Sophie Çabal-Berthoumieu

Bio: Sophie Çabal-Berthoumieu is an academic researcher. The author has contributed to research in topics: Child development & Emotional expression. The author has an hindex of 2, co-authored 4 publications receiving 108 citations.

The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader-Willi Syndrome.

Abstract: BACKGROUND AND OBJECTIVES: Patients with Prader–Willi syndrome (PWS) display poor feeding and social skills as infants and fewer hypothalamic oxytocin (OXT)-producing neurons were documented in adults. Animal data demonstrated that early treatment with OXT restores sucking after birth. Our aim is to reproduce these data in infants with PWS. METHODS: We conducted a phase 2 escalating dose study of a short course (7 days) of intranasal OXT administration. We enrolled 18 infants with PWS under 6 months old (6 infants in each step) who received 4 IU of OXT either every other day, daily, or twice daily. We investigated the tolerance and the effects on feeding and social skills and changes in circulating ghrelin and brain connectivity by functional MRI. RESULTS: No adverse events were reported. No dose effect was observed. Sucking assessed by the Neonatal Oral-Motor Scale was abnormal in all infants at baseline and normalized in 88% after treatment. The scores of Neonatal Oral-Motor Scale and videofluoroscopy of swallowing significantly decreased from 16 to 9 (P CONCLUSIONS: OXT is well tolerated in infants with PWS and improves feeding and social skills. These results open perspectives for early treatment in neurodevelopment diseases with feeding problems.

Prader-Willi Syndrome as a Model of Human Hyperphagia

Abstract: Prader-Willi syndrome (PWS), first described in 1956, is considered as a paradigm of a neurodevelopmental disorder with severe and early obesity with hyperphagia and impaired satiety The improved knowledge in the natural history and recent data on genetics offer new perspectives for understanding the metabolic and endocrine dysfunctions and possibly for treatment Natural history of the disease has been described due to the early diagnosis performed in the first months of life and various nutritional phases have been described In addition, there is clear evidence that the abnormal feeding behavior is included in the behavioral problems Brain imaging studies have shown that some brain regions may be important in PWS The role of SNORD116 gene cluster is detailed and its links with circadian rhythm and brain and hypothalamus development Pathophysiology of the abnormal ghrelin levels and of OT dysfunction is documented While no effect on appetite and weight regulation has been reported with ghrelin antagonists, OT has been shown to improve some of the behavioral problems in adults We discuss our hypothesis of an abnormal ghrelin/OT/dopamine pathway which may explain the switch of nutritional phases and behavior These new aspects offer an opportunity for therapeutic use and possible early intervention

Equivocal expression of emotions in children with Prader-Willi syndrome: what are the consequences for emotional abilities and social adjustment?

Abstract: People with Prader-Willi Syndrome (PWS) experience great difficulties in social adaptation that could be explained by disturbances in emotional competencies. However, current knowledge about the emotional functioning of people with PWS is incomplete. In particular, despite being the foundation of social adaptation, their emotional expression abilities have never been investigated. In addition, motor and cognitive difficulties - characteristic of PWS - could further impair these abilities. To explore the expression abilities of children with PWS, twenty-five children with PWS aged 5 to 10 years were assessed for 1) their emotional facial reactions to a funny video-clip and 2) their ability to produce on demand the facial and bodily expressions of joy, anger, fear and sadness. Their productions were compared to those of two groups of children with typical development, matched to PWS children by chronological age and by developmental age. The analyses focused on the proportion of expressive patterns relating to the target emotion and to untargeted emotions in the children’s productions. The results showed that the facial and bodily emotional expressions of children with PWS were particularly difficult to interpret, involving a pronounced mixture of different emotional patterns. In addition, it was observed that the emotions produced on demand by PWS children were particularly poor and equivocal. As far as we know, this study is the first to highlight the existence of particularities in the expression of emotions in PWS children. These results shed new light on emotional dysfunction in PWS and consequently on the adaptive abilities of those affected in daily life.

Dyssynchrony and perinatal psychopathology impact of child disease on parents-child interactions, the paradigm of Prader Willi syndrom.

Abstract: Background Infant-mother interaction is a set of bidirectional processes, where the baby is not only affected by the influences of his caregiver, but is also at the origin of considerable modifications. The recent discovery of biological correlates of synchrony during interaction validated its crucial value during child development. Here, we focus on the paradigmatic case of Prader-Willi Syndrome (PWS) where early endocrinal dysfunction is associated with severe hypotonia and early feeding disorder. As a consequence, parent-infant interaction is impaired. In a recent study (Tauber et al., 2017), OXT intranasal infusion was able to partially reverse the feeding phenotype, infant’s behavior and brain connectivity. This article details the interaction profile found during feeding in these dyads and their improvement after OXT treatment. Methods Eighteen infants (≤6 months) with PWS were recruited and hospitalized 9 days in a French reference center for PWS where they were treated with a short course of intranasal OXT. Social withdrawal behavior and mother-infant interaction were assessed on videos of feeding before and after treatment using the Alarm Distress Baby (ADBB) Scale and the Coding Interactive Behavior (CIB) Scale. Raters were blind to treatment status. Results At baseline, infants with PWS showed hypotonia, low expressiveness of affects, fatigability and poor involvement in the relationship with severe withdrawal. Parents tended to adapt to their child difficulties, but the interaction was perturbed, tense, restricted and frequently intrusive with a forcing component during the feeding situation. After OXT treatment, infants were more alert, less fatigable, more expressive, and had less social withdrawal. They initiated mutual activities and were more engaged in relationships through gaze, behavior, and vocalizations. They had a better global tonicity with better handling. These modifications helped the parents to be more sensitive and the synchrony of the dyad was in a positive transactional spiral. Conclusion Dys-synchrony can be induced by children’s pathology as well as parental pathology with emotional and developmental impact in the both cases. The PWS paradigm shows us the necessity to sustain early parents-child relationship to avoid establishment of a negative transactional pattern of interaction that can impact child’s development.

What underlies emotion regulation abilities? An innovative programme based on an integrative developmental approach to improve emotional competencies: Promising results in children with Prader–Willi syndrome

Abstract: Background This study aimed to test the effect of a new training programme on emotional competencies, named EMO-T, and to show the value of an integrative developmental approach. This approach postulates that the emotion regulation disturbances commonly observed in neurodevelopmental disorders are the consequence of potential disruptions in the prerequisite emotion skills. This integrative approach is particularly suitable in the case of complex and multidimensional disorders such as Prader–Willi syndrome (PWS), a rare genetic disease. Methods We examined the emotion expression, recognition, comprehension, and regulation skills in 25 PWS children aged 5–10 and 50 typically developing children (TD) aged 3–10. After a pre-test session, half of the PWS children participated in the EMO-T programme with their regular therapist for 6 weeks, while the other half continued their usual rehabilitation programme. Two post-test sessions were conducted, one at the end of the programme and one 3 months later. Results At pre-test, PWS children displayed a deficit in the four emotional competencies (EC). PWS children who participated in the EMO-T programme showed a significant and sustainable post-test improvement regarding voluntary expression and emotion recognition abilities, such that the level reached was no longer different from the baseline level of TD children. They also tended to improve in their emotion regulation, although they received no specific training in this skill. Discussion These results support that emotion regulation abilities require prerequisite emotion skills, which should be more fully considered in current training programmes. Because emotion regulation disorders strongly impact all areas of life, an integrative developmental approach appears crucial especially in the case of neurodevelopmental disorders. Further studies should be conducted to explore this perspective.

Genetic and epigenetic causes of obesity.

Abstract: Obesity is a complex, heritable trait influenced by the interplay of genetics, epigenetics, metagenomics and the environment. With the increasing access to high precision diagnostic tools for genetic investigations, numerous genes influencing the phenotype have been identified, especially in early onset severe obesity. This review summarizes the current knowledge on the known genetic causes of obesity and the available therapeutic options. Furthermore, we discuss the role and potential mechanism of epigenetic changes that may be involved as mediators of the environmental influences and that may provide future opportunities for intervention.

Ontogenesis of oxytocin pathways in the mammalian brain: late maturation and psychosocial disorders.

Abstract: Oxytocin (OT), the main neuropeptide of sociality, is expressed in neurons exclusively localized in the hypothalamus. During the last decade, a plethora of neuroendocrine, metabolic, autonomic and behavioral effects of OT has been reported. In the urgency to find treatments to syndromes as invalidating as autism, many clinical trials have been launched in which OT is administered to patients, including adolescents and children. However, the impact of OT on the developing brain and in particular on the embryonic and early postnatal maturation of OT neurons, has been only poorly investigated. In the present review we summarize available (although limited) literature on general features of ontogenetic transformation of the OT system, including determination, migration and differentiation of OT neurons. Next, we discuss trajectories of OT receptors (OTR) in the perinatal period. Furthermore, we provide evidence that early alterations, from birth, in the central OT system lead to severe neurodevelopmental diseases such as feeding deficit in infancy and severe defects in social behavior in adulthood, as described in Prader-Willi syndrome (PWS). Our review intends to propose a hypothesis about developmental dynamics of central OT pathways, which are essential for survival right after birth and for the acquisition of social skills later on. A better understanding of the embryonic and early postnatal maturation of the OT system may lead to better OT-based treatments in PWS or autism.

Early diagnosis and care is achieved but should be improved in infants with Prader-Willi syndrome

Abstract: PWS is a severe neurodevelopmental genetic disorder now usually diagnosed in the neonatal period from hypotonia and feeding difficulties. Our study analyzed the birth incidence and care of infants with early diagnosis. Data were collected on 61 infants with a molecular diagnosis of PWS born in 2012 and 2013 in France. Thirty-eight infants with PWS were born in 2013. The median age at diagnosis was 18 days. Birth incidence calculated for 2013 was 1/21,000 births. No case was diagnosed prenatally, despite 9 amniocenteses, including 4 for polyhydramnios. Five infants had delayed diagnosis, after 3 months of life. For 2 of them, the diagnosis was not suspected at birth and for 3, FISH analysis in the neonatal period was normal, with no further molecular studies. Ninety-three percent of the neonates were hospitalized, and 84% needed nasogastric tube feeding for a median of 38 days. Swallowing assessment was performed for 45%, at a median age of 10 days. Physiotherapy was started for 76% during hospitalization. Eighty percent of those diagnosed within the first 3 months were seen by a pediatric endocrinologist within the first week of life. Our study is the first to assess the birth incidence of PWS in France, at 1/21,000 births. Some prenatal or neonatal cases remain undiagnosed because of unrecognized clinical signs and the inappropriate choice of the initial molecular test. We also underscore the need to optimize neonatal care of infants with PWS.

Obesity management in Prader-Willi syndrome: current perspectives.

Abstract: Prader-Willi syndrome (PWS) is a complex multisystem disorder due to the absent expression of the paternally active genes in the PWS critical region on chromosome 15 (15q11.2-q13). The syndrome is considered the most common genetic cause of obesity, occurring in 1:10,000-1:30,000 live births. Its main characteristics include neonatal hypotonia, poor feeding, and lack of appetite in infancy, followed by weight gain, lack of satiety, and uncontrolled appetite, frequently after the age of 2-3 years. The clinical picture includes short stature, multiple endocrine abnormalities (hypogonadism, growth hormone/insulin-like growth factor-I axis dysfunction, hypothyroidism, central adrenal insufficiency), dysmorphic features, scoliosis, osteoporosis, mental retardation, and behavioral and psychiatric problems. Subjects with PWS will become severely obese unless their food intake is strictly controlled. Constant and obsessive food seeking behavior can make life very difficult for both the family and caretakers. Prevention of obesity is mandatory in these patients from the first years of life, because once obesity develops it is difficult to maintain the control of food intake. In fact, PWS subjects die prematurely from complications conventionally related to obesity, including diabetes mellitus, metabolic syndrome, sleep apnea, respiratory insufficiency, and cardiovascular disease. The mechanisms underlying hyperphagia in PWS are not completely known, and to date no drugs have proven their efficacy in controlling appetite. Consequently, dietary restriction, physical activity, and behavior management are fundamental in the prevention and management of obesity in PWS. In spite of all available therapeutic tools, however, successful weight loss and maintenance are hardly accomplished. In this context, clinical trials with new drugs have been initiated in order to find new possibilities of a therapy for obesity in these patients. The preliminary results of these studies seem to be encouraging. On the other hand, until well-proven medical treatments are available, bariatric surgery can be taken into consideration, especially in PWS patients with life-threatening comorbidities.