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

The comparable efficacy and improved safety of the atypical antipsychotics compared with the traditional antipsychotic agents in the treatment of schizophrenia and other disorders in adults have prompted the use of these agents in children and adolescents. The atypical antipsychotics are increasingly being used in children and adolescents with a variety of different psychiatric diagnoses, including schizophrenia, bipolar disorder, autism/pervasive developmental disorders, conduct disorder, depression, anxiety disorders, tic disorders, delirium, and eating disorders. Unfortunately, clinical use of these agents in pediatric patients has far exceeded the limited evidence from randomized controlled trials. This article reviews the available evidence from the published literature on the use of the atypical antipsychotics in children and adolescents with schizophrenia, bipolar disorder, and maladaptive aggression associated with autism/pervasive developmental disorders and conduct disorder/disruptive behavior disorders.
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PMID:Use of antipsychotics in children and adolescents. 1612 39

A substantial contribution of genetic factors to the risk of psychiatric disorders such as schizophrenia, bipolar disorder, autism, and drug and alcohol dependence has already been established. However, the familial transmission of these disorders cannot be explained by simple Mendelian models of inheritance, and non-genetic factors must also play a substantial role in their etiologies. Furthermore, the prevalence of any major psychiatric disorder is a great deal higher than that of Mendelian disorders. It has been suggested that evolutionary forces would rapidly eliminate large gene effects, which would suggest that mental disorders, which are highly prevalent, are associated with minor gene effects (Risch, 1994). The current paradigm is that genes with small interacting genetic effects, in conjunction with environmental factors, affect the risk for psychiatric disease. New laboratory and statistical methodology and database tools, and the availability of large clinical samples for the study of linkage and association sustain optimism that genes involved with these diseases will be characterized in the near future. This accomplishment should in turn lead not only to a better understanding of the primary molecular pathophysiology and to more specific and effective therapies, but also to a better understanding of non-genetic risk factors that could be targets for preventive strategies.
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PMID:Complexities in psychiatric genetics. 1619 61

Autism is a neurodevelopmental disorder characterized by impairment in three core symptom domains: socialization, communication, and repetitive/stereotyped behaviours. Other associated symptom domains are also affected including impulsivity/aggression, self-injury, anxiety, and mood lability. Divalproex has been shown to have efficacy in treating epilepsy, bipolar disorder, mood lability, and impulsive aggression. The present study evaluated the use of divalproex in the treatment of repetitive, compulsive-like symptoms of autism spectrum disorder (ASD). Thirteen individuals with ASD participated in an 8-wk, double-blind, placebo-controlled trial of divalproex sodium vs. placebo. There was a significant group difference on improvement in repetitive behaviours as measured by the Children's Yale-Brown Obsessive Compulsive Scale (C-YBOCS) (p=0.037) and a large effect size (d=1.616). This study provides preliminary support for the use of divalproex in treating repetitive behaviours in ASD. Further research is needed to evaluate the specificity and mechanism of action of these findings.
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PMID:Divalproex sodium vs. placebo in the treatment of repetitive behaviours in autism spectrum disorder. 1631 86

In the last 10 years, the National Institute of Mental Health has funded a number of multisite clinical trials in pediatric psychopharmacology. Trials have been completed or are in progress in attention-deficit hyperactivity disorder, depression, autism, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and other anxiety disorders. Direct comparison between different treatment modalities, such as pharmacotherapy and psychotherapy, alone or in combination, has been the focus of a number of these studies, to inform clinicians and families of the relative therapeutic benefits of alternative interventions. This article presents a brief overview of these studies.
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PMID:An update on publicly funded multisite trials in pediatric psychopharmacology. 1632 23

Synaptogenesis, the formation of functional synapses, is a crucial step for the development of the central nervous system. Among the genes involved in this process are cell adhesion molecules, such as protocadherins and neuroligins, which are essential factors for the identification of the appropriate partner cell and the formation of synapses. In this work, we studied the expression and the genetic variability of two closely related members of the protocadherin family PCDH11X/Y, located on the X and the Y chromosome, respectively. PCDH11Y is one of the rare genes specific to the hominoid lineage, being absent in other primates. Expression analysis indicated that transcripts of the PCDH11X/Y genes are mainly detected in the cortex of the human brain. Mutation screening of 30 individuals with autism identified two PCDH11Y polymorphic amino acid changes, F885V and K980N. These variations are in complete association, appeared during human evolution approximately 40,000 years ago and represent informative polymorphisms to study Y chromosome variability in populations. We studied the frequency of these variants in males with autism spectrum disorders (n = 110), attention deficit hyperactivity disorder (ADHD; n = 61), bipolar disorder (n = 61), obsessive-compulsive disorder (n = 51), or schizophrenia (n = 61) and observed no significant differences when compared to ethnically-matched control populations. These findings do not support the role of PCDH11Y, or more generally of a frequent specific Y chromosome, in the susceptibility to these neuropsychiatric disorders.
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PMID:Expression and genetic variability of PCDH11Y, a gene specific to Homo sapiens and candidate for susceptibility to psychiatric disorders. 1633 80

Evidence is presented that RHD, RHCE, and other RH genes, may be interesting candidates to consider when searching for the genetic basis of hair whorl rotation (i.e., clockwise or counterclockwise), handedness (i.e., right handed, left handed or ambidextrous), speech laterality (i.e., right brained or left brained), speech dyslexia (e.g., stuttering), sexual orientation (i.e., heterosexual, homosexual, bisexual, or transsexual), schizophrenia, bipolar disorder, and autism spectrum disorder. Such evidence involves the need for a genetic model that includes maternal immunization to explain some of the empirical results reported in the literature. The complex polymorphisms present among the maternally immunizing RH genes can then be used to explain other empirical results. Easily tested hypotheses are suggested, based upon genotypic (but not phenotypic) frequencies of the RH genes. In particular, homozygous dominant individuals are expected to be less common or lacking entirely among the alternative phenotypes. If it is proven that RH genes are involved in brain architecture, it will have a profound effect upon our understanding of the development and organization of the asymmetrical vertebrate brain and may eventually lead to a better understanding of the developmental processes which occur to produce the various alternative phenotypes discussed here. In addition, if RH genes are shown to be involved in the production of these phenotypes, then the evolutionary studies can be performed to demonstrate the beneficial effect of the recessive alleles of RHD and RHCE, and why human evolution appears to be selecting for the recessive alleles even though an increase in the frequency of such alleles may imply lower average fecundity among some individuals possessing them.
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PMID:The genetic basis of hair whorl, handedness, and other phenotypes. 1633 93

Arginine vasopressin functions as a neurochemical signal in the brain to affect social behavior. There is an expanding literature from animal and human studies showing that vasopressin, through the vasopressin 1A receptor (V1A), can stimulate aggressive behavior. Using a novel monocylic beta lactam platform, a series of orally active vasopressin V1a antagonists was developed with high affinity for the human receptor. SRX251 was chosen from this series of V1a antagonists to screen for effects on serenic activity in a resident-intruder model of offensive aggression. Resident, male Syrian golden hamsters were given oral doses of SRX251 or intraperitoneal Manning compound, a selective V1a receptor antagonist with reduced brain penetrance, at doses of 0.2 microg, 20 microg, 2 mg/kg or vehicle. When tested 90-120 min later, SRX251, but not Manning compound, caused a significant dose-dependent reduction in offensive aggression toward intruders as measured by latency to bite and number of bites. The reduction in aggression persisted for over 6 h and was no longer present 12 h post treatment. SRX251 did not alter the amount of time the resident investigated the intruder, olfactory communication, general motor activity, or sexual motivation. These data corroborate previous studies showing a role for vasopressin neurotransmission in aggression and suggest that V1a receptor antagonists may be used to treat interpersonal violence co-occurring with such illness as ADHD, autism, bipolar disorder, and substance abuse.
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PMID:Orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior. 1650 76

The 67 and 65 kDa isoforms of glutamic acid decarboxylase, the key enzymes for GABA biosynthesis, are expressed at altered levels in postmortem brain of subjects diagnosed with schizophrenia and related disorders, including autism and bipolar illness. The predominant finding is a decrease in GAD67 mRNA levels, affecting multiple brain regions, including prefrontal and temporal cortex. Postmortem studies, in conjunction with animal models, identified several mechanisms that contribute to the dysregulation of GAD67 in cerebral cortex. These include disordered connectivity formation during development, abnormal expression of Reelin and neural cell adhesion molecule (NCAM) glycoproteins, defects in neurotrophin signaling and alterations in dopaminergic and glutamatergic neurotransmission. These mechanisms are likely to operate in conjunction with genetic risk factors for psychosis, including sequence polymorphisms residing in the promoter of GAD1 (2q31), the gene encoding GAD67. We propose an integrative model, with multiple molecular and cellular mechanisms contributing to transcriptional dysregulation of GAD67 and cortical dysfunction in psychosis.
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PMID:Molecular and cellular mechanisms of altered GAD1/GAD67 expression in schizophrenia and related disorders. 1675 10

Reliable and comprehensive maps of molecular pathways are indispensable for guiding complex biomedical experiments. Such maps are typically assembled from myriads of disparate research reports and are replete with inconsistencies due to variations in experimental conditions and/or errors. It is often an intractable task to manually verify internal consistency over a large collection of experimental statements. To automate large-scale reconciliation efforts, we propose a random-arcs-and-nodes model where both nodes (tissue-specific states of biological molecules) and arcs (interactions between them) are represented with random variables. We show how to obtain a non-contradictory model of a molecular network by computing the joint distribution for arc and node variables, and then apply our methodology to a realistic network, generating a set of experimentally testable hypotheses. This network, derived from an automated analysis of over 3,000 full-text research articles, includes genes that have been hypothetically linked to four neurological disorders: Alzheimer's disease, autism, bipolar disorder, and schizophrenia. We estimated that approximately 10% of the published molecular interactions are logically incompatible. Our approach can be directly applied to an array of diverse problems including those encountered in molecular biology, ecology, economics, politics, and sociology.
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PMID:Self-correcting maps of molecular pathways. 1718 92

Despite its initial promise, there has been both progress and some set backs in genetic studies of the major psychiatric disorders of childhood and adulthood. Finding true susceptibility genes may be delayed because the most genetically informative phenotypes are not being used on a regular basis in linkage analysis and association studies. It is highly likely that using alternative phenotypes instead of DSM diagnostic categories will lead more rapid success in the search for these susceptibility genes. The objective of this paper is to describe the different types of informative phenotypes that can be employed in psychiatric genetic studies, to clarify their uses, to identify several methodologic issues the design and conduct of linkage and association studies that use alternative phenotypes and finally to suggest possible solutions to those difficulties. This is a conceptual review with a focus on methodological issues that may arise in psychiatric genetics and examples are taken from the literature on autism, schizophrenia, bipolar disorder, and alcoholism.
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PMID:Informative phenotypes for genetic studies of psychiatric disorders. 1721 86


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