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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1991 the American Psychiatric Association proposed a draft version of the IV edition of the Diagnostic and Statistical Manual of Mental Disorders--the DSM IV Options Book. Authors of this version wanted to increase clarity of the criteria sets and to provide compatibility with the Tenth Edition of the International Classification of Diseases (ICD - 10). The purpose of this Options Book is to propose some changes in wording, diagnostic divisions and to discuss various options concerning the placement of sections and disorders within the classification. The "Disorders of Infancy, Childhood or Adolescence" section was renamed "Disorders Usually First Evident in Infancy, Childhood or Adolescence" and moved to the front of the classification and also was expended to 11 groups of disorders. Several suggestions have been made about including new diagnostic groupings such as: Rett's Disorder, Eating Disorders and Voice Disorder. The Options Book introduces a superior category for Attention Deficit Disorders (with and without hyperactivity) and for Conduct Disorder/Oppositional Defiant Disorder. Several options are proposed regarding The Anxiety Disorders of Childhood or Adolescence. There is no evidence for a distinction in this category according to the age criterion. One option would be to move these disorders into the adult anxiety section (similarly as in the Mood Disorders and Schizophrenia). In the new version the title "Specific Developmental Disorders" is omitted. The suggestion is to include Phonological Disorder (Articulation Disorders) and Elective Mutism into Speech and Language Disorders section.
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PMID:[Developmental disorders in the fourth edition of the American classification: diagnostic and statistical manual of mental disorders (DSM IV -- optional book)]. 752 63

In 1991 the American Psychiatric Association proposed a draft version of the IV edition of Diagnostic and Statistical Manual of Mental Disorders--the DSM IV Options Book. Authors of this version wanted to increase clarity of the criteria sets and to provide compatibility with the Tenth Edition of the International Classification of Diseases (ICD-10). The purpose of this Options Book is to propose some changes in wording, diagnostic divisions and to discuss various options concerning the placement of sections and disorders within the classification. The "Disorders of Infancy, Childhood or Adolescence" section was renamed "Disorders Usually First Evident in Infancy, Childhood or Adolescence" and moved to the front of the classification and also was expended to 11 groups of disorders. Several suggestions have been made about including new diagnostic groupings such as: Rett's Disorder, Eating Disorders and Voice Disorder. The Options Book introduces a superior category for Attention Deficit Disorders (with and without hyperactivity) and for Conduct Disorder/Oppositional Defiant Disorder. Several options are proposed regarding The Anxiety Disorders of Childhood or Adolescence. Since there is no evidence for distinction in this category according to the age criterion, one option would be to move these disorders into the adult anxiety section (similarly to the Mood Disorders and Schizophrenia). In the new version the title "Specific Developmental Disorders" is omitted. The suggestion is to include Phonological Disorder (Articulation Disorders) and Elective Mutism in the Speech and Language Disorders section.
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PMID:[Anxiety disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association: diagnostic and statistical manual of mental disorders (DMS-IV -- options book]. 820 69

A model for a new approach to neuropsychiatric gene linkage is proposed in the context of increased chromosomal breakage which has recently been reported in association with Tourette syndrome, schizophrenia, Rett syndrome and the psychopathology associated with mentally normal, female obligate fra-X carriers. Chromosomal fragility may be connected with the formation of unstable repeat sequences at multiple sites resulting in a continuum of effects, ranging from advantageous evolutionary changes, to more serious neurobehavioural disorders, with neurodegenerative states on the extreme end of the spectrum. The current major problem with phenotype-genotype correlations in complex neuropsychiatric disorders may, therefore, be due to the distance between a postulated breakage-enhancing effect of the primary gene(s), and the continuum of diverse phenotypes resulting from the secondary-gene involvement at a varying number of fragile sites. A unifying view of behavioural alteration, viewed in anthropogenetic context, rather than a DSM-based reductionist approach may be required for the elucidation of psyche-destabilizing genetic changes.
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PMID:A paradigmatic shift in the approach to neuropsychiatric gene linkage may require an anthropogenetic perspective. 877 Oct 44

Fluorescence in situ hybridization (FISH) of DNA-DNA or DNA-RNA using post-mortem brain samples is one approach to study low-level chromosomal aneuploidy and selective expression of specific genes in the brain of patients with neuropsychiatric diseases. We have performed a pilot molecular-cytogenetic analysis of post-mortem brain of schizophrenic patients. Multicolor FISH on two post-mortem brain samples of normal individuals and six schizophrenic individuals (area 10 of cortex) was applied. A set of DNA probes for FISH included: (i) centromeric alphoid DNA probes for chromosomes 7, 8, 13 and 21, 18, X and Y; (ii) classical satellite DNA probes for chromosomes 1 and 16; and (iii) region-specific DNA probes for chromosomes 13, 21 and 22. A statistically significant level of aneuploidy (up to 0.5-4% of neurons) involving chromosomes X and 18 was detected in two post-mortem brains of patients with schizophrenia. These results indicate that low-level chromosomal aneuploidy could be involved in the pathogenesis of schizophrenia. FISH could be applied to extended studies of chromosomal aneuploidy, abnormal patterns of chromosomal organization and functional gene expression in situ in the neurons of the brain in different psychiatric and neurodevelopmental diseases. Schizophrenia and Rett syndrome might be considered as psychiatric diseases of special interest for molecular-cytogenetic analysis as both of them could be associated with mutations in genes involving regulation of neurodevelopmental processes in the brain.
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PMID:Multicolor fluorescent in situ hybridization on post-mortem brain in schizophrenia as an approach for identification of low-level chromosomal aneuploidy in neuropsychiatric diseases. 1173 70

Mutations in the gene coding for methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome (RTT) and have also been reported in a number of X-linked mental retardation syndromes. Furthermore, putative mutations recently have been described in a few autistic patients and a boy with language disorder and schizophrenia. In this study, DNA samples from individuals with schizophrenia and other psychiatric diseases were scanned in order to explore whether the phenotypic spectrum of mutations in the MECP2 gene can extend beyond the traditional diagnoses of RTT in females and severe neonatal encephalopathy in males. The coding regions, adjacent splicing junctions, and highly conserved segments of the 3'-untranslated region (3'-UTR) were examined in 214 patients, including 106 with schizophrenia, 24 with autism, and 84 patients with other psychiatric diseases by detection of virtually all mutations-single strand conformation polymorphism (SSCP) (DOVAM-S). To our knowledge, this is the first analysis of variants in conserved regions of the 3'-UTR of this gene. A total of 5.2 kb per haploid gene was analyzed (1.5 Mb for 214 patients). A higher frequency of missense and 3'-UTR variants was found in autism. One missense and two 3'-UTR variants were found in 24 patients with autism versus one patient with a missense change in 144 ethnically similar individuals without autism (P = 0.009). These mutations suggest that a possible association between MECP2 mutations and autism may warrant further study.
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PMID:MECP2 structural and 3'-UTR variants in schizophrenia, autism and other psychiatric diseases: a possible association with autism. 1521 31

Brain imaging represents a potent tool to characterize biomarkers, biological traits that are pathognomonic for specific neurological and neuropsychiatric disorders. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are imaging techniques used to identify alterations in the density and distribution of neurotransmitters, neuroreceptors, and transporters in specific regions of the brains of people with these disorders. Brain imaging research currently facilitates the elucidation of dysfunction of dopamine, serotonin, acetylcholine, and other substances in people with Alzheimer's and Parkinson's diseases, schizophrenia, alcoholism and other substance abuse disorders, attention deficit/hyperactivity disorder, and the syndromes of restless legs, Lesch-Nyhan, Rett, and Tourette. Thus, brain imaging research offers great potential for the diagnosis, treatment, prevention, and cure of neurological and neuropsychiatric disorders. Brain imaging research also facilitates new drug development and helps establish therapeutic doses of novel drugs. In particular, studies of specific receptors, such as the dopamine D2 receptor, before and after the administration of doses of drugs that occupy these D2 receptors, provide the means to determine receptor occupancy. For example, an optimal dose of D2 antagonist antipsychotics produces occupancy of 65% to 80% of D2 receptors, while a greater dose carries a risk of extrapyramidal side effects.
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PMID:Brain imaging research: does the science serve clinical practice? 1789 34

I review and evaluate genetic and genomic evidence salient to the hypothesis that the development and evolution of psychotic spectrum conditions have been mediated in part by alterations of imprinted genes expressed in the brain. Evidence from the genetics and genomics of schizophrenia, bipolar disorder, major depression, Prader-Willi syndrome, Klinefelter syndrome, and other neurogenetic conditions support the hypothesis that the etiologies of psychotic spectrum conditions commonly involve genetic and epigenetic imbalances in the effects of imprinted genes, with a bias towards increased relative effects from imprinted genes with maternal expression or other genes favouring maternal interests. By contrast, autistic spectrum conditions, including Kanner autism, Asperger syndrome, Rett syndrome, Turner syndrome, Angelman syndrome, and Beckwith-Wiedemann syndrome, commonly engender increased relative effects from paternally expressed imprinted genes, or reduced effects from genes favouring maternal interests. Imprinted-gene effects on the etiologies of autistic and psychotic spectrum conditions parallel the diametric effects of imprinted genes in placental and foetal development, in that psychotic spectrum conditions tend to be associated with undergrowth and relatively-slow brain development, whereas some autistic spectrum conditions involve brain and body overgrowth, especially in foetal development and early childhood. An important role for imprinted genes in the etiologies of psychotic and autistic spectrum conditions is consistent with neurodevelopmental models of these disorders, and with predictions from the conflict theory of genomic imprinting.
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PMID:Genomic imprinting in the development and evolution of psychotic spectrum conditions. 1878 62

Cell adhesion molecules at neuronal synapses regulate diverse aspects of synaptic development, including axo-dendritic contact establishment, early synapse formation, and synaptic maturation. Recent studies have identified several synaptogenic adhesion molecules. The NGL (netrin-G ligand; LRRC4) family of synaptic cell adhesion molecules belongs to the superfamily of leucine-rich repeat (LRR) proteins. The three known members of the NGL family, NGL-1, NGL-2, and NGL-3, are mainly localized to the postsynaptic side of excitatory synapses, and interact with the presynaptic ligands, netrin-G1, netrin-G2, and LAR, respectively. NGLs interact with the abundant postsynaptic density (PSD) protein, PSD-95, and other postsynaptic proteins, including NMDA receptors. These interactions are thought to couple synaptic adhesion events to the assembly of synaptic proteins. In addition, NGL proteins regulate axonal outgrowth and lamina-specific dendritic segmentation, suggesting that the NGL-dependent adhesion system is important for the development of axons, dendrites, and synapses. Consistent with these functions, defects in NGLs and their ligands are associated with impaired learning and memory, hyperactivity, and an abnormal acoustic startle response in transgenic mice, and schizophrenia, bipolar disorder, and Rett syndrome in human patients.
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PMID:The NGL family of leucine-rich repeat-containing synaptic adhesion molecules. 1946 32

The approval of suberoylanilide hydroxamic acid by the FDA for the treatment of cutaneous T-cell lymphoma in October, 2006 sparked a dramatic increase in the development of inhibitors for the class of enzymes known as the histone deacetylases (HDACs). In recent years, a large number of combination therapies involving histone deacetylase inhibitors (HDACIs) have been developed for the treatment of a variety of malignancies and neurodegenerative disorders. Promising evidence has been reported for the treatment of pancreatic cancer, prostate cancer, and leukemia as well as a number of other previously difficult to treat cancers. Drug combination approaches have also shown promise for the treatment of mood disorders including bipolar disorder and depression. In addition to these drug combination approaches, HDACIs alone have demonstrated effectiveness in the treatment of Parkinson's disease, Alzheimer's disease, Rubinstein-Taybi syndrome, Rett syndrome, Friedreich's ataxia, Huntington's disease, multiple sclerosis, anxiety, and schizophrenia. Adverse inflammatory affects observed with traumatic brain injury and arthritis have also been alleviated by treatment with certain HDACIs. Based on the diverse utility and wide range of mechanistic actions observed with this class of drugs, the future development of better drug combination therapies and more selective HDACIs is warranted.
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PMID:Creating zinc monkey wrenches in the treatment of epigenetic disorders. 1954 31

DNA methylation is an epigenetic mechanism in which the methyl group is covalently coupled to the C5 position of the cytosine residue of CpG dinucleotides. DNA methylation generally leads to gene silencing and is catalyzed by a group of enzymes known as DNA methyltransferases (Dnmt). During development, the epigenome undergoes waves of demethylation and methylation changes. As a result, there are cell type/tissue-specific DNA methylation patterns. Since DNA methylation changes only happen during DNA replication to maintain methylation patterns on hemimethylated DNA or establish new methylation, Dnmt expression generally decreases greatly after cell division. However, significant levels of Dnmts were noticed specifically in postmitotic neurons, suggesting a functional importance of Dnmt in the nervous system. Accumulating evidence showed that DNA methylation correlates with certain neuropsychiatric disorders such as schizophrenia, Rett syndrome, and ICF syndrome. Studies of methyl-CpG-binding proteins, Dnmt inhibitors, and Dnmt knockout mice also explored the key role of DNA methylation in neural development, plasticity, learning, and memory. Though an enzyme exhibiting DNA demethylation capability in vertebrates still remains to be identified, DNA methylation status in the CNS appeared to be reversible at certain genomic loci. This supports a maintenance role of Dnmt to prevent active demethylation in postmitotic neurons. Taken together, DNA methylation provides an epigenetic mechanism of gene regulation in neural development, function, and disorders.
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PMID:The role of DNA methylation in the central nervous system and neuropsychiatric disorders. 1990 Jun 16


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