Global child and adolescent mental health perspectives: bringing change locally, while thinking globally.

Child and adolescent mental health (CAMH) are a global priority. Different countries across the globe face unique challenges in CAMH services that are specific to them. However, there are multiple issues that are also similar across countries. These issues have been presented in this commentary from the lens of early career CAMH professionals who are alumni of the Donald J Cohen Fellowship program of the IACAPAP. We also present recommendations that can be implemented locally, namely, how promoting mental health and development of children and adolescents can result in better awareness and interventions, the need to improve quality of care and access to care, use of technology to advance research and practices in CAMH, and how investing in research can secure and support CAMH professionals and benefit children and adolescents across the globe. As we continue to navigate significant uncertainty due to dynamic circumstances globally, bolstering collaborations by "bringing change locally, while thinking globally" are invaluable to advancing global CAMH research, clinical service provision, and advancement of the field.

Development and Psychometric Properties of the Multi-System Profile of Symptoms Scale in Patients with Rett Syndrome.

Background: Rett Syndrome (RTT) is a rare, neurodevelopmental disorder characterised by a range of problematic symptoms. There is yet to be a robust instrument to adequately capture the range of disease severity across the lifespan. In this study, we aimed to develop and assess the validity of an RTT-specific electronic Observer Reported Outcome (eObsRO), the Multi-System Profile of Symptoms Scale (MPSS). Methods: The study was conducted in two phases. Phase 1 consisted of a systematic literature review, focus groups, expert feedback, and a pilot test of the new scale. Modifications were made based on preliminary analysis and feedback collected in the pilot phase. Phase 2 consisted of the validation of the questionnaire based on two samples (Sample 1, n = 18; Sample 2, n = 106). Participants were all parents or caregivers of individuals with RTT. Results: The MPSS consists of 12 validated sub-scales (mental health problems, autonomic problems, cardiac problems, communication problems, problems in social behaviour, problems in engagement, gastrointestinal problems, problems in motor skills, neurological problems, orofacial problems, respiratory problems, and sleep problems), which explore symptom frequency in the past month and a supplement to the scale consisting of five sub-scales (sensory problems, immune dysfunction and infection, endocrine problems, skeletal problems, and dermatological problems), which is designed to capture symptom changes over a longer time period. The frequency of symptoms was rated on a 10-point slider scale, which then was automatically transformed into a 0 to 5 Likert score. All 12 sub-scales showed strong internal consistency (α ≥ 0.700) and good stability, ranging from 0.707 to 0.913. Pearson's correlation showed a statistically significant (r = 0.649) correlation between the MPSS and the Rett Syndrome Behaviour Questionnaire (RSBQ) total score and significant correlations between sub-scales with items that were presented in both the MPSS and RSBQ. Conclusions: The MPSS is a psychometrically validated eObsRO using the HealthTrackerTM platform and has the potential to be used in clinical trials.

An Observational Study of Heart Rate Variability Using Wearable Sensors Provides a Target for Therapeutic Monitoring of Autonomic Dysregulation in Patients with Rett Syndrome.

Rett Syndrome (RTT) is a complex neurodevelopmental disorder that has multi-system involvement with co-occurring epilepsy, breathing problems and autonomic dysregulation. Autonomic dysregulation can increase the risk of cardiorespiratory vulnerability in this patient group. Assessment of heart rate variability (HRV) provides an overview of autonomic health in RTT and offers insight into how the sympathetic and parasympathetic components of the nervous system function. However, to our knowledge, no study has evaluated HRV in Rett patients to assess how the dynamics of autonomic function vary with age and changes during the day and/or night. Using non-invasive wearable sensors, we measured HRV in 45 patients with RTT and examined the time and frequency domain sympathetic and parasympathetic indices. Among the HRV indices assessed, heart rate decreases with age and is lower in the night across all ages studied. The sympathetic index (SDNN) and the parasympathetic indices (RMSSD and pNN50) are not seen to change with age. Nevertheless, these indices were all higher during the day when compared to the night. Our findings appear to show that Rett patients are less adaptable to autonomic changes during the night. In the clinical setting, this might be more relevant for patients with severe psychopathology.

Vaccination Behavior Among Children With Developmental Delay and Their Siblings: A Cross-Sectional Study From India.

Objective: Despite scientific evidence to the contrary, parental concerns with respect to the association between vaccination and development of autism spectrum disorder persist. The objective of this study was to assess the vaccination uptake and its associated factors in siblings of children with developmental delay.Methods: This cross-sectional study was conducted from December 2017 to February 2018. The families of children with developmental delay, according to evaluation by a psychiatrist per ICD-10 criteria, were recruited from 3 child development centers. The data were collected using a semistructured questionnaire.Results: 189 families with children with developmental delay were recruited into the study. In total, these children had 114 typically developing elder siblings and 50 typically developing younger siblings. The proportions of overall complete vaccination among the children with developmental delay group and the younger sibling group were significantly lower than the older sibling group (P < .01). The proportions of MMR (mumps, measles, and rubella) vaccination among the children with developmental delay group and the younger sibling group were significantly lower than the older sibling group (P < .001).Conclusions: Findings from this study suggest that reduced vaccination uptake is a general trend in families of children with developmental delay. Such a significant decline in the vaccination rate in this group of children will make them vulnerable if outbreaks occur. Therefore, public health strategies targeted to improve vaccination rates in families of children with developmental delay are needed.

Early Social Experience and Digital-Media Exposure in Children with Autism Spectrum Disorder.

OBJECTIVE: To study the early social experience and digital media exposure in children with autism spectrum disorder (ASD) in comparison with typically developed children. METHODS: Details of digital-media exposure and early social experience in 65 children with ASD were compared with those in a control group of equal number of typically developed children, matched for age and gender. Prenatal and perinatal factors were also studied. The diagnosis of ASD was based on the International Clinical Epidemiology Network (INCLEN) diagnostic tool and Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) diagnostic criteria. Variables which were biologically relevant and has a P value of < 0.05 in the univariate analysis were analyzed by logistic regression to obtain the adjusted effect measures. RESULTS: Children with ASD were exposed to digital media at an earlier age and spent significantly more time with digital media and less time with their mothers, compared to typically developed children. Exposure to digital media before 21 mo was associated with risk of ASD and the risk increased when mothers spent less than 6.5 h per day with the baby. Family history of epilepsy and developmental delay, maternal stress during the antenatal period, and absence of exclusive breastfeeding during the first 6 mo were significantly more in children with ASD. CONCLUSION: There are significant differences in the early life social experience and digital-media exposure in children with ASD compared to typically developed counterparts. Given the reported rise in prevalence of ASD, these findings stress the need for further prospective studies to explore these potentially modifiable risk factors.

Exome sequencing reveals a novel splice site variant in HUWE1 gene in patients with suspected Say-Meyer syndrome.

Say-Meyer syndrome is a rare and clinically heterogeneous syndrome characterized by trigonocephaly, short stature, developmental delay and hypotelorism. Nine patients with this syndrome have been reported thus far although no causative gene has yet been identified. Here, we report two siblings with clinical phenotypes of Say-Meyer syndrome with moderate to severe intellectual disability and autism spectrum disorder. Cytogenetics and array-based comparative genomic hybridization did not reveal any chromosome abnormalities or copy number alterations. Exome sequencing of the patients revealed a novel X-linked recessive splice acceptor site variant c.145-2A > G in intron 5 of HUWE1 gene in both affected siblings. RT-PCR and sequencing revealed the use of an alternate cryptic splice acceptor site downstream, which led to deletion of six nucleotides resulting loss of two amino acids p.(Cys49-Glu50del) in HUWE1 protein. Deletion of these two amino acids, which are located in a highly conserved region, is predicted to be deleterious and quite likely to affect the function of HUWE1 protein. This is the first report of a potential candidate gene mutation for Say-Meyer syndrome, which was initially described four decades ago.

Immune aberrations in children with Autism Spectrum Disorder: a case-control study from a tertiary care neuropsychiatric hospital in India.

Multiple studies have identified the presence of peripheral immune aberrations in subjects with Autism Spectrum Disorder (ASD). However, comprehensive assessment of these peripheral immune aberrations, in the cellular and systemic compartments, in a single group of subjects with ASD is lacking. We assessed proportions of various subsets of immune cells in peripheral blood (T helper cells, T regulatory cells, B cells, monocytes, Natural Killer cells, dendritic cells) by multi-parametric flow cytometry in 50 children with ASD and compared it with thirty healthy controls matched for age, gender, socio-economic status and body mass index. There were no significant differences noted in the proportion of T regulatory cells, B cells, monocytes and Natural Killer cells, between ASD subjects and controls. On the contrary, the proportion of activated Th17 and myeloid dendritic cells were significantly higher in children with ASD. Based on these findings, group comparison of serum levels of Th17 cytokines (interleukin-6, interleukin-17A) was performed. Elevated serum levels of interleukin-6 and interleukin-17A in children with ASD corroborated our immunophenotyping findings. We did not find any significant differences among the pro-inflammatory (interleukin-1ß), Th1 (interferon-γ) and Th2 (interleukin-4) cytokines. This is the first evidence with concurrent findings from immunophenotyping and cytokine data demonstrating activation of the Th17 pathway in subjects with ASD. This finding assumes significance in the light of recent maternal immune activation mouse model study that has highlighted the role of Th17 pathway in the pathophysiology of ASD. Future longitudinal studies are needed to clarify the role of this dysregulated immune pathway in the development of ASD.

Neuropsychiatric Manifestations of Pediatric NMDA Receptor Autoimmune Encephalitis: A Case Series From a Tertiary Care Center in India.

OBJECTIVE: Although psychiatric manifestations are one of the most common presentations of pediatric N-methyl-D-aspartate receptor (NMDAR) encephalitis, there is a lack of studies that characterize psychiatric aspects of this disorder. This study was designed to address this gap. METHODS: Initial clinical presentations including psychiatric symptoms, treatment details, and outcome with respect to psychiatric symptoms were collected from medical case records of children aged less than 18 years with seropositive NMDAR encephalitis from a single tertiary care center (May 2010-November 2016). The Brief Psychiatric Rating Scale for Children (BPRS-C) was administered at the time of presentation and at follow-up. RESULTS: Clinical records from 16 girls and 5 boys of whom 12 were prepubertal (< 12 years) and 9 were postpubertal (≥ 12 years) were analyzed. All 21 children presented with psychiatric symptoms at initial presentation. In 10 children (47.6%), psychiatric symptom was the first symptom. Major psychiatric symptoms included inappropriate crying (most common, 66.7%, n = 14), social withdrawal (57.1%, n = 12), unprovoked anger outburst (47.6%, n = 10), unprovoked screaming behavior (38.1%, n = 8), and talking to self irrelevantly (42.9%, n = 9). In addition to psychiatric symptoms, at least 1 of the following was also seen in all children: speech disturbance (85.7%, n = 18), seizure (85.7%, n = 18), or movement disorder (76.2%, n = 16). Mood symptoms (85.7%, n = 18) were the most common psychopathology. A comorbid psychiatric diagnosis (ICD-10 criteria) was made in 11 children (52.4%); the most common was organic mood disorder (n = 6). The mean BPRS-C score at presentation in prepubertal children was higher than that of postpubertal children (21 vs 17). After immune modulation, clinical improvement was noted after a mean ± SD of 7.4 ± 4.8 months in all 20 children followed up. Three of the 4 children with residual psychiatric symptoms and persistent academic difficulties were prepubertal. CONCLUSIONS: Psychiatric manifestations that are usually mood related are quite common in pediatric NMDAR encephalitis. Prepubertal presentation of this disorder appears to be more severe and may lead to persistent psychiatric and cognitive symptoms.

Social experiential deprivation in autism spectrum disorders: A possible prognostic factor?

Autism spectrum disorders (ASD) are well known to be influenced by various environmental factors. Among these influencers, social experiential deprivation (SED) in infancy is one of them which is not well reported. We explored factors contributing to SED in 11 young children diagnosed to have ASD and compared them to 24 children without SED also having ASD. Intervention mainly addressing factors causing SED for 6 months demonstrated that children with SED had a better outcome at follow up. Could SED be a possible prognostic factor in children with ASD?