9 (4.7) n.s. N/P N/P
Analysis of covariance (ANCOVA) followed by Bonferroni post hoc test was used for assessing differences among the three groups, controlling
for the BMI as a possible confounding factor (covariate)
Post-test for linear trend was performed to verify whether the column means increase (or decrease) systematically as the columns go from left to
right
Values are expressed as: mean (SD)
n.s. not significant, N/P not performed
a b c
p \ 0.001 vs controls, p \ 0.05 vs controls, p \ 0.05 vs FHA (Bonferroni post hoc analysis)

clinical profiles and of psychological patterns. In agree-
ment with our previous study [33], adolescent subjects with
FHA showed subthreshold eating disorders characterized
by concerns about body image, dieting and fear of gaining
weight (as described in the ‘‘drive for thinness’’ EDI-2
subscale). Nevertheless, their scores were much lower than
those of patients with AN.
Moreover, the subthreshold disordered eating of ado-
lescents with FHA was prevalently of a ‘‘restrictive type’’.
These data were in contrast with reports of prevalent
bulimic symptoms in adult women with FHA [12]. In fact,
restrictive traits seem to represent a specific phenotype in
adolescents with FHA [41].
At the CDI test, adolescents with FHA showed overall
higher scores than healthy controls but pathological
depressive traits were described only in two cases. These
two adolescents presented higher scores at the bulimia
subscale, and lower restrictive traits at EDI-2, being more
similar to the adult phenotype. Moreover, subjects with
FHA presented social insecurity and introversion, which

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 Author's personal copy
Fig. 1 Subjects with depressive traits at the CDI in the three groups.
*p = 0.000 (Pearson Chi-square test). AN anorexia nervosa, FHA
functional hypothalamic amenorrhea
Fig. 2 Subjects with traits of alexithymia at the TAS-20 in the three
groups. *p = 0.002 (Pearson Chi-square test). AN anorexia nervosa,
FHA functional hypothalamic amenorrhea
might explain their alexithymic traits and the difficulty in
describing feelings, as observed at the TAS-20 scale. All
these aspects might be correlated to the particular vulner-
ability to stress observed in adolescent and adult subjects
with FHA [33], which is determined by the co-occurrence
of genetic factors (nature) and of precocious adverse events
(nurture) [33, 41–43]. In fact, early life events might per-
manently influence the sensibility of the CRH-ACTH
systems, which mediate the expression of endocrine,
autonomic, behavioral and emotional responses to stress
[41].
The biological correlates of the susceptibility to life
events are the endocrine alterations observed in FHA that
are caused by the disruption of the hypothalamic–pituitary–
adrenal axis and the consequent consistent production of
stress hormones, such as CRH, ACTH and cortisol in
response to stress. Chronically elevated central CRH levels
seem to be associated with symptoms of anxiety and
depression [44, 45]. Not surprisingly, female teens with
FHA were characterized by a tendency to develop
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Eat Weight Disord
depressive traits. Recent studies showed that women with
subclinical eating disorders, low self-esteem and difficult in
recognizing and/or dealing with emotions and troubles,
have higher risk of developing an eating disorder [46]. One
possible hypothesis to explain the development of FHA
rather than AN might be that resilience or vulnerability to
environmental and personal factors could promote more or
less severe form of disorders. In fact, all the aspects
described in adolescents with FHA were also present, in a
more severe form, in the age-matched adolescents with
AN, in accord with the literature on AN [3, 4, 21]. The two
clinical groups showed some common maturity issues:
social insecurity and maturity fears were assessed not only
in the subjects with AN but also in the teens with FHA.
These observations might be explained by a common
subconscious fear of becoming an adult. According to this
hypothesis, amenorrhea could be, both in FHA and in AN,
the somatic expression of the attempt to stop the growing
up toward sexuality [47].
In our previous study [48], we found an increased
parasympathetic modulation both in AN and FHA adoles-
cents by the recording of a 24-h ambulatory 12-lead elec-
trocardiogram (ECG). All our findings suggested that AN
(restrictive type) and FHA lie on a clinical spectrum, in
which the former presented similar but more serious hor-
monal, autonomic and psychopathological characteristics
than the latter.
A ‘‘cross-disorder’’ perspective is probably needed to
explore the differences and the similarities between these
two conditions. The study of nature–nurture interplay, with
the definition of different endophenotypes and subpheno-
types, might represent an effort to cross the boundaries
between currently conceptualized disorders. In particular,
four areas have already been described as worthy of further
investigation as possible cross-diagnostic endophenotypes
[36] that characterize, in some cases, also adolescents with
FHA: (1) increased physical activity, which is one of the
common features of FHA, (2) dimension of temperament
(in particular, negative emotionality, which was observed
at CDI both in FHA and AN adolescents), (3) dimensions
reflecting weight concern (including drive for thinness),
and (4) impaired set shifting, which seems to be related to
the presence of obsessive compulsive traits [49].
Moreover, emotion recognition difficulties, attention
biases to social threat and difficulties in emotion regulation
represent other possible endophenotypes associated with
eating disorders [50], which might explain the similarities,
observed at the TAS-20, with regard to the alexithymic
features, between FHA and AN, in adolescence.
In conclusion, nature–nurture interplay and different
genetic, environmental and affective-relational loads in the
areas of certain endophenotypes (for instance, emotion
recognition difficulties, negative emotionality and drive for
 Author's personal copy
Eat Weight Disord
thinness) could explain why some patients prove to be
more vulnerable to a full eating disorder, rather than
developing FHA.
A limit of our study was the relatively small sample
enrolled and the lack of a study of the biological markers in
FHA, compared to AN and healthy controls. Future studies
should be addressed to delve into the complex multifac-
toriality of these two conditions and, if possible, to bridge
the gap between them. The study of the expression of the
endophenotypes described in eating disorders could
include, for example, the analysis of set shifting capacities
in adolescents with FHA. Moreover, with regard to the
therapeutic aspects, adolescents with FHA usually do not
undergo any psychological assessment and/or psychother-
apy because the parental and adolescents’ attention is
immediately focused on the organic-gynecological aspects
[51].
In conclusion, FHA can be considered as a model of a
psychosomatic disease [51] and it might require psycho-
therapy beyond other treatments. In fact, recovery from
FHA is generally the norm once accommodation to the
stressors takes place [3]. To fulfill patients’ needs, the
psychological profile for FHA needs to be systematically
characterized and abnormalities linked to their potentially
unique biochemical, hormonal, and brain functional
imaging characteristics [3]. Adolescents with FHA should
then be globally assessed and treated with a multidisci-
plinary approach, for both organic and psychological
aspects.
Conflict of interest On behalf of all authors, the corresponding
author states that there is no conflict of interest.
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