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Pharmacology, Biochemistry, and Behavior Sep 2023Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications.... (Review)
Review
Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications. These phyto-cannabinoids have multiple biological targets, including the body's endocannabinoid system. There is growing scientific interest in the use of CBD, a non-intoxicating compound, to ameliorate symptoms associated with neurodevelopmental disorders. However, its suitability as a pharmaceutical intervention has not been reliably established in these clinical populations. This systematic review examines the nine published randomised controlled trials (RCTs) that have probed the safety and efficacy of CBD in individuals diagnosed with attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability, Tourette Syndrome, and complex motor disorders. Studies were identified systematically through searching four databases: Medline, CINAHL complete, PsycINFO, and EMBASE. Inclusion criteria were randomised controlled trials involving CBD and participants with neurodevelopmental disorders. No publication year or language restrictions were applied. Relevant data were extracted from the identified list of eligible articles. After extraction, data were cross-checked between the authors to ensure consistency. Several trials indicate potential efficacy, although this possibility is currently too inconsistent across RCTs to confidently guide clinical usage. Study characteristics, treatment properties, and outcomes varied greatly across the included trials. The material lack of comparable RCTs leaves CBD's suitability as a pharmacological treatment for neurodevelopmental disorders largely undetermined. A stronger evidence base is urgently required to establish safety and efficacy profiles and guide the ever-expanding clinical uptake of cannabis-derived compounds in neurodevelopmental disorders. Prospero registration number: CRD42021267839.
Topics: Humans; Cannabidiol; Cannabinoids; Cannabis; Hallucinogens; Attention Deficit Disorder with Hyperactivity; Dronabinol; Randomized Controlled Trials as Topic
PubMed: 37543051
DOI: 10.1016/j.pbb.2023.173607 -
The Journal of Clinical Endocrinology... Aug 2023Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by...
CONTEXT
Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by pathogenic variants in TBCE and FAM111A, respectively. Clinically the phenotypes are difficult to distinguish.
OBJECTIVE
The objective was to determine and expand the phenotypic spectrum of KCS1 and KCS2 in order to anticipate complications that may arise in these disorders.
METHODS
We clinically and genetically analyzed 10 KCS2 patients from 7 families. Because we found unusual phenotypes in our cohort, we performed a systematic review of genetically confirmed KCS cases using PubMed and Scopus. Evaluation by 3 researchers led to the inclusion of 26 papers for KCS1 and 16 for KCS2, totaling 205 patients. Data were extracted following the Cochrane guidelines and assessed by 2 independent researchers.
RESULTS
Several patients in our KCS2 cohort presented with intellectual disability (3/10) and chronic kidney disease (6/10), which are not considered common findings in KCS2. Systematic review of all reported KCS cases showed that the phenotypes of KCS1 and KCS2 overlap for postnatal growth retardation (KCS1: 52/52, KCS2: 23/23), low parathyroid hormone levels (121/121, 16/20), electrolyte disturbances (139/139, 24/27), dental abnormalities (47/50, 15/16), ocular abnormalities (57/60, 22/23), and seizures/spasms (103/115, 13/16). Symptoms more prevalent in KCS1 included intellectual disability (74/80, 5/24), whereas in KCS2 bone cortical thickening (1/18, 16/20) and medullary stenosis (7/46, 27/28) were more common.
CONCLUSION
Our case series established chronic kidney disease as a new feature of KCS2. In the literature, we found substantial overlap in the phenotypic spectra of KCS1 and KCS2, but identified intellectual disability and the abnormal bone phenotype as the most distinguishing features.
Topics: Humans; Intellectual Disability; Hyperostosis, Cortical, Congenital; Phenotype; Electrolytes; Hypoparathyroidism
PubMed: 36916904
DOI: 10.1210/clinem/dgad147 -
Neuroscience and Biobehavioral Reviews Oct 2023Abnormal gestational weight gain (GWG) has been increasing globally, up to 47% of all pregnancies. Multiple studies have focused on the association between GWG and... (Meta-Analysis)
Meta-Analysis Review
Abnormal gestational weight gain (GWG) has been increasing globally, up to 47% of all pregnancies. Multiple studies have focused on the association between GWG and adverse neurodevelopmental outcomes in the offspring, however with inconsistent results. We performed a systematic review and meta-analysis to evaluate associations between excessive or insufficient GWG and offspring's neurodevelopmental outcomes. Meta-analysis of these 23 studies using a random-effects model revealed associations between excessive GWG and neurodevelopmental disorders (ASD & ID & ADHD together: OR=1.12 [95% CI 1.06-1.19]), ASD (OR=1.18 [95% CI 1.08-1.29]), ADHD (OR=1.08 [95% CI 1.02-1.14]), ASD with ID (OR=1.15 [95% CI 1.01-1.32]), and ASD without ID (OR=1.12 [95% CI 1.06-1.19]). Insufficient GWG was associated with higher risk for ID (OR=1.14 [95% CI 1.03-1.26]). These results emphasize the significant impact, though of small effect size, of GWG across multiple neurodevelopmental disorders. It is important to note that these results do not establish causality. Other factors such as genetic factors, gene-environment interactions may confound the relationship between GWG and neurodevelopmental outcomes. To better understand the role of GWG in neurodevelopmental disorders, future studies should consider using genetically sensitive designs that can account for these potential confounders.
Topics: Pregnancy; Female; Humans; Gestational Weight Gain; Weight Gain; Neurodevelopmental Disorders; Body Mass Index
PubMed: 37573899
DOI: 10.1016/j.neubiorev.2023.105360 -
Journal of Clinical Medicine Sep 2023Long-term medication with valproic acid has been associated with acute pancreatitis. The purpose of this report is to gain insight into the features of this... (Review)
Review
Long-term medication with valproic acid has been associated with acute pancreatitis. The purpose of this report is to gain insight into the features of this pancreatitis. A preregistered literature search (CRD42023438294) was performed on the National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar. Patients with alcohol abuse disorder, gallstone disease, hypertriglyceridemia or hypercalcemia, patients with acute valproic acid intoxication, and patients with a pre-existing pancreatitis were excluded. For the final analysis, we retained 73 reports published between 1979 and 2023, which described 125 subjects (83 children and 42 adults predominantly affected by an epilepsy) with an acute pancreatitis related to valproic acid. The diagnosis was made 11 (3.0-24) months (median and interquartile range) after starting valproic acid. One hundred and five cases (84%) recovered and twenty (16%) died. Sex, age, dosage or circulating level of valproic acid, latency time, prevalence of intellectual disability, and antiepileptic co-medication were similar in cases with and without a lethal outcome. Nineteen subjects were rechallenged with valproic acid after recovery: sixteen (84%) cases developed a further episode of pancreatitis. In conclusion, pancreatitis associated with valproic acid presents at any time during treatment and has a high fatality rate.
PubMed: 37762984
DOI: 10.3390/jcm12186044 -
Sleep Medicine Reviews Oct 2023The purpose of this systematic review and meta-analysis is to delineate the concordance of objective and subjective measures of sleep in children with neurodevelopmental... (Review)
Review
The purpose of this systematic review and meta-analysis is to delineate the concordance of objective and subjective measures of sleep in children with neurodevelopmental conditions (NDCs). A systematic literature search identified 31 studies that compare objective and subjective estimates of sleep parameters in autism, ADHD or rare genetic syndromes associated with intellectual disability. The meta-analyses revealed smaller mean differences and larger correlations indicative of greater concordance for parameters associated with sleep scheduling compared to parameters associated with sleep duration and night awakenings. Relative to objective measures, subjective measures produced: 1) greater estimates of total sleep time, sleep efficiency and time in bed; and 2) lower estimates of wake after sleep onset and number of night awakenings. Subgroup analyses also revealed differences in concordance between measurement comparison types (e.g., stronger correlations between actigraphy and sleep diaries, compared to actigraphy and questionnaires) and NDC diagnostic groups. The results predominantly replicate concordance trends observed in typically-developing samples, although some NDC-specific patterns of concordance were identified. This indicates that objective and subjective sleep measures retain broadly similar properties across populations, although researchers and clinicians should be cautious of the impact of NDC-related characteristics on sleep parameter estimates. These findings should inform sleep assessment design and the interpretation of sleep parameter estimates in NDCs, increasing the rigour of sleep parameter description across research and clinical settings.
PubMed: 37422998
DOI: 10.1016/j.smrv.2023.101814 -
Molecular Autism Jul 2023Septo-optic dysplasia (SOD) is a rare condition diagnosed in children with two or more of the following: hypopituitarism, midline brain abnormalities, and optic nerve... (Review)
Review
BACKGROUND
Septo-optic dysplasia (SOD) is a rare condition diagnosed in children with two or more of the following: hypopituitarism, midline brain abnormalities, and optic nerve hypoplasia. Children with SOD experience varied visual impairment and endocrine dysfunction. Autistic-like behaviours have been reported; however, their nature and prevalence remain to be fully understood. The present systematic review aimed to explore the type and prevalence of neurodevelopmental impairments in children with SOD spectrum conditions.
METHODS
The search was conducted in PubMed, EMBASE, and PsycInfo. Hand-searching reference lists of included studies was conducted. All peer-reviewed, observational studies assessing behavioural and cognitive impairments or autism spectrum disorder (ASD) symptoms in children (< 18 years) with SOD, optic nerve hypoplasia, and SOD-plus were included. Studies were excluded if they did not report standardised measures of neurodevelopmental impairments or ASD outcomes.
RESULTS
From 2132 screened articles, 20 articles reporting data from a total of 479 children were included in prevalence estimates. Of 14 studies assessing cognitive-developmental outcomes, 175 of 336 (52%) children presented with intellectual disability or developmental delay. A diagnosis of ASD or clinical level of symptoms was observed in 65 of 187 (35%) children across five studies. Only five studies assessed for dysfunction across behavioural, emotional, or social domains and reported impairments in 88 of 184 (48%) of children assessed.
LIMITATIONS
Importantly, high heterogeneity among the samples in relation to their neuroanatomical, endocrine, and optic nerve involvement meant that it was not possible to statistically assess the relative contribution of these confounding factors to the specific neurodevelopmental phenotype. This was further limited by the variation in study designs and behavioural assessments used across the included studies, which may have increased the risk of information bias.
CONCLUSIONS
This systematic review suggests that the prevalence of neurodevelopmental impairments in children within the SOD spectrum may be high. Clinicians should therefore consider including formal assessments of ASD symptoms and neurodevelopmental impairments alongside routine care. There is, additionally, a need for further research to define and validate a standardised battery of tools that accurately identify neurodevelopmental impairments in SOD spectrum conditions, and for research to identify the likely causal mechanisms.
Topics: Humans; Septo-Optic Dysplasia; Autism Spectrum Disorder; Optic Nerve Hypoplasia; Hypopituitarism; Autistic Disorder
PubMed: 37491272
DOI: 10.1186/s13229-023-00559-0 -
European Child & Adolescent Psychiatry Feb 2024A better understanding of the endocannabinoid system and a relaxation in regulatory control of cannabis globally has increased interest in the medicinal use of... (Review)
Review
A better understanding of the endocannabinoid system and a relaxation in regulatory control of cannabis globally has increased interest in the medicinal use of cannabinoid-based products (CBP). We provide a systematic review of the rationale and current clinical trial evidence for CBP in the treatment of neuropsychiatric and neurodevelopmental disorders in children and adolescents. A systematic search of MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Trials was performed to identify articles published after 1980 about CBP for medical purposes in individuals aged 18 years or younger with selected neuropsychiatric or neurodevelopmental conditions. Risk of bias and quality of evidence was assessed for each article. Of 4466 articles screened, 18 were eligible for inclusion, addressing eight conditions (anxiety disorders (n = 1); autism spectrum disorder (n = 5); foetal alcohol spectrum disorder (n = 1); fragile X syndrome (n = 2); intellectual disability (n = 1); mood disorders (n = 2); post-traumatic stress disorder (n = 3); and Tourette syndrome (n = 3)). Only one randomised controlled trial (RCT) was identified. The remaining seventeen articles included one open-label trial, three uncontrolled before-and-after trials, two case series and 11 case reports, thus the risk of bias was high. Despite growing community and scientific interest, our systematic review identified limited and generally poor-quality evidence for the efficacy of CBP in neuropsychiatric and neurodevelopmental disorders in children and adolescents. Large rigorous RCTs are required to inform clinical care. In the meantime, clinicians must balance patient expectations with the limited evidence available.
Topics: Child; Humans; Adolescent; Cannabinoids; Anxiety Disorders; Stress Disorders, Post-Traumatic; Tourette Syndrome
PubMed: 36864363
DOI: 10.1007/s00787-023-02169-w -
Indian Journal of Psychiatry Nov 2023After the National Mental Health Survey in 2016, multiple individual studies showed inconsistencies in the prevalence rates of psychiatric disorders in India. We... (Review)
Review
BACKGROUND
After the National Mental Health Survey in 2016, multiple individual studies showed inconsistencies in the prevalence rates of psychiatric disorders in India. We performed a meta-analysis to estimate an up-to-date pooled estimate of the prevalence of depression, alcohol use disorder (AUD), anxiety disorder (AD), intellectual disability, suicidal attempt/death, autism, and bipolar disorder (BD) in India.
MATERIALS AND METHODS
We performed a systematic bibliographic search in Pub Med, Global Health Data Exchange (GHDx), and Google Scholar, along with a manual search for peer-reviewed epidemiological studies reporting the prevalence of depression, AUD, AD, MR, suicidal attempt/death, autism, and BD in India from January 1980 till March 2022. Adopting a random-effects model, we performed the meta-analysis using "MetaXL" software.
RESULTS
A total of 79 studies were included: depression ( = 28), AUD ( = 14), AD ( = 12), intellectual disability ( = 8), suicidal attempt/death ( = 7), autism ( = 6) and BD ( = 4). The pooled prevalence of depression and AUD was 12.4% (95% CI 9.4-15.9) ( < 0.001, I = 100%) and 21.5% (95% CI 14.1-30.0) ( < 0.001, I = 100%), respectively. AD, intellectual disability and suicidal attempt/death showed a prevalence of 11.6% (95% CI 8.1-15.7) ( < 0.001, I = 99%), 1% (95% CI 0.5-1.6) ( < 0.001, I = 98%) and 0.5% (95% CI 0.3-0.8) ( < 0.001, I = 100%), respectively. The meta-analysis in autism and BD showed pooled prevalence of 0.3% (95% CI 0.1-0.6) ( < 0.001, I = 96%) and 0.3% (95% CI 0.2-0.4) ( < 0.001, I = 78%), respectively. Subgroup analysis showed an increased prevalence of AD in the urban [24.3% (95% CI 3.7-52.9)] and younger [16.7% (95% CI 5.1-32.7)] population. The prevalence of depression and AD increased during the last two decades on decadal prevalence analysis.
DISCUSSION
The findings could be used for appropriate policy measures and guiding subsequent national mental health surveys.
PubMed: 38249146
DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_539_22 -
Epidemiology and Psychiatric Sciences Jul 2023This study aimed to summarize the evidence on sleep alterations in medication-naïve children and adolescents with autism spectrum disorder (ASD). (Meta-Analysis)
Meta-Analysis
AIMS
This study aimed to summarize the evidence on sleep alterations in medication-naïve children and adolescents with autism spectrum disorder (ASD).
METHODS
We systematically searched PubMed/Medline, Embase and Web of Science databases from inception through March 22, 2021. This study was registered with PROSPERO (CRD42021243881). Any observational study was included that enrolled medication-naïve children and adolescents with ASD and compared objective (actigraphy and polysomnography) or subjective sleep parameters with typically developing (TD) counterparts. We extracted relevant data such as the study design and outcome measures. The methodological quality was assessed through the Newcastle-Ottawa Scale (NOS). A meta-analysis was carried out using the random-effects model by pooling effect sizes as Hedges' . To assess publication bias, Egger's test and -curve analysis were done. A priori planned meta-regression and subgroup analysis were also performed to identify potential moderators.
RESULTS
Out of 4277 retrieved references, 16 studies were eligible with 981 ASD patients and 1220 TD individuals. The analysis of objective measures showed that medication-naïve ASD patients had significantly longer sleep latency (Hedges' 0.59; 95% confidence interval [95% CI] 0.26 to 0.92), reduced sleep efficiency (Hedges' -0.58; 95% CI -0.87 to -0.28), time in bed (Hedges' -0.64; 95% CI -1.02 to -0.26) and total sleep time (Hedges' -0.64; 95% CI -1.01 to -0.27). The analysis of subjective measures showed that they had more problems in daytime sleepiness (Hedges' 0.48; 95% CI 0.26 to 0.71), sleep latency (Hedges' 1.15; 95% CI 0.72 to 1.58), initiating and maintaining sleep (Hedges' 0.86; 95% CI 0.39 to 1.33) and sleep hyperhidrosis (Hedges' 0.48; 95% CI 0.29 to 0.66). Potential publication bias was detected for sleep latency, sleep period time and total sleep time measured by polysomnography. Some sleep alterations were moderated by age, sex and concurrent intellectual disability. The median NOS score was 8 (interquartile range 7.25-8.75).
CONCLUSION
We found that medication-naïve children and adolescents with ASD presented significantly more subjective and objective sleep alterations compared to TD and identified possible moderators of these differences. Future research requires an analysis of how these sleep alterations are linked to core symptom severity and comorbid behavioural problems, which would provide an integrated therapeutic intervention for ASD. However, our results should be interpreted in light of the potential publication bias.
Topics: Humans; Child; Adolescent; Autism Spectrum Disorder; Sleep; Comorbidity; Outcome Assessment, Health Care; Observational Studies as Topic
PubMed: 37469173
DOI: 10.1017/S2045796023000574 -
Frontiers in Pediatrics 2023To study the worldwide prevalence and associated factors of epilepsy in children and adolescents with Cerebral Palsy (CP) and to analyze the differences between various... (Review)
Review
OBJECTIVE
To study the worldwide prevalence and associated factors of epilepsy in children and adolescents with Cerebral Palsy (CP) and to analyze the differences between various subgroups.
METHOD
We identified all potential studies on the prevalence of epilepsy in children and adolescents with CP from PubMed, Web of Science, and Embase. The search time was from the establishment of the database to November 2022. Randomized effects meta-analysis models were used to calculate the prevalence of epilepsy in CP. Subgroup analysis and meta-regression were utilized to further explore heterogeneity between articles and prevalence disparities between subgroups. The funnel plot and Egger's test were used to investigate potential publication bias.
RESULTS
Seventy-two articles, comprising 53,969 children and adolescents with CP, were included in this study. The results indicated a total epilepsy prevalence of 38.0% (95% CI: 34.8%-41.2%) in CP. The prevalence of epilepsy was 46.4% (95% CI: 41.4%-51.5%) in clinical sample-based studies and 31.6% (95% CI: 28.7%-34.5%) in population-based studies. Meta-regression demonstrated that the sample source, neonatal seizure, family history of epilepsy, EEG or cranial imaging abnormalities, intellectual/cognitive impairment, and topographical types of CP were heterogeneous contributors to the epilepsy prevalence in CP.
CONCLUSION
Approximately one-third of children and adolescents with CP have epilepsy, and the sample source can significantly impact the total prevalence of epilepsy. Neonatal seizures, family history of epilepsy, EEG abnormalities, cranial imaging abnormalities, severe intellectual disability, and quadriplegia may be contributing factors to epilepsy comorbid in CP. Further study is required to verify the strength of these associations with epilepsy. This study aids in identifying the clinical characteristics of young people with CP at risk of developing epilepsy, which may assist clinicians in the early prevention and diagnosis of epilepsy within this population. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367766, identifier CRD42022367766.
PubMed: 37576141
DOI: 10.3389/fped.2023.1189648