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  1. Bellato A, Sesso G, Milone A, Masi G, Cortese S
    J Am Acad Child Adolesc Psychiatry, 2024 Feb;63(2):216-230.
    PMID: 36841327 DOI: 10.1016/j.jaac.2023.01.017
    OBJECTIVE: To systematically investigate if there is a significant association between markers of autonomic functioning and emotional dysregulation (ED) in children and adolescents.

    METHOD: Based on a preregistered protocol (PROSPERO: CRD42021239635), PubMed, Web of Knowledge/Science, Ovid MEDLINE, Embase, and APA PsycInfo databases were searched until April 21, 2021, to identify empirical studies reporting indices of autonomic nervous system (ANS) functioning in youths meeting DSM (version III, IV, IV-TR, 5 or 5-TR) or International Classification of Diseases (ICD) (version 9 or 10) criteria for any psychopathological/neurodevelopmental condition and assessed for ED with a validated scale. Eligible outcomes included correlation coefficients between ED and ANS measures or differences in ANS measures between youths with and without ED. Study quality was assessed with the Appraisal tool for Cross-Sectional Studies (AXIS) and the Newcastle-Ottawa Scale (NOS) for cohort studies. Random-effects meta-analyses were used for data synthesis.

    RESULTS: There were 12 studies (1,016 participants) included in the descriptive review and 9 studies (567 participants) included in the meta-analyses. No evidence of a significant association between ED and altered cardiac or electrodermal functioning was found. However, exploratory meta-regressions suggested a possible association between reduced resting-state cardiac vagal control and increased ED.

    CONCLUSION: This study did not find evidence of an association between ED and autonomic dysfunction. However, preliminary evidence that reduced vagal control at rest might be a transdiagnostic marker of ED in young people was found. Additional studies comparing autonomic measures in youths with and without ED are needed and should also assess the effects of interventions for ED on ANS functioning.

    STUDY PREREGISTRATION INFORMATION: Systematic Review and Meta-Analysis: Is Autonomic Nervous System Functioning Atypical in Children and Adolescents With Emotional Dysregulation? https://www.crd.york.ac.uk/prospero/; CRD42021239635.

    Matched MeSH terms: Neurodevelopmental Disorders*
  2. Gyllenberg D, Bastola K, Wan Mohd Yunus WMA, Mishina K, Liukko E, Kääriälä A, et al.
    PLoS Med, 2023 Feb;20(2):e1004072.
    PMID: 36848384 DOI: 10.1371/journal.pmed.1004072
    BACKGROUND: Coronavirus Disease 2019 (COVID-19) restrictions decreased the use of specialist psychiatric services for children and adolescents in spring 2020. However, little is known about the pattern once restrictions eased. We compared new psychiatric diagnoses by specialist services during pandemic and pre-pandemic periods.

    METHODS AND FINDINGS: This national register study focused on all Finnish residents aged 0 to 17 years from January 2017 to September 2021 (approximately 1 million a year). The outcomes were new monthly diagnoses for psychiatric or neurodevelopmental disorders in specialist services. These were analyzed by sex, age, home location, and diagnostic groups. The numbers of new diagnoses from March 2020 were compared to predictive models based on previous years. The predicted and observed levels in March to May 2020 showed no significant differences, but the overall difference was 18.5% (95% confidence interval 12.0 to 25.9) higher than predicted in June 2020 to September 2021, with 3,821 more patients diagnosed than anticipated. During this period, the largest increases were among females (33.4%, 23.4 to 45.2), adolescents (34.4%, 25.0 to 45.3), and those living in areas with the highest COVID-19 morbidity (29.9%, 21.2 to 39.8). The largest increases by diagnostic groups were found for eating disorders (27.4%, 8.0 to 55.3), depression and anxiety (21.0%, 12.1 to 51.9), and neurodevelopmental disorders (9.6%, 3.0 to 17.0), but psychotic and bipolar disorders and conduct and oppositional disorders showed no significant differences and self-harm (-28.6, -41.5 to -8.2) and substance use disorders (-15.5, -26.4 to -0.7) decreased in this period. The main limitation is that data from specialist services do not allow to draw conclusions about those not seeking help.

    CONCLUSIONS: Following the first pandemic phase, new psychiatric diagnoses in children and adolescents increased by nearly a fifth in Finnish specialist services. Possible explanations to our findings include changes in help-seeking, referrals and psychiatric problems, and delayed service access.

    Matched MeSH terms: Neurodevelopmental Disorders*
  3. Berry C, Othman E, Tan JC, Gee B, Byrne RE, Hodgekins J, et al.
    BMC Psychiatry, 2019 06 20;19(1):188.
    PMID: 31221136 DOI: 10.1186/s12888-019-2164-x
    BACKGROUND: A social recovery approach to youth mental health focuses on increasing the time spent in valuable and meaningful structured activities, with a view to preventing enduring mental health problems and social disability. In Malaysia, access to mental health care is particularly limited and little research has focused on identifying young people at risk of serious socially disabling mental health problems such as psychosis. We provide preliminary evidence for the feasibility and acceptability of core social recovery assessment tools in a Malaysian context, comparing the experiential process of engaging young Malaysian participants in social recovery assessments with prior accounts from a UK sample.

    METHODS: Nine vulnerable young people from low-income backgrounds were recruited from a non-government social enterprise and partner organisations in Peninsular Malaysia. Participants completed a battery of social recovery assessment tools (including time use, unusual experiences, self-schematic beliefs and values). Time for completion and completion rates were used as indices of feasibility. Acceptability was examined using qualitative interviews in which participants were asked to reflect on the experience of completing the assessment tools. Following a deductive approach, the themes were examined for fit with previous UK qualitative accounts of social recovery assessments.

    RESULTS: Feasibility was indicated by relatively efficient completion time and high completion rates. Qualitative interviews highlighted the perceived benefits of social recovery assessments, such as providing psychoeducation, aiding in self-reflection and stimulating goal setting, in line with findings from UK youth samples.

    CONCLUSIONS: We provide preliminary evidence for the feasibility and acceptability of social recovery assessment tools in a low-resource context, comparing the experiential process of engaging young Malaysian participants in social recovery assessments with prior accounts from a UK sample. We also suggest that respondents may derive some personal and psychoeducational benefits from participating in assessments (e.g. of their time use and mental health) within a social recovery framework.

    Matched MeSH terms: Neurodevelopmental Disorders/economics*; Neurodevelopmental Disorders/ethnology; Neurodevelopmental Disorders/therapy*
  4. Nakashima M, Tohyama J, Nakagawa E, Watanabe Y, Siew CG, Kwong CS, et al.
    J Hum Genet, 2019 Apr;64(4):313-322.
    PMID: 30655572 DOI: 10.1038/s10038-018-0559-z
    Casein kinase 2 (CK2) is a serine threonine kinase ubiquitously expressed in eukaryotic cells and involved in various cellular processes. In recent studies, de novo variants in CSNK2A1 and CSNK2B, which encode the subunits of CK2, have been identified in individuals with intellectual disability syndrome. In this study, we describe four patients with neurodevelopmental disorders possessing de novo variants in CSNK2A1 or CSNK2B. Using whole-exome sequencing, we detected two de novo variants in CSNK2A1 in two unrelated Japanese patients, a novel variant c.571C>T, p.(Arg191*) and a recurrent variant c.593A>G, p.(Lys198Arg), and two novel de novo variants in CSNK2B in Japanese and Malaysian patients, c.494A>G, p.(His165Arg) and c.533_534insGT, p.(Pro179Tyrfs*49), respectively. All four patients showed mild to profound intellectual disabilities, developmental delays, and various types of seizures. This and previous studies have found a total of 20 CSNK2A1 variants in 28 individuals with syndromic intellectual disability. The hotspot variant c.593A>G, p.(Lys198Arg) was found in eight of 28 patients. Meanwhile, only five CSNK2B variants were identified in five individuals with neurodevelopmental disorders. We reviewed the previous literature to verify the phenotypic spectrum of CSNK2A1- and CSNK2B-related syndromes.
    Matched MeSH terms: Neurodevelopmental Disorders/genetics; Neurodevelopmental Disorders/physiopathology
  5. Tew SP, Ahmad Fauzi A
    Child Care Health Dev, 2020 09;46(5):585-590.
    PMID: 32410244 DOI: 10.1111/cch.12773
    BACKGROUND: Neurodevelopmental disabilities are amongst the main conditions encountered in our paediatric rehabilitation centre. To identify the necessary actions to achieve family-centred care in the tertiary healthcare division, we explored the perceptions of parents on the paediatric rehabilitation services received by their children with neurodevelopmental disabilities.

    METHOD: A cross-sectional study involving 200 parents of children with neurodevelopmental disabilities aged 1-18 years was carried out. The Malay version of the Measure of Process of Care (MPOC-20) questionnaire was used to measure the perceptions of parents on the services. Descriptive statistical analysis was done to describe the mean score of each MPOC-20 scale. Univariate and bivariate analyses were used to examine the associations between the characteristics of parents and children as well as the sociodemographic and environmental factors with the MPOC-20 scales.

    RESULTS: The mean score of the MPOC-20 scales ranged from 4.50 to 5.65 (SD 0.93-1.51). Amongst the MPOC-20 scales, parents ranked enabling, having good partnership and being comprehensive (EP) the highest, whereas the provision of specific information (PS) received the lowest score. Amongst all the MPOC-20 scales, significant differences were shown in parent's employment, between children's age groups and between ethnic groups.

    CONCLUSIONS: The Malay MPOC-20 is a validated tool that can be used in evaluation of services among the Malay-speaking community, and therefore, it is recommended for our clinical use to improve family-centred practice in paediatric rehabilitation.

    Matched MeSH terms: Neurodevelopmental Disorders/rehabilitation*
  6. Thamrin V, Saugstad OD, Tarnow-Mordi W, Wang YA, Lui K, Wright IM, et al.
    J Pediatr, 2018 10;201:55-61.e1.
    PMID: 30251639 DOI: 10.1016/j.jpeds.2018.05.053
    OBJECTIVE: To determine rates of death or neurodevelopmental impairment (NDI) at 2 years corrected age (primary outcome) in children <32 weeks' gestation randomized to initial resuscitation with a fraction of inspired oxygen (FiO2) value of 0.21 or 1.0.

    STUDY DESIGN: Blinded assessments were conducted at 2-3 years corrected age with the Bayley Scales of Infant and Toddler Development, Third Edition or the Ages and Stages Questionnaire by intention to treat.

    RESULTS: Of the 290 children enrolled, 40 could not be contacted and 10 failed to attend appointments. Among the 240 children for whom outcomes at age 2 years were available, 1 child had a lethal congenital anomaly, 1 child had consent for follow-up withdrawn, and 23 children died. The primary outcome, which was available in 238 (82%) of those randomized, occurred in 47 of the 117 (40%) children assigned to initial FiO2 0.21 and in 38 of the 121 (31%) assigned to initial FiO2 1.0 (OR, 1.47; 95% CI, 0.86-2.5; P = .16). No difference in NDI was found in 215 survivors randomized to FiO2 0.21 vs 1.0 (OR, 1.26; 95% CI, 0.70-2.28; P = .11). In post hoc exploratory analyses in the whole cohort, children with a 5-minute blood oxygen saturation (SpO2) <80% were more likely to die or to have NDI (OR, 1.85; 95% CI, 1.07-3.2; P = .03).

    CONCLUSIONS: Initial resuscitation of infants <32 weeks' gestation with initial FiO2 0.21 had no significant effect on death or NDI compared with initial FiO2 1.0. Further evaluation of optimum initial FiO2, including SpO2 targeting, in a large randomized controlled trial is needed.

    TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Network Registry ACTRN 12610001059055 and the National Malaysian Research Registry NMRR-07-685-957.

    Matched MeSH terms: Neurodevelopmental Disorders/epidemiology*
  7. Kvestad I, Hysing M, Shrestha M, Ulak M, Thorne-Lyman AL, Henjum S, et al.
    Am J Clin Nutr, 2017 05;105(5):1122-1131.
    PMID: 28330909 DOI: 10.3945/ajcn.116.144931
    Background: Poor vitamin B-12 (cobalamin) status is widespread in South Asia. Insufficient vitamin B-12 status has been linked to poor neurodevelopment in young children.Objective: We measured the associations between vitamin B-12 status in infancy (2-12 mo) and the development and cognitive functioning in Nepalese children 5 y later.Design: Vitamin B-12 status was assessed in infancy with the use of plasma cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA). At 5 y of age, we measured development with the use of the Ages and Stages Questionnaire, 3rd edition (ASQ-3), and cognitive functioning by using the Developmental Neuropsychological Assessment, 2nd edition (NEPSY II), in 320 children. In regression models, we estimated the associations between vitamin B-12 status, including a combined indicator of vitamin B-12 status (3cB12) and scores on the ASQ-3 and NEPSY II subtests.Results: All markers of vitamin B-12 status with the exception of plasma cobalamin were significantly associated with the total ASQ-3 scores in the multiple regression models. A 1-unit increase in the 3cB12 score was associated with an increase in the total ASQ-3 score of 4.88 (95% CI: 2.09, 7.68; P = 0.001). Increases in both plasma tHcy and MMA (indicating poorer status) were associated with a decrease in scores on the NEPSY II affect recognition and geometric puzzle subtests. Each unit increment in 3cB12 scores was associated with increases of 0.82 (95% CI: 0.49, 1.14; P < 0.0005), 0.59 (95% CI: 0.10, 1.09; P = 0.020), and 0.24 (95% CI: 0.02, 0.47; P = 0.035) in the affect recognition, geometric puzzle, and block construction scores, respectively.Conclusions: Vitamin B-12 status in infancy is associated with development and performance on social perception tasks and visuospatial abilities at 5 y of age. The long-term effects of poor vitamin B-12 status in infancy need further investigation in randomized controlled trials.
    Matched MeSH terms: Neurodevelopmental Disorders/blood; Neurodevelopmental Disorders/etiology*
  8. den Hoed J, de Boer E, Voisin N, Dingemans AJM, Guex N, Wiel L, et al.
    Am J Hum Genet, 2021 02 04;108(2):346-356.
    PMID: 33513338 DOI: 10.1016/j.ajhg.2021.01.007
    Whereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying SATB1 variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression, and a severe phenotype. In contrast, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability.
    Matched MeSH terms: Neurodevelopmental Disorders/genetics*
  9. Juvale IIA, Che Has AT
    J Mol Neurosci, 2021 Jul;71(7):1338-1355.
    PMID: 33774758 DOI: 10.1007/s12031-021-01825-7
    Neurodevelopmental disorders are defined as a set of abnormal brain developmental conditions marked by the early childhood onset of cognitive, behavioral, and functional deficits leading to memory and learning problems, emotional instability, and impulsivity. Autism spectrum disorder, attention-deficit/hyperactivity disorder, Tourette syndrome, fragile X syndrome, and Down's syndrome are a few known examples of neurodevelopmental disorders. Although they are relatively common in both developed and developing countries, very little is currently known about their underlying molecular mechanisms. Both genetic and environmental factors are known to increase the risk of neurodevelopmental disorders. Current diagnostic and screening tests for neurodevelopmental disorders are not reliable; hence, individuals with neurodevelopmental disorders are often diagnosed in the later stages. This negatively affects their prognosis and quality of life, prompting the need for a better diagnostic biomarker. Recent studies on microRNAs and their altered regulation in diseases have shed some light on the possible role they could play in the development of the central nervous system. This review attempts to elucidate our current understanding of the role that microRNAs play in neurodevelopmental disorders with the hope of utilizing them as potential biomarkers in the future.
    Matched MeSH terms: Neurodevelopmental Disorders/diagnosis*; Neurodevelopmental Disorders/genetics
  10. Yap MS, Nathan KR, Yeo Y, Lim LW, Poh CL, Richards M, et al.
    Stem Cells Int, 2015;2015:105172.
    PMID: 26089911 DOI: 10.1155/2015/105172
    Human pluripotent stem cells (hPSCs) derived from either blastocyst stage embryos (hESCs) or reprogrammed somatic cells (iPSCs) can provide an abundant source of human neuronal lineages that were previously sourced from human cadavers, abortuses, and discarded surgical waste. In addition to the well-known potential therapeutic application of these cells in regenerative medicine, these are also various promising nontherapeutic applications in toxicological and pharmacological screening of neuroactive compounds, as well as for in vitro modeling of neurodegenerative and neurodevelopmental disorders. Compared to alternative research models based on laboratory animals and immortalized cancer-derived human neural cell lines, neuronal cells differentiated from hPSCs possess the advantages of species specificity together with genetic and physiological normality, which could more closely recapitulate in vivo conditions within the human central nervous system. This review critically examines the various potential nontherapeutic applications of hPSC-derived neuronal lineages and gives a brief overview of differentiation protocols utilized to generate these cells from hESCs and iPSCs.
    Matched MeSH terms: Neurodevelopmental Disorders
  11. Martadza M, Saedon UI, Darus N, Badli TST, Ghazalan SA, Yunus WMAWM
    Malays J Med Sci, 2019 Nov;26(6):111-119.
    PMID: 31908592 MyJurnal DOI: 10.21315/mjms2019.26.6.11
    Background: This descriptive study identifies the demographic characteristics and patterns of referral to clinical psychology services, which include types of diagnosis, types of referral and source of referrals in child, adolescent, adult and geriatric cases in Malaysia.

    Methods: We utilised 2,179 referrals between January and December 2015 from six general hospitals and three mental health institutions that provide clinical psychology services.

    Results: The percentage of male referrals (60.3%) is higher than that of female referrals (39.7%). Adult cases had the highest percentage of referrals (48.2%). Children (48.8%) and adolescent (28.1%) cases were mainly referred for psychological assessment. Meanwhile, adult cases (74.8%) were mainly referred for psychological intervention. Neurodevelopmental disorders was the diagnosis with the highest percentage of referrals recorded (41.4%), followed by depressive disorders (13.3%) and anxiety disorders (12.7%), and the combination of other disorders. Psychiatrists provided the highest number of referrals (82.2%), which is unsurprising as both fields are closely related.

    Conclusion: Clinical psychology services within the Ministry of Health (MOH) Malaysia play an important role in mental health care.

    Matched MeSH terms: Neurodevelopmental Disorders
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