1. Introduction
Among the many challenges associated with the diagnosis and treatment of childhood dwarfism, mental health and psychological functioning are of particular concern. Many believe that children and adolescents who are shorter in stature than their peers have impaired mental health and psychological dysfunction, and that growth hormone (GH) therapy may have a positive effect on this. However, there is considerable controversy regarding the nature and extent of this impairment in young patients with GH deficiency (GHD) and idiopathic dwarfism (ISS). How to confirm the diagnosis by testing GH in children with GHD and ISS is also a matter of concern in most European countries. These issues raise the question whether the addition of psychological criteria to the conventional endocrine and growth criteria can more effectively guide treatment decisions.
In order to answer this question, it is important to clarify the following issues: What kind of psychological problems can be caused by dwarfism? What is the level of awareness of these psychological problems among children and their parents, and how should they be assessed? Is there evidence that GH replacement therapy has psychological effects? Can the above findings be used to determine the criteria for treatment decisions?
2. Understanding psychological states
Psychology is a science of individual feelings and behaviors that provides different conceptual models and assessment methods for understanding the psychological states of children and adolescents with or without health problems. Although no comprehensive classification system exists for assessing the mental state of children and adolescents, a basic model can suggest much information, such as that health and functioning are related to emotional, cognitive, physical, and social life, and that both protective and risk factors can influence mental state.
Mental status is age-related in terms of controlling development and can be assessed by mental health, physical health, cognitive performance, and/or social skills. Assessment of the above indicators includes psychological tests for behavioral observations, clinical scales, parental reports, and self-reported outcomes in children and adolescents.
These above methods have seen some paradigm shifts in recent years. In addition to external or expert assessments of developmental progress and performance, there is a growing recognition of the importance of understanding how children and adolescents evaluate themselves and the issues affecting their mental health and psychological functioning in health, illness, and disability states. This new approach to subjective understanding of psychological functioning and mental health comes from the concept of health-related quality of life (QoL).
QoL is a multidimensional construct related to the basic components of health and functioning of a child or adolescent. External observers, including family members, teachers, or those providing medical care, can also provide relevant information; however, they only provide additional perspectives and cannot replace the child’s own reports.
QoL models identify physical, emotional, mental, social, and behavioral aspects of health and functioning. These models rely not only on the respective clinical characteristics of health problems and their treatment, but also on individual characteristics such as health behaviors, self-efficacy or self-coping, and on social factors such as life circumstances, socioeconomic status or access to health care.
Generic tools designed to assess QoL in children and adolescents have been developed in all health states as well as in specific diseases, especially for chronic disease measurement. The generic tools include the KIDSCREEN index. The KIDSCREEN Index consists of a generic core tool and several condition-specific modules, where the condition-specific module is used to assess QoL in children and adolescents with chronic diseases and the KIDSCREEN Index also includes parental perspectives.
A recent literature review found few studies of health-related QoL in young patients with ISS or GHD. Overall, the available studies provide more information on health status as assessed by the observer, especially related to mental health. Among them, the mental functioning of children with dwarfism is often assessed using the Achenbach Child Behavior Scale.
The following will answer the 4 key questions previously raised by the results of recent studies.
3. Psychological status of young patients with dwarfism
A review of the differences in the mental status of children and adolescents with different height ranges and clinical status is a prerequisite for determining treatment criteria. As a basis for decision making, empirical evidence regarding the expected benefit of treatment options is needed, where treatment options include but are not limited to GH replacement therapy.
Question 1: Do children with dwarfism have poorer mental health than normal children (height-for-age)?
Recent evidence comes from cohort studies that have incorporated measures of mental status. A retrospective cohort study using the General Health Status Measure in 14,460 adults in the UK found large height-related differences in QoL. However, these results were not supported in children. Among 712 children aged 11 years or older with dwarfism (i.e., height below the 10th percentile, n=28) or normal height (i.e., height above the 10th percentile, n=684), there were no differences in self-reported or teacher-reported social, emotional, or behavioral outcomes including feelings of depression, optimism, social support, or victimization.
A study conducted among 405 Korean elementary school students showed that children who were short were more dissatisfied with their own height, but the study did not observe differences between CBCL scores by height. In fact, both height and weight were non-significant predictors of CBCL scores, while in-school performance was correlated with CBCL scores.
In the WessexGrowth study, no differences were observed between young adults with dwarfism and young adults with normal height. Socioeconomic status, employment status and educational status had a greater effect on individual functioning than height.
Kurth et al. compared QoL for height increases in the range <-2SDS (i.e., shortest subjects) to >+2SDS (i.e., tallest subjects) by 0.5 SDS using data from the first nationally representative German health survey. analysis of variance revealed no statistically significant differences in spontaneously reported QoL between these increases. In addition, there was no difference in QoL between height ranges for children judged by their parents. The above results do not support the hypothesis that dwarfism is associated with lower QoL.
Question 2: What are the height-related psychological problems in children and adolescents with ISS or CHD?
In order to understand the magnitude of the correlation between psychological status and dwarf children and adolescents, the perspectives of the patients themselves and their family members need to be obtained. The Quality of Life in Adolescents with Dwarfism (QOLISSY) project group, composed of experts from 5 countries (Germany, UK, Spain, Sweden and France), was established to increase the knowledge of QoL in children with ISS. In particular, the QOLISSY was established to develop a comprehensive model of mental functioning and mental health that can be used as a cross-cultural detection tool to assess QoL reported by children and adolescents with dwarfism as well as parent-reported QoL.
First, QOLISSY collaborators in 5 countries conducted a panel discussion consisting of 24 children and their parents in 2 age groups (8 to 12 years and 13 to 18 years). The perspectives of the parents of the younger (i.e., 4 to 7 years old) children were also included, as well as the children’s own perspectives.
Discussion groups were moderated by the session chair and used interview guides to facilitate group discussions, record and collate group discussions, and qualitative analysis of the QoL questionnaire to produce reports. The panels were conducted in age- and treatment-specific groups in five countries, with a total of over 100 children and their parents. The panel categorized over 2,500 reports into five categories: emotional impact, social impact, physical impact, coping, and treatment. The social dimension was particularly prominent and included teasing, bullying and issues related to social exclusion, stigma and immaturity. However, social support, peer acceptance, and a positive outlook for the future were also reported. These data reveal elements that have not been covered by established generic measures and need to be included in a dwarfism-specific QoL instrument for young patients with ISS.
Question 3: What are the psychological state characteristics of young patients with dwarfism? What role does height play in this compared to other psychological determinants?
A study of psychological functioning in young adult patients with ISS or GHD showed that patient scores were comparable to the general population and that differences between those who had received treatment and those who did not were not significant. These results are similar to those of other studies suggesting that the psychological status of patients with ISS or GHD is not affected compared to those with normal height; however, differences were observed between patients with GHD and those with ISS. In Japanese children with CHD (n=127) or ISS (n=116) aged 4 to 15 years whose mental status was assessed by the spontaneous report form of CBCL, children with ISS had higher CBCL scores than controls of normal height and more behavioral problems than children with GHD.
Although clinical determinants of mental status in ISS or GHD have been examined, including age and gender, psychological modifiers, such as coping and social support, have not been examined. Few studies have attempted to model psychological functioning in patients with dwarfism that is dynamic and takes into account both risk and protective factors. Such empirically tested models would be very helpful in diagnosing psychological impairment, identifying patient needs and providing appropriate support, both medical and non-medical.
Question 4: Is there evidence that GH replacement therapy improves psychological status in children and adolescent patients with ISS or GHD?
Longitudinal observational studies, prospective interventional designs, or randomized clinical trials are needed to examine the psychological impact of GH replacement therapy in children and adolescent patients with ISS or CHD. Ross et al. found no correlation between dwarfism and problems related to psychological adjustment or self-concept. However, studies did observe improvements in behavioral functioning, such as lower CBCL scores, with improvements attributed to GH replacement therapy. visser-vanBalen et al. conducted a retrospective study of QoL in 30 children with ISS treated with GH combined with GnRH agonists for 3 years and found no difference between 18 treated and 12 untreated children differences.
A review of clinical studies that included psychological endpoints showed the opposite results. One study, using a generic questionnaire, showed no differences between children with ISS and the general population except for social skills, which had lower scores, and GH replacement therapy did not improve QoL. another study found no statistically significant differences between GH-treated children with ISS and controls on a variety of indicators such as perception of stress, body image, or coping with anger; however, in longitudinal comparisons within each group, the sexual characteristics and body image improved after receiving GH replacement therapy.
Other recent reviews have highlighted the lack of conclusive evidence of improvement in psychological status or psychological benefit of GH treatment. Given all the differences in metrics and study design, and the small sample size, it is not possible to draw major conclusions about the psychological benefits of GH treatment at this time.
4. Conclusions
Indicators of psychological status used to describe the dwarfism population and to assess the benefit of intervention at the individual level include assessments of physical effects, such as growth and strength, emotional effects, such as mental health and adjustment, and social effects, such as inclusion in peers and social support.
Medication is thought to improve QoL by stimulating growth, which in turn improves physical, emotional, and social functioning as well as mental health; however, QoL can also be improved through cognitive-behavioral therapies targeted at improving individual self-confidence and through social interventions such as coping skills or cognitive programs such as those for dwarfism.
In addition, we need conceptual models to identify relevant psychological criteria that specify the relationship between height and mental status and that take into account both risk and protective factors. Theoretically, these psychological criteria should be assessed using psychometrically tested methods for children and adolescents aged 6 years and older that are responsive to change. In order to assess the most meaningful psychological criteria for treatment decisions, we need classification methods or models that are applicable to psychological outcomes in the general population and in children with ISS. We also need more psychological studies related to the diagnosis and treatment of children with ISS or GHD in which the patients themselves and their parents are involved in making judgments.
QoL methods are suitable for research and clinical practice; however, longitudinal studies with sufficient sample sizes need to be included to assess the psychological status of patients with ISS. In addition to height, other determinants of mental status, such as weight and socioeconomic status, should be assessed, as these may also play a role in the patient’s perception of mental health and psychological functioning.