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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Comparison of the properties of blood platelets and serotonergic synaptosomes suggests that the human platelet can serve as an appropriate model for the transport, metabolism, and release of serotonin (5-HT) by CNS serotonergic neurons. The study of blood 5-HT levels and platelet 5-HT pharmacodynamics in patients with a variety of psychiatric and neurologic disorders has generated interesting leads into possible abnormalities of CNS 5-HT neurons in these patients. This article reviews the experimental evidence, which uses the human platelet model to investigate neurotransmitter-related abnormalities in Down syndrome, mental retardation, infantile autism, hyperactivity syndromes (minimal brain dysfunction), schizophrenia, affective disorders, Duchenne muscular dystrophy, Parkinson disease, Huntington chorea, and migraine headaches.
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PMID:The human platelet. A diagnostic and research tool for the study of biogenic amines in psychiatric and neurologic disorders. 14 Jun 32

An open trial of pharmacological treatment with fluoxetine, ranging from 20 mg every other day to 80 mg per day, led to a significant improvement in Clinical Global Impressions ratings of Clinical Severity in 15 of 23 subjects with autistic disorder and 10 of 16 subjects with mental retardation. Six of 23 patients with autistic disorder and 3 of 16 patients with mental retardation had side effects which significantly interfered with function, consisting predominantly of restlessness, hyperactivity, agitation, decreased appetite, or insomnia. Double-blind studies of the efficacy of pharmacological agents that potently inhibit 5-HT uptake in the treatment of mental retardation coexisting with Axis I psychiatric disorders (especially obsessive-compulsive disorder) and autistic disorder are warranted.
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PMID:Fluoxetine treatment of children and adults with autistic disorder and mental retardation. 164 39

We measured platelet 3H-imipramine binding parameters in 16 subjects affected by different types of mental deficiency, all characterized by hyperactive and/or aggressive behaviour, and in 16 healthy controls. The patients had a lower maximum binding capacity than the controls, with no difference in Kd, irrespectively of the type of mental disorder. These findings suggest a link between 5-HT disturbances, reflected by reduced imipramine binding sites, and behavioural dyscontrol, expressed as hyperactivity and aggression.
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PMID:Aggression, hyperactivity and platelet imipramine binding. 165 17

The efficacy of the serotonin (5-HT) uptake inhibitor clomipramine in the treatment of self-injurious behavior (SIB) was tested in individuals with severe and profound mental retardation. Six of the 8 subjects who completed a double-blind, placebo-controlled crossover trial exhibited a clinically significant improvement (50% or greater reduction from placebo) in the frequency of SIB. Clomipramine treatment was also associated with improvement in SIB intensity, frequency of stereotypy and compulsions, teacher ratings of stereotypy and social withdrawal, and frequency of staff intervention required for problem behaviors. Adverse effects (seizure and tachycardia/agitation) occurred in 2 of the 8 subjects. These results represent the first controlled trial of a 5-HT uptake inhibitor in the treatment of SIB in mental retardation.
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PMID:Clomipramine treatment for self-injurious behavior of individuals with mental retardation: a double-blind comparison with placebo. 873 78

Platelet 3H-imipramine (3H-IMI) binding and platelet sulfotransferase (ST) activity, taken as markers of the serotonin (5-HT) and sulfated neurotransmitters (tyramine, dopamine, serotonin, noradrenaline), respectively, were evaluated in 14 severely aggressive subjects institutionalized since childhood for mental retardation and in an equal number of healthy controls. The results showed the presence of a lower number of 3H-IMI binding sites and a higher ST activity in the patients as compared with controls. These data provide supporting evidence for the hypothesis of an abnormality of the 5-HT system and suggest possible dysfunctions of dopamine and sulfated amines in aggressive behavior, at least as reflected by platelet markers.
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PMID:Platelet abnormalities in aggressive subjects with mental deficiency. 882 Jan 76

Aspartate (ASP), glutamate (GLU), noradrenaline (NA), dopamine (DA) and its acidic metabolites DOPAC and HVA, serotonin (5-HT) and its metabolite 5-HIAA were simultaneously investigated in post-mortem tissue samples from right parahippocampal gyrus (temporal cortex) and frontal cortical pole (frontal cortex) of adults with Down syndrome (DS), and of neurologically healthy controls by use of high performance liquid chromatography (HPLC). In parahippocampal gyrus, ASP, GLU, NA, DOPAC and 5-HT levels were significantly decreased in patients with DS, compared to levels found in control subjects (approximately 50%). No significant changes were observed in frontal pole. ASP and GLU levels were significantly lower in parahippocampal gyrus than in frontal pole of DS, a regional distribution that could not be observed in control subjects. In conclusion, the results of this study suggest that the temporal cortex would be more affected than the frontal cortex in adult patients with DS, a finding in line with reports showing a marked hypometabolism and extensive cell loss in temporal cortex of DS, and with those showing that parahippocampal gyrus abnormality may correlate with the extent of mental retardation affecting this type of patients.
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PMID:Excitatory amino acids and monoamines in parahippocampal gyrus and frontal cortical pole of adults with Down syndrome. 909 40

Down syndrome (DS) is a genetic disease with developmental brain abnormalities resulting in early mental retardation and precocious, age dependent Alzheimer-type neurodegeneration. Furthermore, non-cognitive symptoms may be a cardinal feature of functional decline in adults with DS. As the serotonergic system plays a well known role in integrating emotion, cognition and motor function, serotonin (5-HT) and its main metabolite, 5-hydroxyindol-3-acetic acid (5-HIAA) were investigated in post-mortem tissue samples from temporal cortex, thalamus, caudate nucleus, occipital cortex and cerebellum of adult patients with DS, Alzheimer's disease (AD) and controls by use of high performance liquid chromatography (HPLC). In DS, 5-HT was found to be age-dependent significantly decreased in caudate nucleus by 60% (DS: mean +/- SD 58.6 +/- 28.2 vs. Co: 151.7 +/- 58.4 pmol/g wet tissue weight) and in temporal cortex by about 40% (196.8 +/- 108.5 vs. 352.5 +/- 183.0 pmol/g), insignificantly reduced in the thalamus, comparable to controls in cerebellum, whereas occipital cortex showed increased levels (204.5 +/- 138.0 vs. 82.1 +/- 39.1 pmol/g). In all regions of DS samples, alterations of 5-HT were paralleled by levels of 5-HIAA, reaching significance compared to controls in thalamus and caudate nucleus. In AD, 5-HT was insignificantly reduced in temporal cortex and thalamus, unchanged in cerebellum, but significantly elevated in caudate nucleus (414.3 +/- 273.7 vs. 151.7 +/- 58.4 pmol/g) and occipital cortex (146.5 +/- 76.1 vs. 82.1 +/- 39.1 pmol/g). The results of this study confirm and extend putatively specific 5-HT dysfunction in basal ganglia (caudate nucleus) of adult DS, which is not present in AD. These findings may be relevant to the pathogenesis and treatment of cognitive and non-cognitive (behavioral) features in DS.
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PMID:Serotonin (5-HT) in brains of adult patients with Down syndrome. 1066 78

As shown in the first part of this review, well equilibrated neurotransmission in which 5-HT plays a dominant role is important for proper neuromodulation and adjustment of neuronal network elements. Adequate 5-HT system function supports regulation of intercommunicative neuronal transmission in the brain, which optimizes behavioral neuromodulation during and after different forms of exertions, thereby preventing transient dysregulation. Impairment of neuromodulation and neuronal network in the brain with transient dysfunctions or permanent substantial deficits at manifestation of various types of depression results from prevalent impairment of 5-HT neurotransmission and its central interaction with other neurotransmitter systems. Exercise-induced increase of free tryptophan (TRP) in blood occurs due to liberation from albumin, which is caused by adrenergically induced lipolysis of free fatty acids and results in higher free TRP uptake into the brain. Consecutively enhanced serotonin (5-HT) biosynthesis does not per se initiate mood impairment or central fatigue. It is suggested that in overtrained athletes central fatigue, mental deficiency and behavioral alterations with depressive mood are probably not primarily caused by metabolic and neuromuscular alterations. The primary trigger of these transient behavioural alterations might instead be initiated by a central exhaustive exercise stress which elicits impairment of complex neuromodulation, also afflicting the interaction of central neurotransmitters or hypothalamic neuropeptides and releasing factors. In a consecutive correction of the variation, the implication of the serotonergic system on the central neuromodular disturbance might improve or prevent the progressive course both in transient and in permanent mental disorders. However, an unsuccessful attempt to improve the depressive symptomatology leads mostly to an overproportional exaggeration of the behavioral changes.
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PMID:Physiology and pathophysiology of the serotonergic system and its implications on mental and physical performance. Part II. 1159 Apr 75

The Smith-Lemli-Opitz syndrome (SLOS) is a malformation/mental retardation syndrome resulting from an inborn error in 3beta-hydroxysteroid Delta7-reductase (DHCR7), the terminal enzyme required for cholesterol biosynthesis. Using a targeting strategy designed to virtually eliminate Dhcr7 activity, we have created a SLOS mouse model that exhibits commissural deficiencies, hippocampal abnormalities, and hypermorphic development of serotonin (5-HT) neurons. The latter is of particular interest with respect to current evidence that serotonin plays a significant role in autism spectrum disorders and the recent clinical observation that 50% of SLOS patients present with autistic behavior. Immunohistochemical analyses have revealed a 306% increase in the area of 5-HT immunoreactivity (5-HT IR) in the hindbrains of mutant (Dhcr7-/-) mice as compared to age-matched wild type animals. Amount of 5-HT IR was measured as total area of IR per histological section. Additionally, a regional increase as high as 15-fold was observed for the most lateral sagittal hindbrain sections. In Dhcr7-/- mice, an expansion of 5-HT IR into the ventricular zone and floor plate region was observed. In addition, the rostral and caudal raphe groups exhibited a radial expansion in Dhcr7-/- mice, with 5-HT IR cells present in locations not seen in wild type mice. This increase in 5-HT IR appears to represent an increase in total number of 5-HT neurons and fibers. These observations may help explain the behavioral phenotype seen in SLOS, and provide clues for future therapeutic interventions that utilize pharmacological modulation of the serotonergic system.
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PMID:Abnormal serotonergic development in a mouse model for the Smith-Lemli-Opitz syndrome: implications for autism. 1465 96

Autonomic dysfunction is prevalent in girls with Rett syndrome, an X-chromosome-linked disorder of mental retardation resulting from mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). This gene plays a role in regulating neuronal activity-dependent gene expression, including brain-derived neurotrophic factor (BDNF), which is a potent serotonergic (5-HT) neuronal growth factor. We analyzed selected parameters of the 5-HT system of the medulla in autopsied patients with Rett syndrome because of the role of BDNF in 5-HT cell development and because 5-HT plays a key role in modulating autonomic control. 5-HT neurons were identified by immunostaining for tryptophan hydroxylase, the biosynthetic enzyme for 5-HT. We quantitated the number of 5-HT cells in the medulla at 2 standardized levels in 11 Rett and 7 control cases. There was no significant difference in 5-HT cell number between the groups. We analyzed binding to the serotonin transporter (SERT) using the radioligand [(125)I]-RTI-55 with tissue autoradiography in 7 Rett and 5 controls in 9 cardiorespiratory-related nuclei. In the dorsal motor nucleus of the vagus (DMX) (preganglionic parasympathetic outflow), SERT binding for the control cases decreased significantly over time (p = 0.049) but did not change in the Rett cases (p = 0.513). Adjusting for age, binding between the Rett and control cases differed significantly in this nucleus (p = 0.022). There was a marginally significant age versus diagnosis interaction (p = 0.06). Thus, altered 5-HT innervation and/or uptake in the DMX may contribute to abnormal 5-HT modulation of this major autonomic nucleus in patients with Rett syndrome. These data suggest hypotheses concerning 5-HT modulation of vagal function for testing in MeCP2 knockout mice to understand mechanisms underlying autonomic dysfunction in patients with Rett syndrome.
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PMID:Serotonin transporter abnormality in the dorsal motor nucleus of the vagus in Rett syndrome: potential implications for clinical autonomic dysfunction. 1625 96


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