SEARCH · PubMed Health

Results for “Neurodevelopmental Disorders”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources

PubMed2001

Mental development in polysomy X Klinefelter syndrome (47,XXY; 48,XXXY): effects of incomplete X inactivation.

The child with XXY or a variant form is a fertile ground for scientific investigation because of the homogeneity of the disorder and the increased prevalence of learning disorders associated with it. However, the research studies of boys with XXY (Klinefelter syndrome) have been plagued by a variety of factors from small sample size, methodological flaws, and ascertainment bias. In spite of these shortcomings, there remains some consistency to the neurobehavioral profile of this disorder. In general, the prenatal population of boys with XXY is less affected developmentally and is more academically successful than the boys identified through postnatal diagnosis. Boys with XXY often have decreased muscle tonus, delayed speech, and language skills with an increased incidence of reading differences and dyslexia. It does appear that social difficulties may be mediated by language processing problems and temperamental issues. The neurobehavioral and neurocognitive phenotype of boys with XXY places them at risk for school failure and secondary behavioral disturbances. Therefore, early evaluation and intervention is strongly recommended since the prognosis may be improved significantly with appropriate therapeutic intervention. The natural history of this disorder is not well defined from the neurodevelopmental, neuroimaging, and cytogenetic perspective. Further investigation into the effects and the relationships between parental origin and outcome may provide many answers regarding the variability of the disorder. Lastly, some promising theories have been postulated regarding the neurobiological etiology of this disorder, which requires more investigation if we are to understand the pathogenesis of this XXY and its effect on learning.

Aneuploidy↗

PubMed2006

Preadolescent conduct problems in girls and boys.

OBJECTIVE: To examine sex differences in correlates of disruptive behavior disorders (DBDs) in preadolescent children using indicators of a wide range of well-established risk factors for DBDs and outcomes 3 years after initial assessment. METHOD: Analyses were based on data for 5- to 10-year-olds (n = 5,913) from the British Child and Adolescent Mental Health Survey 1999, and a 3-year follow-up of selected subsamples (n = 1,440) at ages 8 through 13 years. DSM-IV diagnoses were assigned using the Developmental and Well-Being Assessment at both contacts. RESULTS: Boys and girls were equally exposed to most social and family risks for DBDs, with little evidence of differential sensitivity to these risks. Boys were exposed more to neurodevelopmental difficulties, attention-deficit/hyperactivity disorder, and peer problems and had lower rates of prosocial behaviors; together, these factors and physical punishment could account for 54% of the observed sex differences in DBDs. At follow-up, outcomes for girls and boys with DBDs were very similar. For children with subthreshold conduct problems at initial assessment, boys were more likely to go on to exhibit DBDs than were girls (25% versus 7%). CONCLUSIONS: Sex differences in the levels of a variety of child characteristics and interpersonal factors are likely to be important in understanding sex differences in risk for DBDs in preadolescent samples.

Adolescent↗

PubMed2005

Premorbid intellectual functioning in bipolar disorder and schizophrenia: results from a cohort study of male conscripts.

OBJECTIVE: Premorbid intellectual impairment has been described in schizophrenia, but little is known about premorbid intellectual functioning in bipolar disorder or other psychoses. In this study, premorbid intellectual ability was investigated in individuals with bipolar disorder, schizophrenia, or other psychoses. METHOD: Results on verbal, arithmetic, and visuospatial reasoning tests were obtained for 195,019 apparently healthy male subjects conscripted into the Finnish Defense Forces during 1982-1987 (mean age, 19.9 years). Linkage with the Finnish Hospital Discharge Register (mean follow-up time, 7.1 years) identified conscripts later diagnosed with bipolar disorder (N=100), schizophrenia (N=621), or other psychoses (N=527). RESULTS: Poor performance on the visuospatial reasoning test at age 20 was associated with higher risks for all three disorders. The odds ratios indicating the difference in risk of illness between the lowest and highest of nine performance categories were 34.65 (95% confidence interval [CI], 4.05-296.44) for bipolar disorder, 13.76 (95% CI=5.49-34.47) for schizophrenia, and 4.28 (95% CI=2.09-8.77) for other psychoses. In contrast, the higher the score for arithmetic reasoning, the greater the risk of bipolar disorder; a high score was associated with a more than 12-fold greater risk. Verbal test performance was not associated with higher risk for psychiatric disorder. CONCLUSIONS: These results indicate that premorbid visuospatial reasoning is impaired in bipolar disorder and schizophrenia and, to a smaller extent, in other psychoses. This suggests that a subtle neurodevelopmental aberration is involved in the etiology of bipolar disorder and schizophrenia. High arithmetic test performance may be associated with greater risk for bipolar disorder.

Adult↗

PubMed2000

Clinical trials of controlled-release melatonin in children with sleep-wake cycle disorders.

This is the first study to examine effective doses of controlled-release (CR) melatonin in children with chronic sleep wake cycle disorders. All 42 subjects had severe neurodevelopmental difficulties. Initially, a randomized double-blinded cross-over design was used in 16 children, comparing the effectiveness of fast-release (FR) and CR melatonin. In the remainder of the patients, the CR melatonin was studied on a clinical basis. The effectiveness of treatment was assessed by sleep charts and clinical follow-up. Emphasis was placed on the judgement of the parents, who had guidance from the physicians. The average final CR melatonin dose in the 42 patients was 5.7 mg (2-12 mg). The studies showed that the FR melatonin was most effective when there was only delayed sleep onset, but CR formulations were more useful for sleep maintenance. Children appeared to require higher doses than adults.

Adolescent↗

PubMed2026

CRISPR-Enabled functional genomics in hPSCs-derived neural models for autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a genetically heterogeneous neurodevelopmental condition in which hundreds of individually rare risk variants converge on a small number of shared biological pathways, including synaptic scaffolding, chromatin remodeling, excitation-inhibition balance, and cellular energy metabolism. Translating this genetic heterogeneity into mechanistic insight requires experimental systems capable of interrogating individual gene functions in human-relevant neural contexts at scale. CRISPR-enabled functional genomics in human pluripotent stem cell (hPSC)-derived neural models, spanning neural progenitors, cortical and inhibitory neurons, astrocytes, microglia, and brain organoids, provides precisely this capability. By integrating pooled perturbation screens with multimodal readouts including single-cell and spatial transcriptomics, chromatin accessibility profiling, proximity labeling proteomics, multi-electrode array electrophysiology, and metabolic flux analysis, these platforms enable systematic, causal mapping of ASD gene function at system resolution. Early applications have already revealed convergent mechanisms: BAF complex disruption expands the ventral progenitor pool and biases its fate toward oligodendrocyte and interneuron lineages; ADNP loss impairs microglial synaptic pruning through altered endocytic trafficking; and mTOR pathway dysregulation in PTEN- and TSC2-perturbed models links genetic risk directly to metabolic and mitochondrial dysfunction. Computational frameworks including MIMOSCA and SCEPTRE enable causal network reconstruction and pseudotime inference from these datasets, moving the field from gene lists toward pathway-level models of ASD pathobiology. Translational applications leverage isogenic iPSC panels and variant-level base and prime editing to stratify ASD variants by functional impact, informing gene therapy design for haploinsufficient targets such as CHD8 and SCN2A via AAV or antisense oligonucleotide delivery. Remaining challenges, including model developmental immaturity, batch variability, and the difficulty of modeling polygenic risk, are addressed by a roadmap integrating spatial perturbomics, AI-driven causal inference, and population-scale standardized biobanks. This review synthesizes the current state of CRISPR-based functional genomics in human stem cell neural models as a coherent experimental framework for converting ASD genetic associations into mechanistic understanding and therapeutic opportunity.

Humans↗

PubMed2004

Elevated rates of schizophrenia in a familial sample with mental illness and intellectual disability.

BACKGROUND: It is unknown whether intellectual disability (ID) is more familially related to psychotic mood disorders or schizophrenia. L. S. Penrose's large sample of families with two or more members admitted to psychiatric hospitals provided a unique opportunity to investigate the familial relationship between mild ID, schizophrenia and psychotic affective disorders. METHOD: There were 183 affected relative pairs comprising probands with mild ID (95 male, 88 female) and their first or second degree relatives with schizophrenia or psychotic affective disorder. RESULTS: There were nearly twice as many relatives with a diagnosis of schizophrenia (n = 121) as relatives with affective disorders (n = 62) among the intellectually impaired probands. This excess of schizophrenia was statistically significant, even after accounting for the increased risk of hospitalization for schizophrenia (P = 0.005), and was fairly constant across the different relative types. First-degree relatives with either mental illness were more likely to be parents (n = 77) than siblings (n = 51) or children (n = 3), but there was no excess of mother-son pairs. CONCLUSIONS: These results suggest a stronger familial relationship of ID with schizophrenia than psychotic affective disorder, and lend some support to the neurodevelopmental hypothesis of schizophrenia.

Adult↗

PubMed2022

TTC5 syndrome: Clinical and molecular spectrum of a severe and recognizable condition.

Biallelic mutations in the TTC5 gene have been associated with autosomal recessive intellectual disability (ARID) and subsequently with an ID syndrome including severe speech impairment, cerebral atrophy, and hypotonia as clinical cornerstones. A TTC5 role in IDs has been proposed based on the physical interaction of TTC5 with p300, and possibly reducing p300 co-activator complex activity, similarly to what was observed in Menke-Hennekam 1 and 2 patients (MKHK1 and 2) carrying, respectively, mutations in exon 30 and 31 of CREBBP and EP300, which code for the TTC5-binding region. Recently, TTC5-related brain malformation has been linked to tubulinopathies due to the function of TTC5 in tubulins' dynamics. We reported seven new patients with novel or recurrent TTC5 variants. The deep characterization of the molecular and phenotypic spectrum confirmed TTC5-related disorder as a recognizable, very severe neurodevelopmental syndrome. In addition, other relevant clinical aspects, including a severe pre- and postnatal growth retardation, cryptorchidism, and epilepsy, have emerged from the reversal phenotype approach and the review of already published TTC5 cases. Microcephaly and facial dysmorphism resulted in being less variable than that documented before. The TTC5 clinical features have been compared with MKHK1 published cases in the hypothesis that clinical overlap in some characteristics of the two conditions was related to the common p300 molecular pathway.

Exons↗

PubMed2003

Profile of childhood epilepsy in Bangladesh.

Very little is known about childhood epilepsies in Bangladesh. This study was conducted within a national children's hospital in Dhaka city to provide baseline information on diagnosis and clinical outcomes of 151 children (98 males, 53 females, age range between 2 months to 15 years, median age of 3 years). Participants who presented with recurrent unprovoked seizures were followed up in an epilepsy clinic for at least 1 year. Of presenting families, 68.3% were from middle-income and lower-income groups. A history of perinatal asphyxia and neonatal seizures was present in 46.4% and 41.1% of participants respectively. Generalized, partial, and unclassifiable epilepsy were found in 63.6%, 25.2%, and 11.2% respectively. Severe outcome (malignant) epilepsy syndromes were diagnosed in 14.6%. Symptomatic epilepsy was found in 61%. Poor cognitive development was present in 72.8% and poor adaptive behaviour in 57%. Poor seizure remission occurred in 50.3%. Factors most predictive of poor seizure remission were: multiple types of seizures, poor cognition at presentation, high rates of seizures, associated motor disability, and EEG abnormalities. The study suggests that most children presenting at tertiary hospitals for seizure disorders come late and with associated neurodevelopmental morbidities. Specialized services are needed closer to their homes. The process for establishing early referral and comprehensive management of childhood epilepsies in Bangladesh requires further study.

Adolescent↗

PubMed1994

Visual outcome of low-birth-weight infants (1500-2500 g) at one year of corrected age.

Visual functions (grating acuity, visual field size, optokinetic nystagmus and eye alignment) were tested as part of a longitudinal study in 96 low-birth-weight infants (birth weight 1500-2500 g) at one year of corrected age. Except for optokinetic nystagmus, deficit rates of all visual functions were low, and the obtained values comparable with normal age values in full-term infants. Effects of gestational duration, birth weight and intrauterine growth retardation on visual functions could not be demonstrated. Some perinatal risk factors (mechanical ventilation, oxygen treatment for more than one day, the presence of maternal hypertensive disorders) and a less-optimal neurodevelopmental status at one year had a negligible effect on visual field size. The observed deficits are not likely to cause disability. Low-birth-weight infants appeared not to be at risk for developing visual deficits at one year of corrected age.

Birth Weight↗

PubMed2004

Mercury exposure and child development outcomes.

Mercury is ubiquitous in the global environment, ensuring universal exposure. Some forms of mercury are especially neurotoxic, including clinical signs at high doses. However, typical human exposures occur at low to moderate doses. Only limited data about neurotoxicity at low doses are available, and scientists differ in their interpretation. Dose-response data on neurodevelopment are particularly limited. Despite or perhaps because of the lack of sufficient or consistent scientific data, public concern about a link between mercury exposure and developmental disabilities has been rising. After reviewing the data, the US Environmental Protection Agency proposed a reference dose (an estimate of a daily dose that is likely to be without a risk of adverse effects over a lifetime) for methyl mercury that is substantially lower than previous guidelines from the World Health Organization, the US Agency for Toxic Substances and Disease Registry, and the US Food and Drug Administration. Some questions have been raised about the Environmental Protection Agency's guidelines, but the issue remains unresolved. Meanwhile, consumer groups have raised questions about the potential link between mercury exposure and autism spectrum disorders as well as other adverse neurodevelopmental outcomes. This hypothesis has prompted some parents to seek regulatory, legal, or medical remedies in the absence of firm evidence. This article reviews what is known about mercury neurotoxicity and neurodevelopmental risk. Our intent is to focus the debate about mercury on 1) additional research that should be sought and 2) defining the principal issues that public policy makers face.

Child↗

PubMed2026

Bi-allelic loss-of-function variants in JKAMP cause a neurodevelopmental syndrome associated with dysregulation of GPR37 trafficking.

The endoplasmic reticulum (ER) serves as a key hub for protein homeostasis, maintaining a strict quality-control system that ensures only properly folded proteins reach their destinations, while misfolded proteins are degraded via ER-associated degradation (ERAD) or selective ER-phagy. JKAMP, which encodes an ER-resident transmembrane protein involved in ERAD, has not previously been associated with human disease. Here, we report bi-allelic loss-of-function variants in JKAMP in 14 affected individuals from 10 unrelated families presenting with a neurodevelopmental syndrome characterized by intellectual disability, developmental delay, seizures, hypotonia, microcephaly, and dysmorphic features. An in vivo zebrafish model lacking jkamp recapitulated key aspects of the human disorder, including developmental abnormalities and impaired myelin production, further corroborating its pathogenic role. Mechanistic studies identified GPR37, a brain-enriched orphan G protein-coupled receptor (GPCR) and known JKAMP interactor, as a critical downstream effector. GPR37 plays essential roles in dopaminergic signaling, inflammatory pain regulation, neuroprotection, and myelination. Loss of JKAMP resulted in defective folding and degradation of GPR37, leading to its accumulation within the ER and impaired trafficking to the plasma membrane, likely due to impaired ER quality control. These findings establish JKAMP as a previously unrecognized contributor to human neurodevelopment and uncover a pathogenic mechanism linking ER protein quality control to GPCR regulation and neurological disease.

Humans↗

PubMedDate not supplied

[Neurodevelopmental theories of schizophrenia--preclinical studies].

Schizophrenia is a complex disorder of unknown origin, characterised by abnormalities in the realms of perception, thinking and the experience of emotions that onset is restricted to young adulthood. Many techniques that range from neuropathology to neuroimaging identified subtle brain abnormalities particularly in frontal, temporal cortex, hippocampus, basal ganglia and cerebellum. Neurodevelopmental models of schizophrenia test hypotheses that this disease is caused by a defect in cerebral development which results in altered neural connectivity, brain neurochemistry and aberrant behaviour observed in adult life. Recent evidence indicates that neonatal hippocampal damage may affect prefrontal neuronal integrity. The developmental lesion model appears to have predictive validity because treatment with antipsychotic drugs normalises some abnormal behaviour changes. Therefore it will be a useful paradigm in the work on new therapies and in providing new insights about pathophysiology and etiology of schizophrenia.

Adult↗

PubMed2006

Ethanol sensitization in a neurodevelopmental lesion model of schizophrenia in rats.

Substance use disorder comorbidity in schizophrenia may reflect dysfunctional cortical-striatal-limbic circuitry commonly involved in the addiction process and the pathogenesis of schizophrenia. Rats with neonatal ventral hippocampal lesions (NVHL) demonstrate post-adolescent onset of schizophrenia-like symptoms and increased addiction vulnerability in paradigms using cocaine in adulthood. Here, we investigated response profiles of young adult NVHL vs. SHAM rats to ethanol, an addictive drug with many psychopharmacological effects divergent from those of cocaine, in a locomotor sensitization paradigm. Over 15 days of daily injections of saline, low (0.15 g/kg) or high (1.0 g/kg) doses of ethanol, NVHL rats showed stimulatory effects at the low dose compared to saline and high-dose conditions, while SHAM rats showed expected patterns of dose-dependent suppression of locomotor activity. In a challenge session 2 weeks later in which a moderate dose (0.25 g/kg) of ethanol was given to all subjects, NVHL rats with history of prior ethanol exposure showed greater locomotor activity consistent with installment of alcohol-induced sensitization not present in SHAMs. These findings provide further evidence of enhanced short- and long-term responsivity to abused drugs in a neurodevelopmental model of schizophrenia, and may reflect potentiation of common mechanisms of addiction shared between pharmacologically diverse addictive drugs.

Animals↗

PubMed1997

Substantia innominata: a notion which impedes clinical-anatomical correlations in neuropsychiatric disorders.

Comparative neuroanatomical investigations in primates and non-primates have helped disentangle the anatomy of the basal forebrain region known as the substantia innominata. The most striking aspect of this region is its subdivision into two major parts. This reflects the fundamental organizational scheme for this portion of the forebrain. According to this scheme, two major subcortical telencephalic structures, i.e. the striatopallidal complex and extended amygdala, form large diagonally oriented bands. The rostroventral extension of the pallidum accounts for a large part of the rostral subcommissural substantia innominata, while the sublenticular substantia innominata is primarily occupied by elements of the extended amygdala. Also dispersed across this region is the basal nucleus of Meynert, which is part of a more or less continuous collection of cholinergic and non-cholinergic corticopetal and thalamopetal cells, which stretches from the septum diagonal band rostrally to the caudal globus pallidus. The basal nucleus of Meynert is especially prominent in the primate, where it is sometimes inappropriately applied as a synonym for the substantia innominata, thereby tacitly ignoring the remaining components. In most mammals, the extended amygdala presents itself as a ring of neurons encircling the internal capsule and basal ganglia. The extended amygdala may be further subdivided, i.e. into the central extended amygdala (related to the central amygdaloid nucleus) and the medial extended amygdala (related to the medial amygdaloid nucleus), which generally form separate corridors both in the sublenticular region and along the supracapsular course of the stria terminalis. The extended amygdala is directly continuous with the caudomedial shell of the accumbens, and to some extent appears to merge with it. Together the accumbens shell and extended amygdala form an extensive forebrain continuum, which establishes specific neuronal circuits with the medial prefrontal-orbitofrontal cortex and medial temporal lobe. This continuum is particularly characterized by a prominent system of long intrinsic association fibers, and a variety of highly differentiated downstream projections to the hypothalamus and brainstem. The various components of the extended amygdala, together with the shell of the accumbens, are ideally structured to generate endocrine, autonomic and somatomotor aspects of emotional and motivational states. Behavioral observations support this proposition and demonstrate the relevance of these structures to a variety of functions, ranging from the various elements of the reproductive cycle to drug-seeking behavior. The neurochemical and connectional features common to the accumbens shell and the extended amygdala are especially relevant to understanding the etiology and treatment of neuropsychiatric disorders. This is discussed in general terms, and also in specific relation to the neurodevelopmental theory of schizophrenia and to the neurosurgical treatment of neuropsychiatric disorders.

Animals↗

PubMed2000

Functional outcomes in self-care, mobility, communication, and learning in extremely low-birth weight infants.

Gaps have existed in specifying degrees of severity of cerebral palsy assessment of self-care and communicative competencies, and specifying age-appropriate preschool educational and behavioral competencies. Imbedded in the concept of measuring functional status is the interaction between health and neurologic impairments, developmental challenges and competencies, family resources and disadvantages, and the child's current status. In reviewing historic outcomes of severe ROP over the past 40 years, it was noted that severe ROP caused blindness in 2% to 11% of survivors. There was a constant observation that approximately 50% of severe ROP survivors with blindness had multiple functional and developmental challenges beyond blindness alone. Similarly, in reviewing outcomes of cerebral palsy, it is imperative to describe the severity of cerebral palsy and functional consequences in motor, selfcare, communication, and learning. The reason to measure the functional status of children with neurodevelopmental impairments before first grade is that the degrees of severity of these disorders can be specified before attending school with peers. Subtler aspects of neurodevelopmental impairments need to assess impact on literacy, information learning, written language, social competencies with peers, and recreational and community participation. In this way, we can understand the vulnerabilities and resiliences of children and families of VLBW and ELBW status. This is a critical step in understanding long-term quality of life and independent living issues. In addition, our efforts can address those factors and pathways whereby multiple disabilities and multiple functional limitations cluster. Our biomedical intervention can prioritize strategies that lessen severe multiple disabilities and simultaneously support families, when despite our best efforts functional challenges are life long.

Activities of Daily Living↗

PubMed1995

Changes of brain anatomy in patients with posttraumatic stress disorder: a pilot magnetic resonance imaging study.

No abnormalities in magnetic resonance images were recorded in patients with posttraumatic stress disorder other than an increased incidence (50%) of a small cleft in the callosal-septal interface, a cavum of the septum pellucidum. A similar grade of cavum was obtained in 14% of normal volunteers matched for age, socioeconomic background, and military experience. The cavum is believed to have antedated the disorder and is conceived to be a neurodevelopmental aberration. The possibility that the cavum is a marker of vulnerability to stress in psychopathology is discussed.

Adult↗

PubMed1997

Brain abnormalities in schizophrenia-spectrum children: implications for a neurodevelopmental perspective.

Children with symptoms of schizophrenia-spectrum disorder (N = 20) were compared to controls (N = 20) matched for age and socioeconomic status. Structural brain abnormalities were assessed with magnetic resonance imaging and functional brain abnormalities with neuropsychological tests. Children with schizophrenia-spectrum disorder had smaller amygdala and temporal cortex volumes, along with reduced callosal areas and an unusual pattern of neuroanatomic asymmetries. No differences were noted in overall brain volume, ventricular volume, hippocampal volume, or frontal area. Schizophrenia-spectrum children were also characterized by deficits in all neuropsychological functions examined. Some types of verbal memory and frontal lobe skills were especially deficient. These results support the hypothesis that children with schizophrenia-spectrum disorder have significant brain abnormalities, similar in some ways to those seen in adult schizophrenics. In conjunction with recent primate studies, the current results draw attention to the role of the amygdala as one relevant factor in the pathogenesis of schizophrenia.

Brain↗

PubMed2005

Neurodevelopmental implications of ocular motor apraxia.

Ocular motor apraxia (OMA), a disorder of saccadic initiation, may be congenital or acquired. While the acquired form is frequently associated with significant neuropathology, the congenital form is often regarded as relatively benign. Many children with congenital OMA who were observed clinically have shown neurodevelopmental disturbance over time. A retrospective review was taken of 34 consecutive patients (22 males and 12 females), seen over a 20-year period, to evaluate the frequency and type of associated neurodevelopmental problems. Age at presentation ranged from 8 weeks to 14 years, with a mean age of 10 years. Of 29 children with congenital OMA, 15 had imaging evidence of structural central nervous system abnormalities (with cerebellar hypoplasia the most frequent abnormality detected). Eleven of the 14 patients with no structural abnormality showed abnormal neurodevelopment. This study suggests that congenital OMA is not a benign diagnosis, even in the absence of overt neurological disturbance at the time of presentation.

Adolescent↗