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

It is argued that further research to achieve more detailed diagnostic systems in many psychiatric disorders is unlikely to be productive without taking genetic effects into account. Even when this is done, for example when carrying out segregation analysis to determine a mode of genetic transmission, mental illnesses often pose specific problems that preclude accurate analysis. Because techniques in molecular biology and genetics have made it possible to study gene effects in human disease systematically it should now be possible to specify the genes that are involved. When this has been achieved then a diagnostic system based on genetic causation can develop. This will have the advantage of helping to pinpoint environmental factors more accurately. Specific strategies will need to be adopted to overcome uncertain modes of inheritance, incomplete or non-penetrance of disease alleles and disease heterogeneity. Highly speculative hypotheses can be put forward for a locus causing Alzheimer's disease on a portion of the long arm of chromosome 21. For autism it is plausible that there is a disease locus at or near the fragile X site on the X chromosome. A locus for manic depression has been very tentatively mapped using DNA markers to chromosome 11 and in a small proportion of families DNA markers have also shown some evidence for X linkage. Schizophrenia does not seem to be associated with any favoured loci. Candidate genes for schizophrenia include those encoding dopamine, other neurotransmitter receptors or enzymes and various neuropeptides such as enkephalin and beta endorphin.
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PMID:Candidate genes and favoured loci: strategies for molecular genetic research into schizophrenia, manic depression, autism, alcoholism and Alzheimer's disease. 355 29

A 14-year-old boy with mild mental retardation and behavioral features suggestive of the so called Asperger's syndrome is described. From the age of 8 years he has had recurrent episodes of lethargy. At the onset of puberty these episodes took on a more dramatic form and became more reminiscent of cycloid/manic-depressive psychosis. There is a family history of manic-depressive disorder. Neurobiological links with and differences from the syndrome of infantile autism were found. It is suggested that there is still too little evidence clearly to single out the entity of Asperger's syndrome from the spectrum of autistic syndromes.
J Autism Dev Disord 1985 Dec
PMID:Asperger's syndrome and recurrent psychosis--a case study. 407 13

Recently a new form of human mutation-expansion of trinucleotide repeats-has been found to cause the diseases of fragile X syndrome, spinal and bulbar muscular atrophy, myotonic dystrophy and, most recently, Huntington's disease. We review the emerging data on the genetics and neurobiology of these disorders. Three are characterized by unusual patterns of inheritance, in particular, genetic 'anticipation', in which the severity of the disorder increases and the age of onset decreases in successive generations of a pedigree. Several idiopathic neuropsychiatric disorders have features of inheritance consistent with anticipation. In bipolar affective disorder, there is evidence for both earlier age of onset and more severe illness in the second generation of a subset of unilineal pedigrees. There is also the suggestion of anticipation in some forms of schizophrenia, spinocerebellar atrophy and autism. Triplet repeats are present in additional known genes, both in coding regions and untranslated regions. Furthermore, many novel genes with triplet repeats are expressed in the human brain, and these are candidates to cause some forms of these neuropsychiatric disorders.
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PMID:Genes with triplet repeats: candidate mediators of neuropsychiatric disorders. 768 67

For some time it has been known through the results of family, twin, and adoption studies that heredity appears to play a significant causal role in many mental disorders, including schizophrenia, bipolar disorder, and other mood disorders, Alzheimer's Disease, panic disorder, obsessive compulsive disorder, autism, dyslexia, and Tourette's Syndrome. The precise patterns of inheritance of these complex disorders have not been determined, nor have the relevant genes been localized or cloned. Because the genetics are complex and because there is also clearly an environmental contribution to behavior, we expect the analysis of the genetics of mental illness to be arduous, and not quickly resolved. There are several compelling reasons to continue to focus our attention on uncovering the genetic factors for severe mental illness. Prominent among these are the implications for better treatment of mental disorders. The National Institute of Mental Health supports a wide range of studies on psychiatric genetic research.
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PMID:Psychiatric genetic research at the National Institute of Mental Health. 772 97

The recent discovery that expanding trinucleotide repeats are a form of mutation is a radical departure from the traditional genetic principles of inheritance based on the stable transmission of DNA sequences. The concept that a gene may be altered from tissue to tissue in a single individual or from one generation to the next and that it may confer increasing mutability on itself has provided some insight into the phenomenon of anticipation as manifested by increasing severity, declining age of onset, and increasing penetrance in several inherited disorders. This concept raises the question of how common this mutational mechanism may be in the causes of genetic disease. For example, expansions of trinucleotide repeats may be the underlying mechanism for other disorders that show features suggestive of anticipation such as schizophrenia, bipolar affective disorder, autism and other hereditary ataxias. Expressed genes with trinucleotide repeats have been observed in fetal and adult brains. A recent approach to identifying expanded repeats may simplify the process of finding candidate genes. It is intriguing to speculate how often observations such as intrafamilial variation and even new mutations may be due to such a mechanism. Systematic studies of families with disorders found to be associated with such repeats will be necessary. The implications in genetic counseling for prediction of postnatal outcome as well as risks of recurrence are truly staggering. Meanwhile, the immediate benefit of the knowledge of trinucleotide repeat expansions concerning the six disorders discussed will be the application of direct methods of diagnosis avoiding linkage analysis. The long-term benefits may very well be the discovery of more effective treatment modalities based on correction of the gene defects. Exciting times for human genetics appear to be at hand.
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PMID:Genetic anticipation. Expanding tandem repeats. 784 37

The two principal indications of clonidine in child psychiatry are the "attention-deficit hyperactivity disorder" (ADHD) and Tourette's disorder. In the first case (ADHD), clonidine (4 to 5 micrograms/kg/day) is efficient (25 to 50% of improvement) with minimal untoward effects. The comparison between clonidine and methylphenidate (MPH) in this disease showed different actions of these two drugs on target symptoms: MPH preferentially acts in children with major attention-deficit and moderate hyperactivity whereas clonidine is more advocated in ADHD children with hyperarousal, hyperactivity and aggressivity symptoms. In Tourette's disorder, clonidine improves 30-50% of cases. Many studies have compared the efficiency of clonidine, neuroleptics and clonazepam. Clonidine is less efficient than neuroleptics such as haloperidol or fluphenazine but it is more efficient than clonazepam. Clonidine seems to be a good alternative to neuroleptics when these are not tolerated. Some authors recommend the association clonidine-clonazepam. Clonidine is very useful in Tourette's disorder associated with other syndromes such as obsessive-compulsive disorder, ADHD or withdrawal symptoms of neuroleptics. In contrast, clonidine has to be avoided in a depressive child. Clonidine in other psychiatric disorders such as infantile psychosis with hyperactivity, bipolar disorder, panic disorder, aggressivity and post-traumatic stress disorder has not been studied in children, but could be worth investigating.
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PMID:[Indications for clonidine in child psychiatry]. 827 1

The two most consistent features of the diseases caused by trinucleotide repeat expansion-neuropsychiatric symptoms and the phenomenon of genetic anticipation-may be present in forms of dementia, hereditary ataxia, Parkinsonism, bipolar affective disorder, schizophrenia and autism. To identify candidate genes for these disorders, we have screened human brain cDNA libraries for the presence of gene fragments containing polymorphic trinucleotide repeats. Here we report the cDNA cloning of CAGR1, originally detected in a retinal cDNA library. The 2743 bp cDNA contains a 1077 bp open reading frame encoding 359 amino acids. This amino acid sequence is homologous (56% amino acid identify and 81% amino acid conservation) to the Caenorhabditis elegans cell fate-determining protein mab-21. CAGR1 is expressed in several human tissues, most prominently in the cerebellum, as a message of approximately 3.0 kb. The gene was mapped to 13q13, just telomeric to D13S220. A 5'-untranslated CAG trinucleotide repeat is highly polymorphic, with repeat length ranging from six to 31 triplets and a heterozygosity of 87-88% in 684 chromosomes from several human populations. One allele from an individual with an atypical movement disorder and bipolar affective disorder type II contains 46 triplets, 15 triplets longer than any other allele detected. Though insufficient data are available to link the long repeat to this clinical phenotype, an expansion mutation of the CAGR1 repeat can be considered a candidate for the etiology of disorders with anticipation or developmental abnormalities, and particularly any such disorders linked to chromosome 13.
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PMID:cDNA cloning of a human homologue of the Caenorhabditis elegans cell fate-determining gene mab-21: expression, chromosomal localization and analysis of a highly polymorphic (CAG)n trinucleotide repeat. 873 27

Twelve diseases, most with neuropsychiatric features, arise from trinucleotide repeat expansion mutations. Expansion mutations may also cause a number of other disorders, including several additional forms of spinocerebellar ataxia, bipolar affective disorder, schizophrenia, and autism. To obtain candiate genes for these disorders, cDNA libraries from adult and fetal human brain were screened at high stringency for clones containing CAG repeats. Nineteen cDNAs were isolated and mapped to chromosomes 1, 2, 4, 6, 7, 8, 9, 12, 16, 19, 20, and X. The clones contain between 4 and 17 consecutive CAG, CTG, TCG, or GCA triplets. Clone H44 encodes 40 consecutive glutamines, more than any other entry in the nonredundant GenBank protein database and well within the range that causes neuronal degeneration in several of the glutamine expansion diseases. Eight cDNAs encode 15 or more consecutive glutamine residues, suggesting that the gene products may function as transcription factors, with a potential role in the regulation of neurodevelopment or neuroplasticity. In particular, the conceptual translation of clone CTG3a contains 18 consecutive glutamines and is 45% identical to the C-terminal 306 residues of the mouse numb gene product. These genes are therefore candidates for diseases featuring anticipation, neurodegeneration, or abnormalities of neurodevelopment.
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PMID:cDNAs with long CAG trinucleotide repeats from human brain. 922 80

More than 250 studies, covering 29 Northern and five Southern Hemisphere countries, have been published on the birth seasonality of individuals who develop schizophrenia and/or bipolar disorder. Despite methodological problems, the studies are remarkably consistent in showing a 5-8% winter-spring excess of births for both schizophrenia and mania/bipolar disorder. This seasonal birth excess is also found in schizoaffective disorder (December-March), major depression (March-May), and autism (March) but not in other psychiatric conditions with the possible exceptions of eating disorders and antisocial personality disorder. The seasonal birth pattern also may shift over time. Attempts to correlate the seasonal birth excess with specific features of schizophrenia suggest that winter-spring births are probably related to urban births and to a negative family history. Possible correlations include lesser severity of illness and neurophysiological measures. There appears to be no correlation with gender, social class, race, measurable pregnancy and birth complications, clinical subtypes, or neurological, neuropsychological, or neuroimaging measures. Virtually no correlation studies have been done for bipolar disorder. Regarding the cause of the birth seasonality, statistical artifact and parental procreational habits are unlikely explanations. Seasonal effects of genes, subtle pregnancy and birth complications, light and internal chemistry, toxins, nutrition, temperature/weather, and infectious agents or a combination of these are all viable possibilities.
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PMID:Seasonality of births in schizophrenia and bipolar disorder: a review of the literature. 942 62

Open clinical treatment with risperidone was administered to a clinically heterogeneous group of 11 children and adolescents (age range 5.5-16 years, mean 9.8 years) with concurrent presentation of affective symptoms (mostly suggestive of bipolar disorder), aggressive and violent behavior, and marked management problems. These patients had responded inadequately to several mood-stabilizing medications. In this outpatient sample, 8 of 11 children (73%) appeared to have therapeutic responses to risperidone. Risperidone doses were low (0.75-2.5 mg daily) and clinical responses were observed at times within days of receiving the medication. Improvement was clinically judged to be moderate to marked in 7 of 8 children. In addition, the treatment of 2 children was stopped because of drowsiness; one also experienced a weight gain of 6 kg (13 lbs). An additional child with autism and aggressive behavior who lacked affective symptoms did not respond to risperidone. None of the children showed behavioral deterioration. Seven of the 8 responders were taking concurrent medications; including 4 on mood-stabilizing medications (either lithium, carbamazepine, or valproic acid) in subtherapeutic doses. Even in combination with other medications, side effects at these doses were minimal and limited to mild sedation and, at times, troubling weight gain. Pending controlled studies, these preliminary findings suggest that risperidone--alone or in combination with mood stabilizers--may be of value in treating children and adolescents with mood disorders (especially subthreshold bipolar disorder) and aggressive behavior.
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PMID:Risperidone for young children with mood disorders and aggressive behavior. 963 79


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