Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mapping of nicotinic acetylcholine receptor (nAChR) subtypes and subunits in human brain is far from complete, however it is clear that multiple subunits are present (including alpha3, alpha4, alpha5, alpha6 and alpha7, beta2, alpha3 and beta4) and that these receptors are not solely distributed on neurones, but also on cerebral vasculature and astrocytes. It is important to elucidate subunit composition of receptors associated with different cell types and pathways within the human CNS in terms of potential nicotinic therapy for a range of both developmental and age-related disorders in which nAChR attenuation occurs. Reductions in nAChRs are reported in Alzheimer's and Parkinson's diseases, dementia with Lewy bodies, schizophrenia and autism, but may not be associated with reduced cortical cholinergic innervation observed in vascular dementia or occur at an early stage in Down's syndrome. Changes in nAChR expression in neuropsychiatric disorders appear to be brain region and subtype specific and have been shown in some instances to be associated with pathology and symptomatology. It is likely that deficits in alpha4-containing receptors predominate in cortical areas in Alzheimer's disease and autism, whereas reduction of alpha7 receptors may be more important in schizophrenia. Changes in astrocytic and vascular nAChR expression in neurodegenerative diseases should also be considered. Studies using both animal models and human autopsy tissue suggest that nAChRs can play a role in neuroprotection against age-related pathology. It is possible that the development of nAChR subtype specific drugs may lead to advances in therapy for both age-related and psychiatric disorders.
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PMID:Human brain nicotinic receptors, their distribution and participation in neuropsychiatric disorders. 1276 11

Autism has been becoming the focus of attention as its apparently increasing prevalence is better appreciated. According to some estimates, the frequency of children with autistic spectrum disorder (ASD) can be as high as 1 in 150. The diagnosis can be made as early as 2 years of age, and autistic patients often have a normal life span. Thus, in terms of the number of "patient years," ASD represents a market that is as large as that of the biggest neurological indication, Alzheimer's disease. Despite the clear unmet medical need, no effective treatment is available. This may be because the mechanism of ASD is not understood. The aim of the present paper is to review recent advances in autism research and to discuss some of the most stressing problems mainly from a preclinical research standpoint. We hope to draw attention to the need to study this devastating disease that places an enormous burden on the society in general and the relatives and caregivers of autistic patients in particular.
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PMID:Autism: a large unmet medical need and a complex research problem. 1295 40

Australian research in psychiatric genetics covers molecular genetic studies of depression, anxiety, alcohol dependence, Alzheimer's disease, bipolar disorder, schizophrenia, autism, and attention deficit hyperactivity disorder. For each disorder, a variety of clinical cohorts have been recruited including affected sib pair families, trios, case/controls, and twins from a large population-based twin registry. These studies are taking place both independently and in collaboration with international groups. Microarray studies now complement DNA investigations, while animal models are in development. An Australian government genome facility provides a high throughput genotyping and mutation detection service to the Australian scientific community, enhancing the contribution of Australian psychiatric genetics groups to gene discovery.
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PMID:Psychiatric genetics in Australia. 1296 Jul 44

The National Institutes of Health (NIH) is amending its regulations governing center grants to reflect their applicability to several new grant programs, including research on autism, Alzheimer's disease, fragile X disease, and minority health disparities and other types of health disparities.
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PMID:National Institutes of Health Center Grants. Final rule. 1467 96

Autism is reaching epidemic proportions. The diagnosis can be made as early as 2 years of age, and autistic patients are expected to have a normal life span. Thus, in terms of the number of 'patient years', autism spectrum disorder (ASD) represents a market that is as large as that of the biggest neurological indication, Alzheimer's disease. However, despite the clear unmet medical need no effective treatment is yet available. This could be because the biology of ASD is not clearly understood and thus proper drug treatment has not been possible. However, significant advances are being made toward understanding the mechanisms of the disease. Here, we review the most recent preclinical advances in the hope that they will lead to a breakthrough in the near future.
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PMID:Autism: a target of pharmacotherapies? 1514 20

In recent years, VIP/PACAP/secretin family has special interest. Family members are vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), secretin, glucagon, glucagon like peptide-1 (GLP(1)), GLP(2), gastric inhibitory peptide (GIP), growth hormone releasing hormone (GHRH or GRF), and peptide histidine methionine (PHM). Most of the family members present both in central nervous system (CNS) and in various peripheral tissues. The family members that are released into blood from periphery, especially gut, circulate the brain and they can cross the blood brain barrier. On the other hand, some of the members of this family that present in the brain, can cross from brain to blood and reach the peripheral targets. VIP, secretin, GLP(1), and PACAP 27 are transported into the brain by transmembrane diffusion, a non-saturable mechanism. However, uptake of PACAP 38 into the brain is saturable mechanism. While there is no report for the passage of GIP, GLP(2), and PHM, there is only one report that shows, glucagon and GHRH can cross the BBB. The passage of VIP/PACAP/secretin family members opens up new horizon for understanding of CNS effects of peripherally administrated peptides. There is much hope that those peptides may prove to be useful in the treatment of serious neurological diseases such as Alzheimer's disease, amyotropic lateral sclerosis, Parkinson's disease, AIDS related neuropathy, diabetic neuropathy, autism, stroke and nerve injury. Their benefits in various pathophysiologic conditions undoubtly motivate the development of a novel drug design for future therapeutics.
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PMID:Passage of VIP/PACAP/secretin family across the blood-brain barrier: therapeutic effects. 1513 84

Magnetic resonance imaging (MRI) has opened a new window to the brain. Measuring hippocampal volume with MRI has provided important information about several neuropsychiatric disorders. We reviewed the literature and selected all English-language, human subject, data-driven papers on hippocampal volumetry, yielding a database of 423 records. Smaller hippocampal volumes have been reported in epilepsy, Alzheimer's disease, dementia, mild cognitive impairment, the aged, traumatic brain injury, cardiac arrest, Parkinson's disease, Huntington's disease, Cushing's disease, herpes simplex encephalitis, Turner's syndrome, Down's syndrome, survivors of low birth weight, schizophrenia, major depression, posttraumatic stress disorder, chronic alcoholism, borderline personality disorder, obsessive-compulsive disorder, and antisocial personality disorder. Significantly larger hippocampal volumes have been correlated with autism and children with fragile X syndrome. Preservation of hippocampal volume has been reported in congenital hyperplasia, children with fetal alcohol syndrome, anorexia nervosa, attention-deficit and hyperactivity disorder, bipolar disorder, and panic disorder. Possible mechanisms of hippocampal volume loss in neuropsychiatric disorders are discussed.
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PMID:MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. 1535 39

Brain asymmetry is understood as an anatomical, functional or neurochemical difference between the two hemispheres. It is not a static but rather a dynamic phenomenon in which both environmental and endogenous factors act as modulators. Aging modifies brain asymmetry, and an imbalance in specific asymmetries characterizes some brain disorders such as schizophrenia, depression, infantile autism or Alzheimer's disease. However, it is not clear whether these changes are a cause or a consequence of these disorders. Although this phenomenon has been extensively studied, its functional significance is not yet clear, and the neurochemical basis underlying anatomical or functional asymmetries in the brain is still poorly understood. In recent decades intensive research on the behaviour of neuropeptides has revealed asymmetries in their distribution in the brain, and there is evidence that the lateralized patterns of distribution are involved in the regulatory control of some neuropeptidase activities. Therefore, if these enzymatic activities are distributed asymmetrically, their endogenous substrates would presumably be affected in an asymmetrical way, as would the functions they are involved in. Here we review the most significant literature regarding human and animal brain asymmetry involving neuropeptides such as corticotropin-releasing hormone, cholecystokinin, luteinizing hormone-releasing hormone, thyrotropin-releasing hormone and angiotensin II, as well as their neuropeptidases.
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PMID:Neuropeptides, neuropeptidases and brain asymmetry. 1558 19

The brain is one of the organs with the highest level of lipids (fats). Brain lipids, formed of fatty acids, participate in the structure of membranes, for instance 50 % fatty acids are polyunsaturated in the gray matter, 1/3 are of the omega-3 family, and are thus of dietary origin. The omega-3 fatty acids (mainly alpha-linolenic acid, ALA) participated in one of the first experimental demonstration of the effect of dietary substances (nutrients) on the structure and function of the brain. Experiments were first of all carried out on ex vivo cultured brain cells, then on in vivo brain cells (neurons, astrocytes and oligodendrocytes) from animals fed ALA deficient diet, finally on physicochemical (membrane fluidity), biochemical, physiological, neurosensory (vision an auditory responses), and behavioural or learning parameters. These findings indicated that the nature of polyunsaturated fatty acids (in particular omega-3) present in formula milks for human infants determines to a certain extend the visual, neurological, and intellectual abilities. Thus, in view of these results and of the high polyunsaturated fatty acid content of the brain, it is normal to consider that they could be involved in psychiatric diseases and in the cognitive decline of ageing. Omega-3 fatty acids appear effective in the prevention of stress, however their role as regulator of mood is a matter for discussion. Indeed, they play a role in the prevention of some disorders including depression (especially post partum), as well as in dementia, particularly Alzheimer's disease. Their role in major depression and bipolar disorder (manic-depressive disease), only poorly documented, is not clearly demonstrated. The intervention of omega-3 in dyslexia, autism, and schizophrenia has been suggested, but it does not necessarily infer a nutritional problems. The respective importance of the vascular system (where the omega-3 are actually active) and the cerebral parenchyma itself, remain to be resolved. However, the insufficient supply of omega-3 fatty acids in today diet in occidental (less than 50 % of the recommended dietary intakes values for ALA) raises the problem of how to correct inadequate dietary habits, by prescribing mainly rapeseed (canola) and walnut oils on the one hand, fatty fish (wild, or farmed, but the nature of fatty acids present in fish flesh is the direct consequence of the nature of fats with which they have been fed), and eggs from laying hens fed omega-3 fatty acids.
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PMID:[Omega-3 fatty acids in psychiatry]. 1569 97

In view of the high omega-3 poly unsaturated fatty acid content of the brain, it is evident that these fats are involved in brain biochemistry, physiology and functioning; and thus in some neuropsychiatric diseases and in the cognitive decline of ageing. Though omega-3 fatty acids (from fatty fish in the human diet) appear effective in the prevention of stress, their role as regulator of mood and of libido is a matter for discussion pending experimental proof in animal and human models. Dietary omega-3 fatty acids play a role in the prevention of some disorders including depression, as well as in dementia, particularly Alzheimer's disease. Their direct role in major depression, bipolar disorder (manic-depressive disease) and schizophrenia is not yet established. Their deficiency can prevent the renewal of membranes, and thus accelerate cerebral ageing; none the less, the respective roles of the vascular component on one hand (where the omega-3's are active) and the cerebral parenchyma itself on the other, have not yet been clearly resolved. The role of omega-3 in certain diseases such as dyslexia and autism is suggested. In fact, omega-3 fatty acids participated in the first coherent experimental demonstration of the effect of dietary substances (nutrients) on the structure and function of the brain. Experiments were first of all carried out one x-vivo cultured brain cells (1), then on in vivo brain cells(2), finally on physiochemical, biochemical, physiological, neurosensory, and behavioural parameters (3). These findings indicated that the nature of poly unsaturated fatty acids(in particular omega-3) present in formula milks for infants (both premature and term) determines the visual, cerebral,and intellectual abilities, as described in a recent review (4). Indeed,the insufficient dietary supply of omega-3 fatty acids in today's French and occidental diet raises the problem of how to correct dietary habits so that the consumer will select foods that are genuinely rich in omega-3/ the omega-3 family ; mainly rapeseed, (canola) and walnut oils on one hand and fatty fish on the other.
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PMID:Dietary omega-3 Fatty acids and psychiatry: mood, behaviour, stress, depression, dementia and aging. 1575 Jun 63


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