Preliminary findings on the association between attachment patterns
and levels of growth hormone in a sample of children
with non-organic failure to thrive

Risultati preliminari sull’associazione tra stili di attaccamento e livelli di ormone
della crescita in un campione di bambini affetti da deficit di crescita
non organico


1Department of Neurology and Psychiatry, Sapienza University of Rome, Italy
2Department of Experimental Medicine, Section of Medical Pathophysiology and Endocrinology, Sapienza University of Rome, Italy

SUMMARY. Introduction. Deficiency of growth hormone (GH) in absence of pituitary injuries is one of the causes of short stature and of the non organic failure to thrive (NOFTT) condition. Advances in developmental psychology have highlighted the role of emotions and caregiving behaviors in the organization of child’s personality and psychobiology, with the mother-son attachment bond being considered a fundamental developmental experience. The objective of the present preliminary study was to assess whether there are significant correlations between attachment patterns and GH levels in a sample of subjects with NOFTT. Methods. Overall, 27 children (mean age 9.49±2.63 years) with NOFTT were enrolled. Perceived attachment security was assessed through the Security Scale (SS) and its subscales focused on maternal and paternal security. Pearson partial correlation was used to test associations between GH levels and SS measures adjusting for confounding factors (i.e. age, gender and body mass index). Results. Across all subjects, GH was significantly positively correlated with general security (r=0.425; p=0.038) and maternal security (r=0.451; p=0.027) and not significantly correlated with paternal security (r=0.237; p=0.264). Discussion. These findings preliminarily suggest that the association between GH levels and perceived attachment security may play a role in the pathophysiology of NOFTT and add to the accumulating evidence that attachment patterns may be related with specific psychoendocrine underpinnings.

KEY WORDS: growth hormone, non organic failure to thrive, children, attachment style.

RIASSUNTO. Introduzione. La riduzione dell’ormone della crescita (GH) in assenza di lesioni ipofisarie è una delle cause di bassa statura e della condizione clinica di deficit di crescita non organico, nota come “non-organic failure to thrive” (NOFTT). I progressi nell’ambito della psicologia dello sviluppo hanno messo in evidenza il ruolo delle emozioni e dei comportamenti del caregiver nell’organizzazione della personalità e della psicobiologia del bambino, considerando il legame di attaccamento madre-figlio come un’esperienza fondamentale nello sviluppo. Il presente studio preliminare si pone come obiettivo quello di valutare l’esistenza di correlazioni significative tra modelli di attaccamento e livelli di GH in un campione di soggetti affetti da NOFTT. Metodi. Sono stati arruolati nello studio 27 bambini (età media: 9,49±2,63) con NOFTT. La sicurezza della percezione di attaccamento è stata valutata attraverso la Scala di Sicurezza (SS) e le sottoscale inerenti il grado di sicurezza materna e paterna. La correlazione parziale di Pearson è stata usata per indagare le associazioni tra i livelli di GH e le misure SS, covariando per i fattori confondenti (ossia età, sesso e BMI). Risultati. In tutti i soggetti, il valore di GH era positivamente correlato in modo statisticamente significativo alla percezione della sicurezza generale (r=0,425; p=0,038) e della sicurezza materna (r=0,451; p=0,027) e non significativamente correlato con la sicurezza paterna (r=0,237, p=0,264). Discussione. Questi dati suggeriscono preliminarmente che l’associazione tra i livelli di GH e la sicurezza nella percezione dell’attaccamento possano svolgere un ruolo nella fisiopatologia del NOFTT, e si aggiungono al filone di evidenze inerenti il fatto che certi modelli di attaccamento possano essere associati a condizioni psico-endocrine specifiche.

PAROLE CHIAVE: ormone della crescita, deficit di crescita non organico, bambini, stile di attaccamento.

The term “failure to thrive” (FTT) includes a heterogeneous range of clinical conditions phenotypically characterized by inadequate growth or inability to maintain growth (i.e. <160 cm height in males and <149 cm height in females), usually in early childhood1.
Traditionally, the causes of FTT have been divided into organic (medical) and non-organic (social or environmental)2. Increasing evidence suggests that in many children the etiology of FTT is multifactorial, including biological, psychosocial, and environmental contributors3. Epidemiological researches have shown that only 20-25% of infants and children with FTT receive the diagnosis of organic FTT (OFTT), while in the majority of cases it is not possible to identify a specific organic cause of FTT (i.e. the so-called non-organic FTT - NOFTT)4. The condition of NOFTT does not fulfill the criteria for being considered a medical diagnosis, but rather it represents a standardized description of a pattern of growth4.
In absence of clear organic causes, i.e. in the condition of NOFTT, several different psychosocial conditions may play a role in explaining the FTT phenotype, such as children’s impaired affect regulation and temperamental characteristics, inadequate children’s nutritional intake, a vicious circle of maladaptive behavioral interaction between caregiver and infant, caregivers’ unsure attachment styles, psychosocial stress and psychopathology5.
Advances in developmental psychology have highlighted the role of emotions and caregiving behaviors in the organization of children’s personality and psychobiology, with the mother-son attachment bond being considered a fundamental developmental experience6,7. According to the attachment theory, attachment styles have typically been classified into three types: secure, anxious, and avoidant7,8. These types not only describe individual’s behavioral patterns but also represent the organization through the expectations of others in response to comfort or reassurance seeking7,8. The early attachment characteristics have been shown to play an important role in influencing psychopathological outcomes in adulthood9, and the presence of insecure attachment (i.e. anxious or avoidant) in children has been suggested to increase vulnerability towards several psychiatric diseases10. Further, preliminary studies evidenced a link between attachment styles and certain patterns of endocrine and immune functions11-15.
Early studies exploring the conditions of childhood emotional deprivation and mistreatments had identified a syndrome defined as “psychosocial dwarfism” or “reversible hypopituitarism syndrome” characterized by short stature often associated with a reversible deficit of growth hormone (GH) and with a range of psychiatric and behavioural disturbances such as eating disorders, insomnia, depression, bedwetting, poor cognitive performance16. The authors postulated that the emotional deprivation could act on the hypothalamus-pituitary gland and alter the release of GH as well as of somatomedins and other endocrine factors16.
Reduced levels of GH (i.e. pituitary dwarfism or GH deficiency - GHD) in absence of pituitary injuries are nowadays considered one of the causes of NOFTT17. The objective of the present preliminary study was to assess, for the first time in psychoendocrinological research, whether there are significant correlations between patterns of attachment and GH levels in a sample of subjects with NOFTT. A deeper understanding of psychobiological correlates of NOFTT could potentially lead to the development of better diagnostic and therapeutic strategies for individuals with this condition.
Recruitment procedures and study participants
The institutional review board of Sapienza University of Rome approved the study. All subjects provided written, informed consent prior to commencing their involvement in the trial.
Patients with NOFTT (characterized by short stature or reduced annual growth rate) were recruited among those attending the Centre for the Diagnosis and Therapy of GHD at the Department of Experimental Medicine of Policlinico Umberto I University Hospital (Rome, Italy).
The following auxological criteria were considered as inclusion criteria: (i) age range between 6 and 15 years, (ii) stature <3 SD or stature <2 SD from the mean value, and (iii) annual growth velocity <1 SD from the mean value evaluated after at least 6 months of clinical observation.
The exclusion criteria were: (i) presence of any chronic systemic disease (malabsorption syndrome, Fanconi anemia, cardiac, renal and metabolic disorders), (ii) endocrine and psychiatric disorders diagnosed according to DSM-518, (iii) use of any pharmacological therapy, (iv) presence of brain and pituitary injuries as assessed by cerebral magnetic resonance imaging.
Each patient underwent blood examinations to measure GH levels and psychopathological evaluation (through the Security Scale - SS) to assess attachment. The SS is a self-report measure which assesses children’s perceptions of security in parent-child relationships and consists in 15 items19. The SS has two sets of specular items focused on the attachment relationship about their mothers and their fathers, in order to get an overall picture of children’s attachment perception. The instrument assesses to which degree children perceive their parents as being responsive and available, their tendency to rely on them in times of distress and their ease and interest in communicating with their parents. Each item is scored from 1 to 4, with higher scores representing greater perception of attachment security. The SS has three subscales: the first subscale assesses the degree of security perception in mother-child relationship (SSPSM); the second subscale assesses the degree of security perception in father-child relationship (SSPSP); the third subscale is derived from the sum of the two previously described subscales and assesses the overall perception of security (SSPSC). Serum GH levels were measured using immunoradiometric assays 6.
Statistical analyses
All tests were 2-tailed with an α=0.05. GH was non-normally distributed, thus it was transformed using Ln transformation. Pearson partial correlation was used to test correlations between GH and the assessment measures of attachment (i.e. SSPSM, SSPSP and SSPSC) adjusting for age, gender and body mass index (BMI; weight in kilograms divided by the square of height in meters) because of (i) their known associations with GH secretion and function, and (ii) the significant inverse correlations between age and GH (r=-0.485; p=0.010) observed in our sample.
Overall, 21 males and 6 females (mean age 9.49±2.63 years) were included in the study. Among them, 19 patients had NOFTT associated with non-organic GHD, while 8 patients had NOFTT not associated with GHD. Demographic and clinical characteristics of the subjects are presented in Table 1.
Across all subjects, GH was significantly positively correlated with SSPSM (r=0.451; p=0.027) and SSPSC (r=0.425; p=0.038) (Figure 1) and not significantly correlated with SSPSP (r=0.237; p=0.264).

To the best of our knowledge, this is the first study testing the association between GH levels and psychological measures of attachment in a sample of children with NOFTT. The results of this preliminary investigation showed a significant positive correlation between GH levels and perceptions of children’s attachment to their parents in terms of partial scores (attachment to the mother) and of total scores (mother and father). The correlation was not significant for the perception of attachment to the father.
Our findings are consistent with previous evidence suggesting a link between early affective dysregulation, altered physical development and the condition of NOFTT11,12, and add specificity to this field of exploration through (i) the quantitative measurement of GH levels and the degree of perceived attachment, and (ii) the enrollment of children who were not using any medication, thus with low levels of biological confounders. Further, our findings add to the accumulating evidence suggesting meaningful associations of attachment patterns with endocrine and immune functions20,21.
In the reported significant relationship between GH levels and perceived security of attachment, both the directions of causality may be postulated. On the one hand, it is possible that the degree of perceived attachment towards the parents can contribute to psychobiologically affect the functioning of the hypothalamic-pituitary-adrenal axis with subsequent hormonal alterations of GH levels. On the other hand, it is possible that the conditions of less efficient endocrine functioning and short stature in children can induce anxiety in their parents that might interfere with reliable and consistent parenting and thus facilitate a maladaptive development of inter-personal relationships in children.
The major limitation of the present preliminary study is the small sample size, which partially results from the rarity of the NOFTT clinical condition. Future studies, including ongoing projects of our research team, will need to include a larger number of subjects, a control group, and a more comprehensive set of explored psychopathological and endocrine assessments. Overall, these preliminary findings suggest that the association between GH levels and perceived attachment security may play a role in the pathophysiology of NOFTT and add to the accumulating evidence that attachment patterns may be related with specific psychoendocrine underpinnings.

Conflict of interest: none declared.
 1. Bartke A. Growth hormone and aging: a challenging controversy. Clin Interv Aging 2008; 3: 659-65.
 2. Shields B, Wacogne I, Wright CM. Weight faltering and failure to thrive in infancy and early childhood. BMJ 2012; 345: 5931.
 3. Ross E, Munoz FM, Edem B, et al.; Brighton Collaboration Failure to Thrive Working Group. Failure to thrive: case definition and guidelines for data collection, analysis, and presentation of maternal immunisation safety data. Vaccine 2017; 35 (48 Pt A): 6483-649.
 4. Kim HS, Yang SW, Yoo HW, et al. Efficacy of short-term growth hormone treatment in prepubertal children with idiopathic short stature. Yonsei Med J 2014; 55: 53-60.
 5. Benoit D, Zeanah CH, Parker KC, Nicholson E, Coolbear J. Working model of the child interview: infant clinical status related to maternal perceptions. Infantal Mental Health Journal 1997; 18: 107-21.
 6. Mokhtar M. Effect of attachment on early and later development. British Journal of Developmental Disabilities 2007; 53 (Part 2): 81-95.
 7. Van Rosmalen L, van der Horst FC, van der Veer R. From secure dependency to attachment: Mary Ainsworth’s integration of Blatz’s security theory into Bowlby’s attachment theory. Hist Psychol 2016; 19: 22-39.
 8. Corcoran M, McNulty M. Examining the role of attachment in the relationship between childhood adversity, psychological distress and subjective well-being. Child Abuse Negl 2017; 76: 297-309.
 9. Aceti F, Baglioni V, Ciolli P, et al. Maternal attachment patterns and personality in post partum depression. Riv Psichiatr 2012; 47: 214-20.
10. Hendaus M, Al-Hammadi A. Failure to thrive in infants. Georgian Med News 2013; 214: 48-54.
11. Maunder RG, Hunter JJ. Attachment and psychosomatic medicine: developmental contributions to stress and disease. Psychosom Med 2001; 63: 556-67.
12. Togut MR, Allen JE, Lelchuck L. A psychological exploration of the nonorganic failure-to-thrive syndrome. Dev Med Child Neurol 1969; 11: 601-7.
13. Rocchi G, Serio V, Carluccio GM, et al. Early attachment relationships and epigenetic customization. Riv Psichiatr 2015; 50: 155-60.
14. Picardi A, Miglio R, Tarsitani L, et al. Attachment style and immunity: a 1-year longitudinal study. Biol Psychol 2013; 92: 353-8.
15. Picardi A, Battisti F, Tarsitani L, et al. Attachment security and immunity in healthy women. Psychosom Med 2007; 69: 40-6.
16. Mouridsen SE, Nielsen S. Reversible somatotropin deficiency (psychosocial dwarfism) presenting as conduct disorder and growth hormone deficiency. Dev Med Child Neurol 1990; 32: 1087-104.
17. Jaffe AC. Failure to thrive: current clinical concepts. Pediatr Rev 2011; 32: 100-7.
18. Biondi M, Bersani FS, Valentini M. The Italian edition of DSM-5. Riv Psichiatr 2014; 49: 57-60.
19. Kerns KA, Klepac L, Cole A. Peer relationships and preadolescents’ perceptions of security in the child-mother relationship. Dev Psychol 1996; 32: 457-66.
20. Kidd T, Hamer M, Steptoe A. Examining the association between adult attachment style and cortisol responses to acute stress. Psychoneuroendocrinology 2011; 36: 771-9.
21. Oskis A, Loveday C, Hucklebridge F, Thorn L, Clow A. Anxious attachment style and salivary cortisol dysregulation in healthy female children and adolescents. J Child Psychol Psychiatry 2011; 52: 111-8.