5.75 Prevalence of Connective Tissue–Related Symptoms in Children With Neurodevelopmental Disorders: Insights Supporting the Connectivome Theory

Objectives ASD, ADHD, and Tourette’s disorder (TD) exhibit overlapping neuropathological mechanisms, such as impaired brain connectivity. A more complete view of the alteration of connectivity that characterizes neurodevelopmental disorders both at the central and peripheral levels has recently been formulated through the “Connectivome Theory,” which is based on the role of connective tissue in the different organs. The objective of this study is to investigate the prevalence of symptoms arising from connective tissue alterations in individuals diagnosed with ASD, ADHD, or TD and to compare it with a sample of healthy controls. Methods A questionnaire investigating connective tissue–related symptoms was administered from December 2019 to January 2022 to the families of 120 children diagnosed with ASD (n = 48), ADHD (n = 36), and TD (n = 36) attending the Child Neuropsychiatry Outpatient Clinics of the University Hospital of Verona. The questionnaire was also administered to the families of a control group, composed of 44 typically developing children. The symptoms assessed by the questionnaire were: 1) striae rubre/skin irregularities/flushed skin; 2) excessive sweating of hands/feet; 3) back pain/transient limb muscle aches/chronic fatigue; 4) hip dysplasia/scoliosis/hunched back; 5) flat feet; 6) constipation/diarrhea/alternating bowel; 7) heartburn/gastroesophageal reflux/hiatus hernia; 8) use of orthodontic appliances; 9) tactile/visual/auditory/olfactory/gustatory hypersensitivity; and 10) myopia/drooping eyelids/eyelid ptosis. Results Mean ages of cases and controls were 10.1 (SD: 3.6) and 9.5 (SD: 2.5) years, respectively. Most of the cases (110 subjects, 91.7%) were males; controls were distributed in 22 (50.0%) males and 22 (50.0%) females. Of the 10 symptoms assessed, 7 were more prevalent in cases than controls. Despite the small sample, the difference in prevalence reaches statistical significance with regards to flat feet (cases 47.97% vs controls 13.64%; p = .001), hypersensitivity (cases 54.47% vs controls 18.18%; p = .001) and myopia (cases 16.26% vs controls 2.27%; p = .016). Conclusions This exploratory study indicates a likely association of connective tissue–related disorders in children with neurodevelopmental disorders. Further studies will aim to confirm this hypothesis and evaluate ASD, ADHD, and TD separately

A New Method to Evaluate Joint Hypermobility in Paediatric Patients with Neurodevelopmental Disorders: A Preliminary Study

Background/Objectives: Neurodevelopmental disorders (NDDs) include a wide range of conditions that develop during the formation of the central nervous system, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Tourette syndrome (TS) is another neurodevelopmental disorder characterised by motor and vocal tics, which often co-occurs with ASD and ADHD. This study explores the feasibility of assessing joint hypermobility in children with specific neurodevelopmental conditions by measuring both ankles' passive range of motion (pROM). Methods: This study involved children diagnosed with ASD, ADHD, and TS, aged 5 to 15 years, who were compared with a control group of healthy children. The Beighton and Brighton scores and the pROM of the left and right ankles were measured. Data were analysed using SPSS version 22.0 for Windows (IBM SPSS Statistics, Chicago, IL, USA). A total of 102 subjects participated in this study (72.52% male, with a mean age of 10.7 ± 2.2 years). The sample included 24 children with ASD, 27 with ADHD, 26 with TS, and 25 healthy controls. Results: The pROM of the right and left ankles showed a significant positive correlation with the Beighton and Brighton scores in children with NDDs (ASD, ADHD, and TS combined). A trend towards higher Beighton scores (≥6) was observed in the ADHD and TS groups, with significance found in the TS group (p = 0.013). The pROM of the right ankle was significantly higher in the ADHD (p = 0.021) and TS (p = 0.013) groups compared to the controls. Although the left ankle followed a similar trend in the TS group, the difference was not statistically significant (p = 0.066). Controlling for age, the diagnosis of ASD, ADHD, and TS does not appear to impact any of the variables examined. Conclusions: There is a trend towards a higher prevalence of individuals with elevated Beighton scores in the ADHD and TS groups, suggesting greater general flexibility or hypermobility in these patients. However, the pROM of the right ankle is significantly higher in the ADHD and TS groups, with solid evidence in the TS group. These findings were not observed in children with ASD. However, it is necessary to consider the measurements obtained in relation to the patients' age. Finally, given that the pROM of the ankles correlates with the Beighton and Brighton scores, it could be utilised for the initial screening, monitoring, and follow-up of JH in some children with NDDs. Further investigations are required

Editorial: The “Connectivome Theory”: psyche, soma and the systemic involvement of connective tissue in neurodivergence

The Research Topic “The‘Connectivome Theory’: Psyche, Soma and the Systemic Involvement of Connective Tissue in Neurodivergence” explores the interactions between the different body systems according to the interpretative model of the “Connectivome Theory” (Zoccante et al.), identifying the connective tissue as the common element that could provide an explanation regarding the coexistence of functional alterations in multiple organs in neurodivergences and particularly in autism spectrum disorde

Neurodevelopmental Disorders and Connective Tissue-Related Symptoms: An Exploratory Case-Control Study in Children

Background/Objectives: Autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS) are neurodevelopmental disorders (NDDs) with overlapping symptoms, suggesting a partially shared genetic origin. This study investigates the prevalence of connective tissue-related conditions in individuals with ASD, ADHD, or TS. Methods: A questionnaire was administered to families of 120 individuals with ASD, ADHD, or TS, collecting sociodemographic data and examining 10 types of disorders affecting various organs and systems. Statistical analyses were performed using STATA 16.0, with the significance level set at 5%. Results: Among the 120 patients, 48 had ASD, 36 had ADHD, and 36 had TS. Flat feet were significantly more common in individuals with ASD (52.1%; OR 7.20; p < 0.001), ADHD (52.8%; OR 6.73; p = 0.001), and TS (38.9%; OR 3.70; p = 0.034) compared to controls (13.6%). Hypersensitivity was more frequent in individuals with ASD (56.3%; OR 5.90; p = 0.001), ADHD (50.0%; OR 4.11; p = 0.011), and TS (58.3%; OR 5.35; p = 0.003) compared to controls (18.2%). Myopia and ptosis were more common in ADHD (30.6%). There was a possible trend towards orthodontic device use in TS (OR 3.20; p = 0.076). Flat feet and hypersensitivity were also common in fathers (31.0% and 36.4%, respectively), mothers (31.0% and 15.2%), and patients (43.8% and 55%). Conclusions: The findings of this study highlight the significant associations between ASD, ADHD, and TS and specific physical symptoms, such as flat feet, sensory hypersensitivity, and other connective tissue-related manifestations. The familial prevalence of these symptoms suggests a potential genetic underpinning, further supporting the hypothesis of shared aetiological pathways. These insights underscore the need for interdisciplinary research to explore the mechanisms linking neurodevelopmental and connective tissue disorders, aiming to improve diagnosis and management strategies

Circulating Activated Platelets in Children With Long Covid: A Case-Controlled Preliminary Observation

We investigated if children with Long Covid (n=14) have activated platelets compared with healthy controls (n=14). Platelet activation and secretion markers were investigated by flow cytometry using MoAbs directed against P-selectin, CD63, and PAC-1 in quiescent platelets and in platelets stimulated with 10-μM adenosine diphosphate and 25-μM protease activated receptor 1-activating peptide. Circulating platelets of patients with Long Covid had significantly increased expression of the activation marker cytometry using MoAbs directed against P-selectin (P = 0.019)

Investigating gait, movement, and coordination in children with neurodevelopmental disorders: is there a role for motor abnormalities in atypical neurodevelopment?

Motor abnormalities have been suggested to play a role in most neuropsychiatric disorders, as a potential generic neurodevelopmental vulnerability. However, they still represent a neglected area, with a paucity of empirical studies, especially in pediatric populations. This case-control study aimed to comprehensively assess motor functioning in children with atypical neurodevelopment and investigate whether any socio-demographic or clinical characteristics would concur with motor difficulties to distinguish children with neurodevelopmental disorders (NDD) from healthy controls. Socio-demographic (age and gender) and clinical (intelligence quotient, gait, movement, and coordination) data were collected on 114 children aged 5-15 (83 with NDD, 31 healthy controls). Male children were at significantly higher risk for NDD (OR: 13.023, p < 0.001). Furthermore, there was a statistically significant interaction between the total intelligence quotient and overall coordination such that increasing levels of total intelligence quotient appeared to protect against the likelihood of being diagnosed with an NDD, but only in the context of a preserved coordination (OR: 0.964, p = 0.038). Collectively, results may have important public health implications, as they point towards the development of new approaches to establish an early prognosis in neurodevelopment, including assessing motor difficulties and mitigating their impact on children's quality of life

Effectiveness of equine-assisted activities and therapies for improving adaptive behavior and motor function in autism spectrum disorder

Equine-assisted activities and therapies (EAAT) have been suggested to improve adaptive behavior, and possibly motor function, in autism spectrum disorder (ASD). This study investigated the effects of EAAT on adaptive behavior and motor function in 15 children with ASD (13 males) aged 7-15 years as well as the impact of EAAT on the magnitude of stress in the parent-child system and the evolution in the child interaction with both the trained therapist and the therapeutic animal through the 20 weekly sessions of EAAT. EAAT were associated with greater adaptive behavior and coordination (all p 64 0.01) as well as a progressive improvement in the child's abilities to respond to the increasing complexity of such form of positive behavioral support (all p < 0.001). However, EAAT did not prove to be effective in reducing parental distress. Collectively, preliminary evidence presented here may have important public health implications and gives reason to hope that EAAT could possibly be an effective option in ASD, warranting further investigation of its potential benefits in clinical trials among larger samples

Postural control in childhood: investigating the neurodevelopmental gradient hypothesis

Neurodevelopmental disorders (NDDs) have been suggested to lie on a gradient continuum, all resulting from common brain disturbances, but with different degrees of impairment severity. This case-control study aimed to assess postural stability against such hypothesis in 104 children/adolescents aged 5-17, of whom 81 had NDDs and 23 were healthy controls. Compared to healthy controls, Autism Spectrum Disorder (ASD) resulted in the most severely impaired neurodevelopmental condition, followed by Attention Deficit Hyperactive Disorder (ADHD) and Tourette Syndrome (TS). In particular, while ASD children/adolescents performed worse than healthy controls in a number of sensory conditions across all parameters, ADHD children/adolescents performed worse than healthy controls only in the sway area for the most complex sensory conditions, when their vision and somatosensory functions were both compromised, and performance in Tourette Syndrome (TS) was roughly indistinguishable from that of healthy controls. Finally, differences were also observed between clinical groups, with ASD children/adolescents, and to a much lesser extent ADHD children/adolescents, performing worse than TS children/adolescents, especially when sensory systems were not operationally accurate. Evidence from this study indicates that poor postural control may be a useful biomarker for risk assessment during neurodevelopment, in line with predictions from the gradient hypothesis