Childhood Neuropsychiatric Disorders Research Articles

Prenatal opioid exposure and subsequent risk of neuropsychiatric disorders in children: nationwide birth cohort study in South Korea

SummaryObjectiveTo investigate the potential association between prenatal opioid exposure and the risk of neuropsychiatric disorders in children.DesignNationwide birth cohort study.SettingFrom 1 January 2009 to 31 December 2020, birth cohort data...

Neuropsychiatric Aspects of Sotos Syndrome: Explorative Review Building Multidisciplinary Bridges in Clinical Practice.

Background: Sotos syndrome is a genetic disorder caused by NSD1 gene (nuclear receptor binding SET domain containing protein 1) variants and characterized by overgrowth, macrocephaly, learning disabilities, and co-occurring neuropsychiatric symptoms. Methods: Literature sources published in 2002-2023 were selected and analyzed from PubMed and Google Scholar databases. Results: Neuropsychiatric symptoms are observed among children and adolescents with Sotos syndrome. The majority have intellectual disabilities or borderline intellect. Verbal IQ is higher than performance IQ. Individuals display difficulties in expressing language. Aggression is reported by parents. Children express autistic behavior, ADHD, anxiety based on phobias, and early bedtime-wake times. Conclusions: Sotos syndrome is associated with neuropsychiatric disorders in children. Slow intellectual and language development, aggressive outbursts, anxiety, autism spectrum disorder, and hyperactivity are present in the newest studies. Comprehensive assistance is needed for Sotos syndrome patients in responding to areas of difficulty. There is still a lack of research on the developmental characteristics of these children and the possibilities of improving psychosocial adaptation by providing multidisciplinary long-term medical, educational, and social care.

“Trust Your Gut”: Promising Precision Approaches in Childhood Neuropsychiatric Disorders

The gut-brain axis has been increasingly linked to pediatric neurodevelopmental and neuropsychiatric disorders. Accumulating evidence indicates that there are microbial fingerprints in these conditions, which may lead to personalized therapies. However, few review articles have provided a comprehensive synthesis to guide clinical translation. We aim to summarize current evidence of gut microbiome alterations in these childhood disorders, and opportunities for precision management approaches. There are numerous promising early-life interventions including probiotics and fecal microbial transplants. These treatment modalities may become targeted strategies to reduce both the risk of developing these disorders and their concurrent comorbidity. [ Psychiatr Ann. 2024;54(4):e103–e107.]

Omega-3 Fatty Acid Supplementation Improves Attention Deficit-Hyperactivity Disorder Symptoms in Children

Background: Attention Deficit-Hyperactivity Disorder (ADHD) is one of the most common neuropsychiatric disorders in children. Increasing evidence suggests an association between omega-3 fatty acid and ADHD. We aimed to investigate the effects of 6-month omega- 3 fatty acid supplementation on the fatty-acid profile of erythrocytes and on the clinical severity of ADHD symptoms in children. Methods: Recruitment included 32 children aged 6-14 years diagnosed with ADHD at the Child and Adolescent Psychiatry Department at Ziv Medical Center, Israel. Intervention included refrigerated omega-3 fatty acid supplementation normalized to body weight. Blood samples were taken at baseline, 3 and 6 months after intervention for quantification of fatty acids from erythrocyte membranes. ADHD symptoms were assessed by parents and teachers according to the ADHD Rating-Scale and the Strengths and Difficulties Questionnaire. ADHD severity was additionally assessed by a psychiatrist according to the Clinical Global Impressions Scale. Results: Supplementation of omega-3 fatty acid in children with ADHD raised their omega-3 index statistically significantly from an average of 4.4% omega-3 index at baseline to 11.6% after 6 months and had beneficial effects on ADHD symptoms, as measured by validated questionnaires and in accordance with a pediatric psychiatrist examination. Conclusion: Our pilot study showed that dietary supplementation of omega-3 fatty acid increased the blood omega-3 index levels and improved ADHD symptoms even at the midpoint of 3 months.

Prenatal lipopolysaccharide exposure induces anxiety-like behaviour in male mouse offspring and aberrant glial differentiation of embryonic neural stem cells

BackgroundPrenatal infection has been implicated in the development of neuropsychiatric disorders in children. We hypothesised that exposure to lipopolysaccharide during prenatal development could induce anxiety-like behaviour and sensorineural hearing loss in offspring, as well as disrupt neural differentiation during embryonic neural development.MethodsWe simulated prenatal infection in FVB mice and mouse embryonic stem cell (ESC) lines, specifically 46C and E14Tg2a, through lipopolysaccharide treatment. Gene expression profiling analyses and behavioural tests were utilized to study the effects of lipopolysaccharide on the offspring and alterations in toll-like receptor (TLR) 2-positive and TLR4-positive cells during neural differentiation in the ESCs.ResultsExposure to lipopolysaccharide (25 µg/kg) on gestation day 9 resulted in anxiety-like behaviour specifically in male offspring, while no effects were detected in female offspring. We also found significant increases in the expression of GFAP and CNPase, as well as higher numbers of GFAP + astrocytes and O4+ oligodendrocytes in the prefrontal cortex of male offspring. Furthermore, increased scores for genes related to oligodendrocyte and lipid metabolism, particularly ApoE, were observed in the prefrontal cortex regions. Upon exposure to lipopolysaccharide during the ESC-to-neural stem cell (NSC) transition, Tuj1, Map2, Gfap, O4, and Oligo2 mRNA levels increased in the differentiated neural cells on day 14. In vitro experiments demonstrated that lipopolysaccharide exposure induced inflammatory responses, as evidenced by increased expression of IL1b and ApoB mRNA.ConclusionsOur findings suggest that prenatal infection at different stages of neural differentiation may result in distinct disturbances in neural differentiation during ESC—NSC transitions. Furthermore, early prenatal challenges with lipopolysaccharide selectively induce anxiety-like behaviour in male offspring. This behaviour may be attributed to the abnormal differentiation of astrocytes and oligodendrocytes in the brain, potentially mediated by ApoB/E signalling pathways in response to inflammatory stimuli.

The impact of COVID-19 pandemic on child development: systematic review

The Coronavirus disease 2019 (COVID-19), emerged as a global health issue in December 2019 which lead to the sudden implementation of social distancing norms worldwide, including school closures. This stress scenario can alter physical activity and sleep, which are shown to have a profound impact on brain plasticity. The PubMed, Europe PMC, Google Scholar and Science Direct database was searched between July 1st 2022 and September 20th 2022. The inclusion criteria was a) articles in English, b) Articles with study population as children and the exclusion criteria was a) Articles whose full text couldn't be obtained, b) journals not accessible online. After thorough analysis of 2371 records and removing the studies following the exclusion criteria, a total of 7 studies were included in this review. The results of these studies were tabulated. Among the 4.4 million COVID-19 deaths reported in the MPIDR COVerAGE database, 0.4% occurred in children and adolescents under 20 years of age. Expectant mothers were reluctant to attend clinics and were delayed in seeking treatment, due to the fear of being exposed to the virus. Maternal stress is thought to affect early structures of the developing limbic system. These can be potentially related factors and causes of neuropsychiatric disorders in children. Due to the protracted lockdown’s impact on the economy, food shortages and an increase in food prices resulted in children not receiving the required nutrients. Before being confined to the home, toddlers had more opportunity to advance their motor development at a more complex level while acquiring more communication structures. Information about the impact of lockdown due to an epidemic on motor development of children is relevant to policy makers to aid them in developing strategies to help children cope with epidemic/pandemic-driven adversity and ensure their healthy development.

Prader-Willi syndrome: innovative rehabilitation technologies

The article discusses the rare and difficult to diagnose and treat Prader–Willi syndrome (PWS). The review part of the article presents the issues of its epidemiology, genetic and clinical manifestations of PWS; the role of hypothalamic dysfunction leading to growth hormone defi ciency, hypogonadism, hypothyroidism, adrenal insufficiency, risk of obesity, metabolic syndrome is emphasized. The results of studies concerning speech and intellectual development delay and neuropsychiatric disorders in children with PWS are presented. On the example of clinical observation of a child with this genetic syndrome, along with known methods of treatment, modern possibilities of using innovative rehabilitation technologies, including transcranial micropolarization and bioacoustic correction, are shown.

Is the Latency Between Symptom Onset and Diagnosis a Confounder in Understanding the Potential Relationship Between Intraoperative Blood Pressure and Long-Term Neurodevelopmental and Neuropsychiatric Disorders in Children?

Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, British Columbia, Canada, Vancouver General Hospital, Jim Pattison Pavilion North, [email protected] Funding: Stock options as a consultant for Anesthesia Labs Inc.

Increased Risk of Tourette Syndrome with Leukotriene Modifier Use in Children with Allergic Diseases and Asthma: A Nationwide Population-Based Study.

(1) Background: Cysteinyl leukotriene receptor antagonists (LTRAs), including montelukast and zafirlukast, are FDA-approved for treating pediatric asthma and allergic diseases. Tourette syndrome (TS), a common neuropsychiatric disorder in children, is associated with allergic diseases and asthma. In this study, we investigated the risk of TS following an LTRA prescription for pediatric allergic diseases. (2) Methods: Children younger than 18 years of age who were newly diagnosed with asthma, allergic rhinitis, or atopic dermatitis between 1 January 2005 and 31 December 2018 and who were registered in the Taiwan National Health Insurance Research Database, which comprises the medical records of nearly 23 million Taiwanese population, were enrolled. LTRA users were matched with randomly selected LTRA non-users by sex, age, asthma-diagnosis year, and urbanization level. In total, 26,984 participants with allergic disease and TS were enrolled and included in the Cox proportional hazards model analysis. (3) Results: Children with allergic disease and asthma treated with LTRAs had a higher risk for TS than LTRA non-users (adjusted hazard ratio 1.376 [95% CI: 1.232-1.536], p < 0.001). LTRA users had a significantly higher risk for TS than LTRA non-users with allergic disease. The cumulative incidence of TS was significantly higher in LTRA users than in non-users with allergic diseases and asthma (log-rank test, p < 0.0001). (4) Conclusion: A prescription of LTRAs, mainly montelukast, increased the risk of TS among children with asthma, allergic rhinitis, or atopic dermatitis. The mechanism underlying the neuropsychiatric effect of LTRAs needs further investigation.

6.1 Genetic Concepts You Need to Know

This presentation will introduce genetic vocabulary and research methods that are driving discovery in childhood neuropsychiatric disorders (NDs). We review modern approaches to genetic discovery as a foundation for understanding subsequent presentations that review genetic findings in greater depth.

22.1 Gene Copy Number Variation in Pediatric Mental Health

Rare copy number variants (CNVs) likely play an important role in common childhood neuropsychiatric disorders such as ADHD and OCD. These disorders represent the extremes of broadly distributed behavioral traits that are influenced by underlying variation in fundamental cognitive processes such as response inhibition. Trait-based approaches in a population sample can help reduce heterogeneity and improve the power to detect rare CNVs associated with these disorders. Currently, we do not know the prevalence of CNVs related to neuropsychiatric disorders in youth in the general population.

GENETICS OF CHILDHOOD NEUROPSYCHIATRIC DISORDERS

Both common and rare genetic variants contribute to childhood neuropsychiatric disorders (NPs) such as ADHD, OCD, and ASD. Nevertheless, many questions remain. What is the role of copy number variants (CNVs) to NPs? What is the genetic basis of the commonly observed comorbidity of ADHD with other mental illnesses such as ASD? Are genetic effects mediated by cognitive deficits? Can genetic findings be translated to improve precision medicine?

Atopic dermatitis and risk of major neuropsychiatric disorders in children: A population-based cohort study.

Paediatric atopic dermatitis (AD) has been linked to neuropsychiatric comorbidities such as depression, anxiety and attention-deficit/hyperactivity disorder (ADHD). However, longitudinal data are limited, and the effect of AD severity on neuropsychiatric outcomes requires further characterization. To determine the risk of several major neuropsychiatric conditions in children with AD. We analysed UK health records data in a population-based cohort study. Each patient <18 years old with AD was matched to up to five unaffected patients on age, practice and index date. Treatments served as proxies for AD severity, which was analysed in a time-updated manner. Outcomes were incident anxiety, depression, bipolar disorder, schizophrenia, ADHD, autism, obsessive-compulsive disorder (OCD), suicidal ideation or attempt, and completed suicide. A total of 409,431 children with AD (93.2% mild, 5.5% moderate, 1.3% severe) were compared to 1,809,029 children without AD. In Cox regression models adjusted for age, sex, socioeconomic status and other atopic comorbidities, no statistically significant relationships were observed between AD and incident anxiety (HR 1.01, 95% CI 0.99-1.03), ADHD (1.02, 0.97-1.06), autism (1.02, 0.98-1.06), bipolar disorder (1.08, 0.85-1.36), suicidal ideation/attempt (0.98, 0.95-1.01) or completed suicide (0.85, 0.64-1.14). Children with AD were less likely to develop depression (0.93, 0.91-0.95) or schizophrenia (0.72, 0.54-0.95) but more likely to develop OCD (1.26, 1.16-1.37). However, there was substantial variation by AD severity and age in both the direction and magnitude of effect for many of the neuropsychiatric conditions examined. The was no substantial impact of AD on the overall risk of many neuropsychiatric conditions in children, but disease severity and age may be important modifying factors. Additional research is needed to further dissect the complex relationship between paediatric AD and neuropsychiatric comorbidities.

The therapeutic potential of exercise and caffeine on attention-deficit/hyperactivity disorder in athletes.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by evident and persistent inattention, hyperactivity, impulsivity, and social difficulties and is the most common childhood neuropsychiatric disorder, and which may persist into adulthood. Seventy to 80% of children and adults with ADHD are treated with stimulant medication, with positive response rates occurring for both populations. Medicated ADHD individuals generally show sustained and improved attention, inhibition control, cognitive flexibility, on-task behavior, and cognitive performance. The ethics of ADHD medication use in athletics has been a debated topic in sport performance for a long time. Stimulants are banned from competition in accordance with World Anti-Doping Association and National Collegiate Athletic Association regulations, due to their ability to not only enhance cognitive performance but also exercise performance. Limited research has been conducted looking at the differences in exercise performance variables in unmedicated ADHD verses medicated ADHD. Not all ADHD athletes choose stimulant medication in their treatment plan due to personal, financial, or other reasons. Non-stimulant treatment options include non-stimulant medication and behavioral therapy. However, the use of caffeinated compounds and exercise has both independently been shown to be effective in the management of ADHD symptoms in human studies and animal models. This mini review will discuss the effect of exercise and caffeine on neurobehavioral, cognitive, and neurophysiological factors, and exercise performance in ADHD athletes, and whether exercise and caffeine should be considered in the treatment plan for an individual with ADHD.

Micro-RNAs from Plasma-Derived Small Extracellular Vesicles as Potential Biomarkers for Tic Disorders Diagnosis.

Tic disorders (TDs) are a series of childhood neuropsychiatric disorders characterized by involuntary motor and/or vocal tics and commonly comorbid with several other psychopathological and/or behavioral disorders (e.g., attention deficit hyperactivity disorder and obsessive–compulsive disorder), which indeed aggravate clinical symptoms and complicate diagnosis and treatment. Micro-RNAs (miRNAs) derived from small extracellular vesicles (sEVs) have been recognized as novel circulating biomarkers of disease. To identify specific miRNAs derived from plasma sEVs for TDs’ diagnosis and prognosis, we used official EV isolation and purification methods to characterize the plasma-derived EV miRNAs from children with different types of TDs. Nanoparticle tracking analysis, transmission electron microscopy, and immunoblot analysis of EV surface markers were applied to confirm the features and quality of sEVs. The RNA sequencing (RNA-seq) approach was adapted to identify novel circulating sEVs-derived miRNAs with altered expression levels in paired comparisons of TDs versus healthy controls (HCs), transient tic disorder (TTD) versus chronic motor or vocal tic disorder (CTD), and TTD versus Tourette Syndrome (TS). GO term and KEGG pathway were performed for functional analysis and the receiver operator curve analysis was followed to test the diagnosis efficacy of differentially expressed miRNAs (DEMs) derived from plasma sEVs among paired groups, namely, TDs versus HCs, TTD versus CTD, and TTD versus TS. As a result, 10 miRNAs (hsa-let-7a, hsa-let-7b, hsa-let-7c, hsa-let-7e, hsa-let-7f, hsa-miR-25-3p, hsa-miR-29a-3p, hsa-miR-30b-5p, hsa-miR-125b-5p, and hsa-miR-1469) have demonstrated a significantly different expression signature in the TDs group compared to HCs with excellent area under curve (AUC) values of 0.99, 0.973, 0.997, 1, 0.99, 0.997, 0.987, 0.993, 0.977, and 0.997, respectively, and the diagnostic efficacy of miRNAs was also estimated for discriminating TTD from CTD or TS. In our research, we finally obtained several potential sEVs-derived miRNA biomarkers to assess the diagnosis and prognosis of TDs.

Sex-specific association between placental inflammatory cytokine mRNA expression and preschoolers’ behavioral development: The Ma’anshan birth cohort study

BackgroundPlacental inflammation may contribute to brain abnormalities and childhood neuropsychiatric disorders, but limited knowledge is available on the association of placental inflammatory cytokine levels and offspring’s behavioral development. This study aimed to examine the sex-specific association between placental inflammatory cytokine mRNA expression and preschoolers’ behavioral development. Methods3474 pregnant women were recruited as the initial study population in the Ma’anshan birth cohort (MABC) study. Placentas (n = 2519) were collected during childbirth, and the mRNA expression of IL-8, IL-1β, CRP, TNF-α, IL-6, IL-10, and IL-4 was assessed. The Child Behavior Checklist 1.5–5 (CBCL 1.5–5) was used to assess children’s behavioral development at 4 years old. A T-score ≥ 60 on summary scales or a score ≥ 65 on syndrome scales was regarded as the borderline clinical range. Multiple linear regression models and binary logistic regression models were applied to explore the sex-specific associations between placental inflammatory cytokines mRNA transcript levels and preschoolers’ behavioral development. ResultsSex-specific associations between placental inflammatory cytokines mRNA expression and preschoolers’ behavioral development were observed. There was a positive association between IL-8 and CBCL scores for boys on anxious/depressed problems, aggressive behaviors, externalizing problems and total problems. Logistic regression models showed that high levels of IL-8 were associated with a higher risk of girls’ emotionally reactive problems and sleep problems compared to low/medium levels. High TNF-α was correlated with increased sleep problem scores in boys, and medium TNF-α (vs. low levels) was associated with an increased risk of girls’ externalizing problems. Medium levels of CRP, IL-1β, and IL-6 were found to be associated with a decreased risk of girls’ behavioral problems compared to low/high levels. For anti-inflammatory cytokines, medium IL-10 and IL-4 (vs. low levels) were observed to be associated with a lower risk of internalizing problems in boys and externalizing problems in girls, respectively. High IL-10 was correlated with decreased attention problem scores in boys. ConclusionThis study indicates that placental inflammatory cytokine mRNA expression of IL-8, CRP, TNF-α, IL-1β, IL-4 and IL-10 may be associated with preschoolers’ behavioral development in a sex-specific manner.

Linking aberrant pauses during object naming to letter and word decoding speed in elderly with attention complaints

Attention deficit and reading difficulty are often comorbid in neuropsychiatric disorders of childhood and adolescence. Although recent research has shown how these two domains may interact in children, knowledge about such interaction in elderly is lacking. The present study tested whether this association is also present in healthy elderly with undiagnosed attention problems. Thirty-two subjects (65+ years) with life-long complaints of attention and with a Mini Mental (MMSE) cutoff of 27 points were tested with MapCog Spectra (MCS), with a word recognition test (Word Chains test) and CANTAB subtests of attention. All tests were presented on a tablet, except for the Word Chains test. The participants mean MMSE score was 29 points and their mean age was 71.5 years. Strong correlations were seen between the Word Chains test and the MCS, suggesting that a high number of aberrantly long pauses during serial naming was associated with fewer identifications of letters, words and sentences. The number of aberrant pauses was also associated with slower Reaction Time and a lower score on the Attention Shifting task of the CANTAB. The results were not associated with either gender or general intelligence. This study shows that attention is linked to decoding speed irrespective of intelligence and gender. We therefore suggest that a clinical assessment of attention deficit should also include an assessment of decoding ability, and vice versa, as these cognitive functions are strongly interdependent.

Treatment of Cognitive and Behavioral Disorders in Children Using Transcranial Magnetic Stimulation: Literature Review

Speech disorders have the leading position among cognitive disorders and represent the urgent medical problem. The modern approach to the treatment of cognitive and behavioral disorders in children consists of the integrity of pharmacotherapeutic, correctional and psychotherapeutic, as well as non-invasive instrumental methods of brain neurostimulation. This article provides the overview of the currently available data on transcranial magnetic stimulation method as noninvasive treatment of various neuropsychiatric disorders in children and its difference from physiotherapeutic methods used in traditional Russian practice.

Altered Variability and Concordance of Dynamic Resting-State fMRI Indices in Patients With Attention Deficit Hyperactivity Disorder.

Objective: Attention deficit hyperactivity disorder (ADHD) is a commonly diagnosed neuropsychiatric disorder in children, which is characterized by inattention, hyperactivity and impulsivity. Using resting-state functional magnetic resonance imaging (R-fMRI), the alterations of static and dynamic characteristics of intrinsic brain activity have been identified in patients with ADHD. Yet, it remains unclear whether the concordance among indices of dynamic R-fMRI is altered in ADHD.Methods: R-fMRI scans obtained from 50 patients with ADHD and 28 healthy controls (HC) were used for the current study. We calculated the regional dynamic changes in brain activity indices using the sliding-window method and compared the differences in variability of these indices between ADHD patients and HCs. Further, the concordance among these dynamic indices was calculated and compared. Finally, the relationship between variability/concordance of these indices and ADHD-relevant clinical test scores was investigated.Results: Patients with ADHD showed decreased variability of dynamic amplitude of low-frequency fluctuation (dALFF) in the left middle frontal gyrus and increased one in right middle occipital gyrus, as compared with the HCs. Besides, ADHD patients showed decreased voxel-wise concordance in the left middle frontal gyrus. Further, lower voxel-wise concordance in ADHD’s left middle frontal gyrus was associated with more non-perseverative errors in Wisconsin Card Sorting Test, which reflects worse cognitive control.Conclusion: Our findings suggest that variability and concordance in dynamic brain activity may serve as biomarkers for the diagnosis of ADHD. Further, the decreased voxel-wise concordance is associated with deficit in cognitive control in ADHD patients.

Evaluating Therapeutic Effects of ADHD Medication Objectively by Movement Quantification with a Video-Based Skeleton Analysis.

Attention-deficit/hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in children. Several scales are available to evaluate ADHD therapeutic effects, including the Swanson, Nolan, and Pelham (SNAP) questionnaire, the Vanderbilt ADHD Diagnostic Rating Scale, and the visual analog scale. However, these scales are subjective. In the present study, we proposed an objective and automatic approach for evaluating the therapeutic effects of medication in patients with (ADHD). The approach involved using movement quantification of patients’ skeletons detected automatically with OpenPose in outpatient videos. Eleven skeleton parameter series were calculated from the detected skeleton sequence, and the corresponding 33 features were extracted using autocorrelation and variance analysis. This study enrolled 25 patients with ADHD. The outpatient videos were recorded before and after medication treatment. Statistical analysis indicated that four features corresponding to the first autocorrelation coefficients of the original series of four skeleton parameters and 11 features each corresponding to the first autocorrelation coefficients of the differenced series and the averaged variances of the original series of 11 skeleton parameters significantly decreased after the use of methylphenidate, an ADHD medication. The results revealed that the proposed approach can support physicians as an objective and automatic tool for evaluating the therapeutic effects of medication on patients with ADHD.