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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Examined hypothalamic-pituitary-adrenal axis (HPA axis) function in 30 children with attention-deficit hyperactivity disorder (ADHD) by measuring the diurnal variation and response to the dexamethasone suppression test (DST) of saliva cortisol. Normal diurnal saliva cortisol rhythm was found in only 43.3% of the ADHD children. DST showed suppression in 46.7% of the ADHD children. An abnormal diurnal rhythm and nonsuppression to the DST were more frequent in the severely hyperactive group than in the mildly were more frequent in the severely hyperactive group than in the mildly hyperactive group of children with ADHD. These results suggest abnormalities in HPA axis function in some children with ADHD, especially those exhibiting severe hyperactivity.
J Autism Dev Disord 1993 Mar
PMID:Hypothalamic-pituitary-adrenal axis function in children with attention-deficit hyperactivity disorder. 846 2

1. This study aims (1) to determine whether secretin is synthesized centrally, specifically by the HPA axis and (2) to discuss, on the basis of the findings in this and previous studies, secretin's possible neuroregulatory role in autism. 2. An immunocytochemical technique with single-cell resolution was performed in 12 age/weight-matched male rats pretreated with stereotaxic microinjection of colchicine (0.6 microg/kg) or vehicle into the lateral ventricle. Following 2-day survival, rats were anesthetized and perfused for immunocytochemistry. Brain segments were blocked and alternate frozen 30-microm sections incubated in rabbit antibodies against secretin, vasoactive intestinal peptide, glucagon, or pituitary-adenylate-cyclase-activating peptide. Adjacent sections were processed for Nissl stain. Preadsorption studies were performed with members of the secretin peptide family to demonstrate primary antibody specificity. 3. Specificity of secretin immunoreactivity (ir) was verified by clear-cut preadsorption control data and relatively high concentrations and distinct topographic localization of secretin ir to paraventricular/supraoptic and intercalated hypothalamic nuclei. Secretin levels were upregulated by colchicine, an exemplar of homeostatic stressors, as compared with low constitutive expression in untreated rats. 4. This study provides the first direct immunocytochemical demonstration of secretinergic immunoreactivity in the forebrain and offers evidence that the hypothalamus, like the gut, is capable of synthesizing secretin. Secretin's dual expression by gut and brain secretin cells, as well as its overlapping central distribution with other stress-adaptation neurohormones, especially oxytocin, indicates that it is stress-sensitive. A neuroregulatory relationship between the peripheral and central stress response systems is suggested, as is a dual role for secretin in conditioning both of those stress-adaptation systems. Colchicine-induced upregulation of secretin indicates that secretin may be synthesized on demand in response to stress, a possible mechanism of action that may underlie secretin's role in autism.
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PMID:Secretin: hypothalamic distribution and hypothesized neuroregulatory role in autism. 1517 37

Recent human studies have shown that a wide variety of prenatal stressors, from anxiety and partner relationship problems, to natural disasters, increase the risk for a diverse range of adverse neurodevelopmental outcomes in the child. These include impaired cognitive development and behavioral problems, autism and schizophrenia. However, many questions remain about the underlying processes. Much of the research, based on animal studies, has focussed on the maternal HPA axis, with mixed results. Maternal stress or anxiety during pregnancy has been found to be weakly associated with raised maternal cortisol, if at all. The placenta may be a more promising programming vector, because it controls fetal exposure to the maternal environment. Animal studies indicate that prenatal stress can affect the activity of the placental barrier enzyme 11-betaHSD2, which metabolises cortisol. We review the evidence for a similar mechanism in humans and how maternal stress may cause other changes in the placenta which affect fetal neurodevelopment.
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PMID:Prenatal stress and neurodevelopment of the child: focus on the HPA axis and role of the placenta. 1954 65

Research that has assessed the psychophysiological consequences of caregiver stress in young and middle aged caregivers, that is, in populations not contending with age associated decline of the endocrine and immune systems, has been scarce and yielded inconsistent findings. To extend work in this area, this study assessed the psychosocial, endocrine and immune consequences of caregiver stress in a cross sectional sample of young and middle aged caregivers of children with autism and attention deficit hyperactivity disorder (ADHD) compared against parents of typically developing children. Caregivers (n=56) and parent controls (n=22) completed measures of psychological distress (perceived stress, anxiety/depression), social support and physical health complaints. To capture important indices of the diurnal cortisol pattern, cortisol was measured at waking, 30 min post waking, 1200 h and 2200 h on two consecutive weekdays. Venous blood was taken to assess systemic concentrations of proinflammatory biomarkers, interleukin-6 (IL-6) and C-reactive protein (CRP). Caregivers scored markedly higher on all measures of psychological distress; scores on social support subscales, however, were significantly lower in this group. Diurnal patterns of cortisol secretion did not differentiate between the groups; however, caregivers displayed elevated systemic concentrations of the proinflammatory biomarker, CRP and reported more frequent episodes of physical ill health. The stress of caregiving exacts a significant psychophysiological toll, that is, even in the absence of HPA dysregulation, caregivers demonstrated elevated concentrations of proinflammatory biomarkers and, therefore, might be at greater risk for diseases fostered by disinhibition of the inflammatory response.
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PMID:The psychosocial, endocrine and immune consequences of caring for a child with autism or ADHD. 2188 67

Anxiety and Autistic Disorder (AD) are both neurological conditions and both disorders share some features that make it difficult to precisely allocate specific symptoms to each disorder. HPA and SAM axis activities have been conclusively associated with anxiety, and may provide a method of validating anxiety rating scale assessments given by parents and their children with AD about those children. Data from HPA axis (salivary cortisol) and SAM axis (salivary alpha amylase) responses were collected from a sample of 32 high-functioning boys (M age=11yr) with an Autistic Disorder (AD) and were compared with the boys' and their mothers' ratings of the boys' anxiety. There was a significant difference between the self-ratings given by the boys and ratings given about them by their mothers. Further, only the boys' self-ratings of their anxiety significantly predicted the HPA axis responses and neither were significantly related to SAM axis responses. Some boys showed cortisol responses which were similar to that previously reported in children who had suffered chronic and severe anxiety arising from stressful social interactions. As well as suggesting that some boys with an AD can provide valid self-assessments of their anxiety, these data also point to the presence of very high levels of chronic HPA-axis arousal and consequent chronic anxiety in these boys.
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PMID:HPA and SAM axis responses as correlates of self- vs parental ratings of anxiety in boys with an Autistic Disorder. 2441 22

There is considerable evidence of a confound between symptoms of generalised anxiety disorder (GAD) and autism spectrum disorder (ASD) in children who have an ASD. Although there have been several attempts to describe how these two disorders overlap and interact to influence the assessment and diagnosis of children with an ASD, principally by reference to cortisol assayed from these children's saliva, the overall evidence is inconsistent. Because previous models of these relationships have focused upon cortisol and GAD to the exclusion of age, diurnal fluctuation in the HPA axis and the source of GAD data, these variables were examined in a sample of 150 young males with an ASD. Results indicated that there was a significant interaction between these variables, with the association between GAD and cortisol demonstrated for children but not for adolescents, with an interaction between the source of GAD information (self- vs parent-ratings) and whether the child's cortisol concentrations followed the expected diurnal reduction during the day. These data suggest that the validity of cortisol as a biomarker of GAD in children and adolescents with an ASD may be established for only selected subgroups of this population.
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PMID:Hypothalamus-pituitary-adrenal axis daily fluctuation, anxiety and age interact to predict cortisol concentrations in boys with an autism spectrum disorder. 2544 3

In this article an overview is given of the differential diagnosis of autism and autistic-like disorders. The diagnosis of the so-called 'Multiple Complex Developmental Disorders' (MCDD) as a distinct entity is discussed in relation to autism and schizophrenia. Biological research and the relevance of results until recently are discussed. Finally, the importance of the hypothalamic-pituitary-adrenal system (HPA system) as a model for research is proposed. Research on the flexibility of this system may contribute in understanding the ways of stress processing in disorders like autism, MCDD and schizophrenia.
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PMID:Autism and autistic-like disorders: the hypothalamic-pituita-ry-adrenal system as a model for research. 2696 61

Families of preschoolers participated in two dyadic home visits, once with mother (56 dyads) and once with father (59 dyads). Each member of the dyad provided three cortisol samples and participated in several interaction tasks that were behaviorally coded. Approximately half of the children had been diagnosed with autism spectrum disorders (ASD), whereas half were typically developing (TD). In a multilevel model, father's cortisol level at each timepoint predicted child cortisol. Father-child linkage was stronger in dyads that showed less reciprocity, in which fathers showed less sensitivity, and in which children showed less self-regulation and more withdrawal. Cortisol levels were not significantly correlated in mother-child dyads, and there was a trend toward moderation by ASD diagnosis, such that linkage was greater in TD children. Mother-child linkage was stronger in dyads that showed less behavioral coordination and less sensitivity. HPA axis linkage may be stronger in less behaviorally attuned dyads.
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PMID:HPA axis linkage in parent-child dyads: Effects of parent sex, autism spectrum diagnosis, and dyadic relationship behavior. 2860 42

Inflammatory mediators affect the brain during development. Neurodevelopmental disorders such as autism spectrum disorders, cognitive impairment, cerebral palsy, epilepsy, and schizophrenia have been linked to early life inflammation. Recent advances have shown the effects of systemic inflammation on children's neurodevelopment. We discuss the potential mechanisms by which inflammatory molecules can exert their effects on the developing brain and consider the roles of MHC class I molecules, the HPA axis, glial cells, and monoamine metabolism. Methods to prevent the effects of cytokine imbalance may lead to the development of new therapeutics for neuropsychiatric disorders. Future research should focus on identifying at-risk individuals and early effective interventions to prevent long-term neurodevelopmental disabilities.
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PMID:The Impact of Systemic Inflammation on Neurodevelopment. 3000 48

Maternal smoking of conventional or vapor cigarettes during pregnancy, a form of developmental nicotine exposure (DNE), enhances the risk of neurodevelopmental disorders such as ADHD, autism, and schizophrenia in children. Modeling the multigenerational effects of smoking during pregnancy and nursing in the first- (F1) and second- (F2) generation adolescent offspring of oral nicotine-treated female C57BL/6J mice, we have previously reported that DNE precipitates intergenerational transmission of nicotine preference, hyperactivity and impulsivity-like behaviors, altered rhythmicity of home cage activity, corticostriatal nicotinic acetylcholine receptor and dopamine transporter dysfunction, and corticostriatal global DNA methylome deficits. In aggregate, these DNE-evoked behavioral, neuropharmacological, and epigenomic anomalies mirror fundamental etiological aspects of neurodevelopmental disorders including ADHD, autism, and schizophrenia. Expanding this line of research, the current study profiled the multigenerational neurotrophic and neuroendocrine consequences of DNE. Results reveal impaired proBDNF proteolysis as indicated by proBDNF-BDNF imbalance, downregulation of the proBDNF processing enzyme furin, atypical glucocorticoid receptor (GR) activity as implied by decreased relative nuclear GR localization, and deficient basal plasma corticosterone (CORT) levels in adolescent DNE offspring and grandoffspring. Collectively, these data recapitulate the BDNF deficits and HPA axis dysregulation characteristic of neurodevelopmental disorders such as ADHD, autism, and schizophrenia as well as the children of maternal smokers. Notably, as BDNF is a quintessential mediator of neurodevelopment, our prior findings of multigenerational DNE-induced behavioral and neuropharmacological abnormalities may stem from neurodevelopmental insults conferred by the proBDNF-BDNF imbalance detected in DNE mice. Similarly, our findings of multigenerational GR hypoactivity may contribute to the increased risk-taking behaviors and aberrant circadian rhythmicity of home cage activity that we previously documented in first- and second-generation DNE mice.
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PMID:Developmental nicotine exposure elicits multigenerational disequilibria in proBDNF proteolysis and glucocorticoid signaling in the frontal cortices, striata, and hippocampi of adolescent mice. 3140 29


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