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 1,189 records · Page 66Linked to original sources

PubMed2003

The axonal chemorepellant semaphorin 3A is increased in the cerebellum in schizophrenia and may contribute to its synaptic pathology.

The neuropathological features of schizophrenia are suggestive of a developmentally induced impairment of synaptic connectivity. Semaphorin 3A (sema3A) might contribute to this process because it is a secreted chemorepellant which regulates axonal guidance. We have investigated sema3A in the cerebellum (an area in which expression persists in adulthood), and measured its abundance in 16 patients with schizophrenia and 16 controls. In adults, sema3A was predominantly localized to the inner part of the molecular layer neuropil, whereas infants and rats showed greater labelling of Purkinje cell bodies. Sema3A was increased in schizophrenia, as shown by enzyme-linked immunosorbent assay (+28%; P<0.05) and immunohistochemistry (+45%; P<0.01). We also measured reelin mRNA, since reelin is involved in related developmental processes and is decreased in other brain regions in schizophrenia. Reelin mRNA showed a trend reduction in the subjects with schizophrenia (-26%; P=0.07) and, notably, was negatively correlated with sema3A. Sema3A also correlated negatively with synaptophysin and complexin II mRNAs. The results show that sema3A is elevated in schizophrenia, and is associated with downregulation of genes involved in synaptic formation and maintenance. In this respect, sema3A appears to contribute to the synaptic pathology of schizophrenia, perhaps via ongoing effects of persistent sema3A elevation on synaptic plasticity. The findings are consistent with an early neurodevelopmental origin for the disorder, and the reciprocal changes in sema3A and reelin may be indicative of a pathogenic mechanism that affects the balance between trophic and inhibitory factors regulating synaptogenesis.

Adaptor Proteins, Vesicular Transport↗

PubMed2003

Interstitial white matter neurons express less reelin and are abnormally distributed in schizophrenia: towards an integration of molecular and morphologic aspects of the neurodevelopmental hypothesis.

Two main pieces of neurobiological evidence are adduced to support an early neurodevelopmental component to schizophrenia. Firstly, an abnormal distribution of neurons, especially interstitial white matter neurons (IWMNs). Secondly, decreased expression of reelin, a key developmental signalling molecule. Although influential, neither result is wholly established, and a possible link between them has not been examined. We addressed both issues, in superior temporal cortex, in 12 subjects with schizophrenia and 14 controls. The distribution and density of IWMNs, immunostained with the neuronal marker NeuN, was increased in the superficial white matter in schizophrenia (+16%; P=0.03). IWMN density in deep white matter was unaffected. Using in situ hybridization, reelin mRNA was found to be expressed by many IWMNs, layer I neurons, and scattered interneurons. Superficial IWMNs (P=0.008) and layer I neurons (P=0.036) both expressed less reelin mRNA per cell in schizophrenia, with a trend for deep IWMNs (P=0.055). In conclusion, we replicated findings of increased IWMN density, and of decreased reelin expression, in schizophrenia. The loss of reelin reflects, at least partly, its decreased expression by IWMNs. These findings together support neurodevelopmental theories of the disorder, and indicate a link between reelin and IWMNs in this process, consistent with evidence from the heterozygous reeler mutant mouse. The alterations may contribute to the aberrant synaptic connectivity seen in schizophrenia. However, the functional implications of the abnormalities, as well as the mechanisms involved, remain to be fully elucidated.

Aged↗

PubMed2003

Long-term behavioural, molecular and morphological effects of neonatal NMDA receptor antagonism.

Brief N-methyl-D-aspartate (NMDA) receptor blockade in neonatal rats has been reported to increase neuronal apoptosis. We replicated this finding using MK-801 (0.5 mg/kg) administered twice on postnatal day 7, and then studied the long-term consequences. In adulthood, treated rats showed reduced volume and neuronal number within the hippocampus, and altered hippocampal NMDA receptor (NR1 subunit) expression. Synaptophysin mRNA was decreased in the thalamus (laterodorsal nucleus). Adult MK-801-treated females had prepulse inhibition deficits and increased locomotor activity. The data show that a transient and limited glutamatergic intervention during development can have chronic behavioural, structural and molecular effects. The effects are reminiscent of alterations reported in schizophrenia and, as such, are consistent with hypotheses advocating a role for NMDA receptor hypofunction, and aberrant apoptosis, in the neurodevelopmental pathogenesis of the disorder.

Animals↗

PubMed2001

Neurodevelopmental and behavioural characteristics in learning disabilities and attention deficit disorder.

Specific learning disability in childhood is frequently associated with attention deficit disorder. The distinction between children with and without such comorbidity is often difficult to make. Our aim was to delineate the neurocognitive and behavioural differences between children with specific learning disabilities, with and without attention deficit. Students diagnosed with learning disability, mean age 8.3, 1.4 SD (N-50), and students with learning disability and attention deficit disorder, mean age 8.7, 1.4 SD (N-50), were assessed. The Paediatric Early Elementary Examination and the Aggregate Neurobehavioural Student Health Education Review were administered and their scores as well as pattern of correlations within and between domains were analysed. Only few differences in neurocognitive functions between these groups were evident. Most neurocognitive domains were similarly intercorrelated in the two groups. However, recall was correlated with other neurocognitive domains only among the children with learning and attention deficits. A proportion of significant correlations between neurocognitive and behavioural domains was found among the children with learning disability and attention deficit disorder, but not among the children with learning disability only. It appears that while neurocognitive profiles are similar in these two groups, their interrelationship with behavioural patterns differ. These findings give support to the neurological origin of attention deficit disorder related behaviours among learning disabled children. Different interventions should therefore be considered for each of these entities.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

Obstetric complications and transition to psychosis in an "ultra" high risk sample.

OBJECTIVE: An association between birth and pregnancy complications and the later development of schizophrenia has been described for decades and obstetric complications (OCs) have been proposed as a vulnerability marker for psychosis in line with the neurodevelopmental hypothesis of psychotic disorders. Previous studies of OCs have focused on established schizophrenia. In this study, the association between OCs and the development of psychotic disorder was studied in a group of 74 young people identified as being at very high risk for the first onset of psychosis. METHOD: The "ultra" high risk (UHR) cohort was identified by the presence of subthreshold psychotic symptoms, or a combination of first-degree relative with a psychotic disorder and recent functional decline. Thirty-eight per cent of the cohort developed an acute psychotic episode over the 12-month period after recruitment. As a component of a larger research study, the level of OCs experienced by the UHR cohort was assessed at intake. RESULTS: Obstetric complications were not associated with the later development of psychosis in the UHR group included in this study. CONCLUSIONS: This study does not support a role for OCs as a risk factor for the later development of psychosis; however, we cannot conclude that they should be completely ignored as a candidate risk factor for onset of psychosis. A number of weaknesses of the study suggest that it may be premature to dismiss OCs as a risk factor for the development of psychosis and further research is urged in this area.

Acute Disease↗

PubMed2001

Challenges, status, and opportunities for studying developmental neuropathology in adult schizophrenia.

Neurodevelopmental theories of the pathoetiology of schizophrenia have been at the forefront of schizophrenia research in recent years. Support for these theories is substantial and growing. Epidemiological, phenomenological, and clinical neurobiological research have provided compelling though still circumstantial evidence. Neuropathological investigations also have provided some evidence; however, these have yet to actualize their potential for revealing the cellular and molecular nature of developmental aberrancies in this disease. This article summarizes the clinical evidence suggesting abnormal neurodevelopment in schizophrenia, outlines some of the important anatomic, cellular, and molecular mechanisms of normal central nervous system development, reviews current neuropathological findings relevant to neurodevelopment in schizophrenia, and suggests some new directions and opportunities for discovering the molecular neurodevelopmental basis of the disorder.

Atrophy↗

PubMed1989

Social class, marriage, and fertility in schizophrenia.

The hypothesis is presented that the etiology of schizophrenia is neurodevelopmental: schizophrenia is a disorder occurring in extremely late maturers, whereas manic-depressive psychosis affects early maturers. This hypothesis is related to recent neurobiological findings and also to the following epidemiological and demographic topics covered by the author in her review of social class, marriage, and fertility in schizophrenia: Kretschmer's observations of body type differences between patients with schizophrenia and manic-depressive psychosis; trends in the incidence of schizophrenia and manic-depressive psychosis in industrialized versus developing economies; changing epidemiology of the subtypes of schizophrenia and of manic-depressive psychosis; sex differences in manic-depressive psychosis and schizophrenia; fertility and childlessness in schizophrenia; selection for marriage in schizophrenia; marriage patterns, inbreeding, and schizophrenia; social class, social mobility, and occupation in schizophrenia; social mobility and social selection; excess of schizophrenia in the lowest strata of society; social class, course, and outcome; and social stress and schizophrenia.

Bipolar Disorder↗

PubMed2003

Using sex differences in psychopathology to study causal mechanisms: unifying issues and research strategies.

BACKGROUND: Although there is an extensive literature, both speculative and empirical, on postulated differences between males and females in their rates of particular types of disorder, very little is known about the mechanisms that underlie these sex differences. The study of mechanisms is important because it may provide clues on aetiological processes. The review seeks to outline what is known, what are the methodological hazards that must be dealt with, and the research strategies that may be employed. METHODS: We note the need for representative general samples, and for adequate measurement and significance testing if valid conclusions are to be drawn. We put forward three levels of causes that have to be considered: a genetically determined distal basic starting point; the varied consequences of being male or female; and the proximal risk or protective factors that are more directly implicated in the causal mechanisms that predispose to psychopathology. In delineating these, we argue that three key sets of evidential criteria have to be met: a) that the risk factors differ between males and females; b) that they provide for risk or protection within each sex; and c) that when introduced into a causal model, they eliminate or reduce the sex differences in the disorders being studied. RESULTS: A male excess mainly applies to early onset disorders that involve some kind of neurodevelopmental impairment. A female excess mainly applies to adolescent-onset emotional disorders. No variables have yet met all the necessary criteria but some good leads are available. The possible research strategies that may be employed are reviewed. CONCLUSIONS: The systematic investigation of sex differences constitutes an invaluable tool for the study of the causal processes concerned with psychopathology.

Adolescent↗

PubMed2006

Grey matter correlates of minor physical anomalies in the AeSOP first-episode psychosis study.

BACKGROUND: Minor physical anomalies are more prevalent among people with psychosis. This supports a neurodevelopmental aetiology for psychotic disorders, since these anomalies and the brain are both ectodermally derived. However, little is understood about the brain regions implicated in this association. AIMS: To examine the relationship between minor physical anomalies and grey matter structure in a sample of patients with first-episode psychosis. METHOD: Sixty patients underwent assessment of minor physical anomalies with the Lane scale. High-resolution magnetic resonance images and voxel-based methods of image analysis were used to investigate brain structure in these patients. RESULTS: The total anomalies score was associated with a grey matter reduction in the prefrontal cortex and precuneus and with a grey matter excess in the basal ganglia, thalamus and lingual gyrus. CONCLUSIONS: Minor physical anomalies in a sample of patients with first-episode psychosis are associated with regional grey matter changes. These regional changes may be important in the pathogenesis of psychotic disorder.

Adolescent↗

PubMed2026

Genomic Sequencing in Neonatal Encephalopathy and Suspected Hypoxic-Ischaemic Encephalopathy: A Systematic Review.

BACKGROUND: Neonatal encephalopathy (NE) is a major cause of neonatal mortality and long-term neurological disability. Although hypoxic-ischaemic encephalopathy (HIE) is the most common cause, several genetic disorders may mimic or coexist with hypoxic-ischaemic injury. Next-generation sequencing has emerged as a promising diagnostic tool in this setting. This systematic review evaluated the current evidence on genomic sequencing in NE. MATERIAL AND METHODS: A systematic review was conducted according to PRISMA 2020 guidelines and prospectively registered in PROSPERO. PubMed/MEDLINE, Embase, and Scopus were searched from inception to June 2026. Eligible studies included neonates (≤28 days) with NE, suspected or confirmed HIE, HIE mimics, or unexplained NE who underwent genomic sequencing. Whole-exome sequencing (WES), whole-genome sequencing (WGS), clinical exome sequencing (CES), rapid genomic sequencing, and targeted next-generation sequencing panels were considered. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Seven studies met the inclusion criteria. Considerable heterogeneity was observed regarding patient selection, sequencing strategies, and reported outcomes. Among diagnostic sequencing studies, diagnostic yield ranged from 23.5% to 53.1%. Pathogenic and likely pathogenic variants were identified in genes associated with developmental and epileptic encephalopathies, metabolic disorders, mitochondrial diseases, and neurodevelopmental syndromes, including SCN2A, KCNQ2, CACNA1A, STXBP1, PTPN11, BCOR, MMUT, COQ2, and GBE1. Genomic sequencing frequently refined or changed the initial diagnosis, improved prognostic assessment and genetic counselling, and, in selected cases, guided disease-specific treatment. One study investigated genetic susceptibility to hypoxic-ischaemic injury rather than diagnostic sequencing. CONCLUSIONS: Genomic sequencing provides clinically meaningful diagnoses in a substantial proportion of neonates with unexplained NE or atypical HIE presentations. Current evidence supports integrating genomic sequencing into the diagnostic evaluation of selected infants, although larger prospective studies are needed to define its optimal timing, clinical utility, and cost-effectiveness.

Humans↗

PubMed2006

Biological risk factors in pediatric bipolar disorder.

BACKGROUND: The current study attempted to determine whether neurodevelopmental and acquired brain abnormalities are more common in pediatric bipolar disorder (PBD). METHODS: The study sample consisted of 98 subjects with a mean age of 11.5 +/- 3.3 years comprising three demographically matched groups: healthy controls (HC, n = 28), subjects with bipolar disorder - Type I (PBD, n = 37), and bipolar disorder - Type I combined with attention deficit hyperactivity disorder (PBD+ADHD, n = 33). Family history of PBD was determined using the Family History Screen. Additional measures were administered to assess the history on perinatal risk, development milestones, serious physical illnesses, and head injury. RESULTS: Logistic regression showed that that family history and perinatal risk factors predicted the diagnosis of PBD. PBD diagnosis was 15 times higher among those with a family history of BD. Second, for every additional perinatal risk factor such as prenatal exposure to drugs or birth complications, the risk of having a PBD diagnosis increased more than six-fold. CONCLUSIONS: Having a positive familial history of BD in a first degree relative and perinatal insults may elevate the risk for developing PBD. Presence of these risk factors, especially in the context of clinical signs of affect dysregulation, should alert clinicians to screen for PBD.

Adolescent↗

PubMed2001

Neurodevelopmental risk factors in schizophrenia.

The authors review environmental and neurodevelopmental risk factors for schizophrenic disorders, with emphasis on minor physical anomalies, particularly craniofacial anomalies and dermatoglyphic variations. The high prevalence of these anomalies among schizophrenic subjects supports the neurodevelopmental theory of the etiology of schizophrenia, since they suggest either genetically or epigenetically controlled faulty embryonic development of structures of ectodermal origin like brain and skin. This may disturb neurodevelopment that in turn may cause these subjects to be at increased risk for the development of schizophrenia and related disorders. The precise confirmation of this theory, at least in some cases, will provide further understanding of these illnesses, allowing easy and inexpensive identification of subjects at risk and providing guidelines for the development of new pharmacological interventions for early treatment and even for primary prevention of the illness.

Brain Diseases↗

PubMed2001

Diagnosis and treatment of feeding disorders in children with developmental disabilities.

OBJECTIVES: To determine the results of diagnostic evaluation and the effects of nutritional intervention on energy consumption, weight gain, growth, and clinical status of children with neurodevelopmental disabilities and suspected feeding disorders. METHODS: We studied 79 children with moderate to severe motor or cognitive dysfunction (male:female, 38:41; age, 5.8 +/- 3.7 years) who were referred for diagnosis and treatment of feeding or nutritional problems. Initial assessments included a 3-day calorie intake record, videofluoroscopic swallowing study (VFSS), 24-hour intraesophageal pH monitoring, milk scintigraphy, and esophagogastroduodenoscopy. RESULTS: These studies demonstrated gastroesophageal reflux (GER) with or without aspiration in 44 of 79 patients (56%), oropharyngeal dysphagia in 21 (27%), and aversive feeding behaviors in 14 (18%). Diagnosis-specific approaches included medical GER therapy in 20 patients (25%), fundoplication plus gastrostomy tube (GT) in 18 (23%), oral supplements in 17 (22%), feeding therapy only in 14 (18%), and GT only in 10 (13%). After 24.6 +/- 3.0 months, relative calorie intake, expressed as intake (kcal/d)/recommended daily allowance (RDA, kcal/d), improved significantly (initial:final = 0.78 +/- 0.36:1.23 +/- 0.27). The z scores increased significantly for both weight (initial:final = -2.80 +/- 1.33:-0.81 +/- 0.69) and height (-3.14 +/- 0.98:-2.00 +/- 0.67). Improved subcutaneous tissue stores were demonstrated by increased thickness of both subscapular skinfolds (change = 71% +/- 26%) and triceps skinfolds (38% +/- 17%). After nutritional intervention, the acute care hospitalization rate, compared with the 2-year period before intervention, decreased from 0.4 +/- 0.18 to 0.15 +/- 0.06 admissions per patient-year and included only 3 admissions (0.02 per patient-year) related to feeding problems. CONCLUSIONS: In children with developmental disabilities, diagnosis-specific treatment of feeding disorders results in significantly improved energy consumption and nutritional status. These data also indicate that decreased morbidity (reflected by a lower acute care hospitalization rate) may be related, at least in part, to successful management of feeding problems. Our results emphasize the importance of a structured approach to these problems, and we propose a diagnostic and treatment algorithm for children with developmental disabilities and suspected feeding disorders.children, developmental disabilities, fundoplication, gastroesophageal reflux, gastrostomy, hospitalization, nutrition.

Adolescent↗

PubMed1997

Genetic factors in the etiology of child psychiatric disorders.

This review discusses recent advances in our understanding of the genetic basis of child psychiatric disorders. As in adult psychiatry, progress in this area has been slow. First, it now appears clearer than ever that the "one gene, one disease" model is inappropriate for the vast majority of psychiatric disorders. Second, considerable resources are still being devoted to the search for genes, done using linkage and association models, together with twin and adoption studies, on the basis of case recognition according to conventional disease classification. Recent progress with conventionally specified disorders is reviewed and contrasted with the remarkable advances being made in the identification of the genetic basis of key cognitive processes through the power of modern molecular genetic techniques. Child psychiatric genetic could profit from a new focus on the search for the genetic processes underlying specific cognitive functions that, in turn, underpin child psychiatric disorders, especially those that are neurodevelopmental in origin.

Biological Psychiatry↗

PubMed1992

Child and adolescent (early onset) schizophrenia: a review in light of DSM-III-R.

Early onset schizophrenia (EOS) is defined as that beginning in childhood or adolescence (under 16 or 17). Studies of EOS are infrequent, and comparative adult figures not always available, but tentative conclusions may be drawn. EOS is more common in males; symptomatology is often undifferentiated; frequencies of homotypic family disorder, premorbid schizotypal personality, and neurodevelopmental abnormalities high; outcome poor but only slightly worse than in adults; response to psychotropic drug treatment probably similar though not properly tested; and confusion with psychotic bipolar disorder particularly common. Onset before language is developed presents special diagnostic difficulties. There are a few reports of autistic children developing schizophrenia but this requires replication. Differences from adult schizophrenia are more marked when onset is in childhood than in adolescence but all are quantitative rather than qualitative suggesting that the disorders are the same and that there should be no separate category for children or adolescents.

Adolescent↗

PubMed1997

Developmental insanity or dementia praecox: was the wrong concept adopted?

Over a century ago, the Scottish psychiatrist Thomas Clouston proposed the idea of a developmental or adolescent insanity. He characterised the condition as having a male predominance and a poor outcome, and noted the frequency of a family history and of minor anomalies of the palate; he considered it a disorder of cortical development and the onset of psychotic symptoms due to maturation during adolescence "of certain parts of the brain which had lain dormant before". Clouston's idea was subsequently eclipsed by the broader dementia-praecox espoused by Kraepelin and Bleuler, but recent epidemiological, neuroimaging, and neuropathological research supports the existence, within the schizophrenia syndrome of a group of patients with a severe, early onset, developmental psychosis. This disorder, re-christened as neurodevelopmental schizophrenia, is associated with childhood language and speech difficulties which render subjects more likely to later misinterpret their own inner speech as external voices; like all developmental disorders of language, it is commoner in males. Predisposing factors include the inheritance of abnormal cerebral asymmetry, and early environmental hazards of brain development such as prenatal exposure to maternal viral infection and perinatal complications.

Adolescent↗

PubMed2002

Neurodevelopmental liabilities in alcohol dependence: central serotonin and dopamine dysfunction.

Alcoholism is a complex disorder with symptoms ranging from abuse to dependence, often comorbid with depression, antisocial personality, or anxiety. Neurodevelopmental causes of the disorder are unknown but inferences are possible from current knowledge. Neurobiological studies implicate multiple brain changes, which may be characterized as premorbid or morbid. These studies have also examined specific aspects of the alcohol dependence syndrome, including alcohol reinforcement and craving. Here, we review the evidence for vulnerability factors in alcohol dependence, with an emphasis on central serotonin (5-HT) and dopamine (DA). Serotonin dysfunction likely contributes to the development of alcoholism since studies of alcohol-preferring rodents show decreased 5-HT function on many measures. We have shown that serotonin-enhancing drugs reduce consumption and craving in mild to moderate alcoholics, yet similar studies in severely dependent individuals remain inconclusive. Studies indicate that serotonin dysfunction may contribute to the development of dependence via impaired impulse control and/or mood regulation. The mesocorticolimbic dopamine pathway represents another important pathophysiological target in alcoholism. Differences in D(2) receptor density, dopamine sensitivity, and gene expression have been linked to consumption, reinforcement, craving, and relapse. However, while DA agonists reduce self-administration in animals, we found no effect in humans with long-acting bromocriptine, a D(2) agonist. Dopamine may contribute differentially to the development of dependence via its effects on alcohol wanting, reinforcement, and reward memory. Although animal experiments show consistent roles for serotonin and dopamine in alcohol dependence, human studies are not always concordant. Such discrepancies highlight the complexity of dependence-related behaviors in humans and of identifying vulnerabilities to alcoholism.

Journal Article↗

PubMed2005

Genetics of congenital hypothyroidism.

Congenital hypothyroidism is the most common neonatal metabolic disorder and results in severe neurodevelopmental impairment and infertility if untreated. Congenital hypothyroidism is usually sporadic but up to 2% of thyroid dysgenesis is familial, and congenital hypothyroidism caused by organification defects is often recessively inherited. The candidate genes associated with this genetically heterogeneous disorder form two main groups: those causing thyroid gland dysgenesis and those causing dyshormonogenesis. Genes associated with thyroid gland dysgenesis include the TSH receptor in non-syndromic congenital hypothyroidism, and Gsalpha and the thyroid transcription factors (TTF-1, TTF-2, and Pax-8), associated with different complex syndromes that include congenital hypothyroidism. Among those causing dyshormonogenesis, the thyroid peroxidase and thyroglobulin genes were initially described, and more recently PDS (Pendred syndrome), NIS (sodium iodide symporter), and THOX2 (thyroid oxidase 2) gene defects. There is also early evidence for a third group of congenital hypothyroid conditions associated with iodothyronine transporter defects associated with severe neurological sequelae. This review focuses on the genetic aspects of primary congenital hypothyroidism.

Amino Acid Sequence↗