Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Rey Dot Counting Test was administered to 100 patients with suspect effort drawn from two separate settings (personal injury/disability, n=86; prison hospital, n=14) and to 251 subjects in nine clinical groups (head injury, learning disability, right and left cerebrovascular accident, schizophrenia, older normals, depressed elderly, and mild and moderate dementia). Sensitivity of cut-offs for individual test scores (mean grouped dot counting time, ratio of mean grouped to ungrouped dot counting time, and number of errors) differed markedly across the two suspect effort groups (e.g., 28-100%), indicating that noncredible patients drawn from different settings employ somewhat differing approaches in their fabrication of cognitive symptoms. Use of a cut-off of > or =17 applied to a combination score (mean ungrouped dot counting time+meangrouped dot counting time+number of errors) resulted in 100% sensitivity in the forensic suspect effort group and 75% sensitivity in the civil litigation/disability suspect effort group, while maintaining specificity of > or =90% for the clinical groups combined (excluding moderate dementia).
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PMID:Sensitivity and specificity of the Rey Dot Counting Test in patients with suspect effort and various clinical samples. 1459 47

We employed voxel-based morphometry (VBM) to compare the distributions of grey matter found in structural magnetic resonance imaging (MRI) brain scans of patients with comorbid learning disability with schizophrenia, schizophrenia alone, learning disability alone, and normal controls. Our primary aim was to replicate a previous region of interest (ROI) finding that comorbids and schizophrenics belong to the same population. Nonparametric analysis in normalized space showed no significant differences in grey matter distribution between the comorbid and schizophrenia groups. Furthermore, this analysis showed significant grey matter reductions in the comorbid and schizophrenia groups when compared to the learning-disabled or the normal controls. Parametric analysis localized the significant grey matter reductions between the normal controls and the comorbid and schizophrenia groups to the prefrontal and temporal lobes. It also identified an area of increased grey matter, on the inferior aspect of the postcentral gyrus, in the learning-disabled alone compared to the other groups. Native space parametric and nonparametric analyses, based on modulation of the normalized scans, confirmed the similarity in grey matter distribution of the comorbid and schizophrenia groups. Results confirm the ROI finding that in native space the learning-disabled group possesses the least and normal controls the most grey matter for the cohort. An increase in the basal ganglia of patients with schizophrenia vs. the learning-disabled, probably attributable to antipsychotic medication, was identified in the native space analysis. The native space results did not however register statistically significant temporal lobe reductions found under normalized analysis between schizophrenics and normal controls. This may be attributable to minor physical anomalies (MPA) in the schizophrenic cranium. Overall, these VBM results replicate previous ROI findings and are compatible with the view that comorbid learning disability with schizophrenia is a severe form of schizophrenia, rather than a consequence of learning disability. VBM has the facility to compare grey matter distributions in this structurally diverse cohort.
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PMID:Voxel-based morphometry of comorbid schizophrenia and learning disability: analyses in normalized and native spaces using parametric and nonparametric statistical methods. 1511 9

Cognitive plasticity, a developmental trait that promotes acquisition of complex skills such as language or playing musical instruments, diminishes substantially during puberty. The loss of plasticity has been attributed to surge of sex steroids during adolescence, but the phenomenon remains poorly understood. We hypothesize that pineal involution during puberty may contribute to plasticity decay. The pineal gland produces melatonin, the level of which declines dramatically during onset of puberty. Emerging evidence suggest that melatonin may modulate cognitive plasticity, independent of the effects of sex steroids, and low sex steroids and high melatonin may be simultaneously required to maintain cognitive plasticity. Potential mechanisms by which melatonin may modulate plasticity are examined within the sleep and hippocampal long-term potentiation frameworks. Implications for psychiatric conditions that involve sleep disorders and learning dysfunctions such as schizophrenia and autism are discussed, and the potential adaptive roles of postprandial and postcoital sleep are explored. From the Darwinian perspective, development and reproductive maturity may represent distinct phases that require tailored cognitive strategies to maximize fitness. While cognitive flexibility and susceptibility to new skills may be paramount during development, reduced cognitive flexibility and increased cognitive determinism may enable more efficient responses to stimuli during adulthood. Thus, cognitive plasticity and cognitive determinism may represent trade-off adaptations and different dimensions of intelligence. The decline of plasticity and emergence of puberty during the second decade may be relics of prehistoric times when the human lifespan was short and the environment was relatively simple and static. Today, when the environment is more complex and dynamic, and humans are living far longer, the early obsolescence of plasticity during puberty may represent a Darwinian inefficiency exposed by evolutionary displacement. Regulation of plasticity may be a systemic phenomenon, as exemplified by the association of learning disability with allergic conditions, a form of immune plasticity dysfunction. Ramifications for other plastic functions that decline during puberty such as wound healing and hyaline cartilage regeneration are explored. Like the plasticity of immunity and cognition, the plasticity of hyaline cartilage during youth may enable hosts to respond to ecologic opportunities and generate the optimally adapted adult phenotype. Pineal involution may represent a potential target for therapeutic extension or restoration of plasticity after puberty. Extending plasticity may have far-reaching consequences for human evolution.
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PMID:Pineal attrition, loss of cognitive plasticity, and onset of puberty during the teen years: is it a modern maladaptation exposed by evolutionary displacement? 1550 60

A mother and daughter diagnosed with schizophrenia and schizophrenia co-morbid with mild learning disability, respectively, possess a balanced reciprocal translocation t(9,14)(q34.2;q13). Fluorescence in situ hybridization (FISH) with YAC, BAC, and cosmid probes indicate that the chromosome 14q13 breakpoint disrupts a large gene, NPAS3, encoding a CNS expressed transcription factor of the basic helix-loop-helix PAS (bHLH-PAS) gene family. By analogy with other members of the bHLH-PAS family, the putative truncated protein generated from the disrupted gene locus may have a dominant negative effect. The 14q13 region was previously identified by a linkage study of an inherited neurodegenerative condition, idiopathic basal ganglia calcification (IBGC or Fahr syndrome, OMIM:213600/606656), which is often co-morbid with psychosis. Sequencing of the gene in a third patient diagnosed with IBGC, schizophrenia, and mild learning disability did not reveal functional mutations.
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PMID:Disruption of a brain transcription factor, NPAS3, is associated with schizophrenia and learning disability. 1592 6

We present an empirical comparison of cluster extent and maximal voxel results in a voxel-based morphometry (VBM) study of brain structure. The cluster extents are adjusted for underlying deviation from uniform smoothness. We implement this comparison on a four-group cohort that has previously shown evidence of a neuro-developmental component in schizophrenia (Moorhead, T.W.J., Job, D.E., Whalley, H.C., Sanderson, T.L., Johnstone, E.C. and Lawrie, S.M. 2004. Voxel-based morphometry of comorbid schizophrenia and learning disability: analyses in normalized and native spaces using parametric and nonparametric statistical methods. NeuroImage 22: 188-202.). We find that adjusted cluster extent results provide information on the nature of deficits that occur in the schizophrenia affected groups, and these important structural differences are not all shown in maximal voxel results. The maximal voxel and cluster extent results are corrected for multiple comparisons using Random Fields (RF) methods. In order to apply the cluster extent measures, we propose a post-hoc method for determining the primary threshold in the analysis. Unadjusted cluster extent results are reported, for these, no allowance is made for non-isotropic smoothness, and comparison with the adjusted extent results shows that the unadjusted results can be either conservative or anti-conservative depending upon the underlying tissue distributions.
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PMID:Empirical comparison of maximal voxel and non-isotropic adjusted cluster extent results in a voxel-based morphometry study of comorbid learning disability with schizophrenia. 1608 27

In the search for the biological causes of schizophrenia and bipolar disorder, glutamate neurotransmission has emerged as one of a number of candidate processes and pathways where underlying gene deficits may be present. The analysis of chromosomal rearrangements in individuals diagnosed with neuropsychiatric disorders is an established route to candidate gene identification in both Mendelian and complex disorders. Here we describe a set of genes disrupted by, or proximal to, chromosomal breakpoints (2p12, 2q31.3, 2q21.2, 11q23.3 and 11q24.2) in a patient where chronic schizophrenia coexists with mild learning disability (US: mental retardation). Of these disrupted genes, the most promising candidate is a member of the kainate-type ionotropic glutamate receptor family, GRIK4 (KA1). A subsequent systematic case-control association study on GRIK4 assessed its contribution to psychiatric illness in the karyotypically normal population. This identified two discrete regions of disease risk within the GRIK4 locus: three single single nucleotide polymorphism (SNP) markers with a corresponding underlying haplotype associated with susceptibility to schizophrenia (P=0.0005, odds ratio (OR) of 1.453, 95% CI 1.182-1.787) and two single SNP markers and a haplotype associated with a protective effect against bipolar disorder (P=0.0002, OR of 0.624, 95% CI 0.485-0.802). After permutation analysis to correct for multiple testing, schizophrenia and bipolar disorder haplotypes remained significant (P=0.0430, s.e. 0.0064 and P=0.0190, s.e. 0.0043, respectively). We propose that these convergent cytogenetic and genetic findings provide molecular evidence for common aetiologies for different psychiatric conditions and further support the 'glutamate hypothesis' of psychotic illness.
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PMID:Cytogenetic and genetic evidence supports a role for the kainate-type glutamate receptor gene, GRIK4, in schizophrenia and bipolar disorder. 1681 33

A three-fold enhanced risk of schizophrenia is conferred by learning disability. Here we use voxel-based morphometry (VBM) to investigate grey matter correlates of early psychotic and related symptoms in 137 adolescents at enhanced risk of this disorder because of intellectual disability. Anxiety, hallucinations, incoherence of speech and delusions were assessed at clinical interview, and VBM was used to examine linear associations between symptom severity and grey matter density (GMD). We found significant correlations between anxiety and GMD in the right dorsomedial thalamic nucleus, left parahippocampal gyrus and left hippocampus. Incoherence of speech was associated with GMD in the left cerebellar hemisphere. Gender-separate analysis demonstrated correlations between anxiety and GMD in the right dorsomedial thalamic nucleus of males and the right pulvinar nucleus of females, hallucinations and GMD in the right STG of males, delusions and GMD in the left middle temporal gyrus (MTG) of females, and incoherence of speech and GMD in the right MTG of males and both cerebellar hemispheres and right inferior temporal gyrus of females. Findings are consistent with symptom-structure associates previously reported in populations with schizophrenia or at enhanced genetic risk, and suggest an anatomical basis for the psychopathology found in this young nonclinical population.
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PMID:Grey matter correlates of early psychotic symptoms in adolescents at enhanced risk of psychosis: a voxel-based study. 1732 Apr 16

The literature regarding offending in the learning disabled population is limited; the effects of normalisation and deinstitutionalisation on offending behaviour is not yet determined. We retrospectively examined 93 court reports completed by the Tayside learning disability service since 1986. Twenty patients were not considered to be learning disabled. Sixty-four of the subjects deemed learning disabled faced charges, the most common being public order offences, which was in common with previous reports. Eighteen per cent of these had a co-morbid mental illness, the majority attracting a diagnosis of schizophrenia. Inpatient assessment, assessment as a day patient or probation were recommended for about two-thirds. Fewer than 50% of cases had no psychiatric recommendation made to the court. There was a predominance of arson and sexual offending. Arsonists were twice as likely as sex offenders to be recommended for inpatient treatment.
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PMID:Offending in the learning disabled population: a retrospective audit of Tayside learning disability service court reports. 1834 Nov 55

Underactivity of the glutamatergic system is an attractive model for the pathophysiology of several major mental illnesses. We previously described a chromosome abnormality disrupting the kainate class ionotropic glutamate receptor gene, GRIK4/KA1, in an individual with schizophrenia and learning disability (mental retardation). We also demonstrated in a case-control study that two physically separated haplotypes within this gene were significantly associated with increased risk of schizophrenia and decreased risk of bipolar disorder, respectively. The latter protective haplotype was located at the 3' end of the gene. We now report the identification from carriers of the protective haplotype of a deletion variant within the 3' untranslated region of the gene. The deletion allele also was found to be negatively associated with bipolar disorder in both initial (P = 0.00000019) and replication (P = 0.0107) case-control studies. Expression studies indicated that deletion-carrying mRNA transcripts were relatively more abundant. We postulate that this may be a direct consequence of the differences in the RNA secondary structures predicted for the insertion and deletion alleles. These data suggest a mechanism whereby the genetic protective effect is mediated through increased kainate receptor expression.
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PMID:A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. 1882 90

Rare copy number variants (CNVs) are frequently associated with common neurological disorders such as mental retardation (MR; learning disability), autism, and schizophrenia. CNV screening in clinical practice is limited because pathological CNVs cannot be distinguished routinely from benign CNVs, and because genes underlying patients' phenotypes remain largely unknown. Here, we present a novel, statistically robust approach that forges links between 148 MR-associated CNVs and phenotypes from approximately 5,000 mouse gene knockout experiments. These CNVs were found to be significantly enriched in two classes of genes, those whose mouse orthologues, when disrupted, result in either abnormal axon or dopaminergic neuron morphologies. Additional enrichments highlighted correspondences between relevant mouse phenotypes and secondary presentations such as brain abnormality, cleft palate, and seizures. The strength of these phenotype enrichments (>100% increases) greatly exceeded molecular annotations (<30% increases) and allowed the identification of 78 genes that may contribute to MR and associated phenotypes. This study is the first to demonstrate how the power of mouse knockout data can be systematically exploited to better understand genetically heterogeneous neurological disorders.
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PMID:Forging links between human mental retardation-associated CNVs and mouse gene knockout models. 1955 86


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