Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current evidence suggests that the effects of lithium on metabolic and signaling pathways in the brain may vary depending on the specific clinical condition or disease model. For example, lithium increases levels of cerebral N-acetyl aspartate in patients with bipolar disorder but does not appear to affect N-acetyl aspartate levels in normal human subjects. Conversely, lithium significantly decreases whole-brain levels of N-acetyl aspartate in a rat genetic model of Canavan disease in which cerebral N-acetyl aspartate is chronically elevated. While N-acetyl aspartate is a commonly used surrogate marker for neuronal density and correlates with neuronal viability, grossly elevated whole-brain levels of N-acetyl aspartate in Canavan disease are associated with dysmyelination and mental retardation. This report describes the first clinical application of lithium in a human subject with Canavan disease. Spectroscopic and clinical changes were observed over the time period in which lithium was administered, which reversed during a 2-week wash-out period after withdrawal of lithium. This investigation reports decreased N-acetyl aspartate levels in the brain regions tested and magnetic resonance spectroscopic values that are more characteristic of normal development and myelination, suggesting that a larger, controlled trial of lithium may be warranted as supportive therapy for Canavan disease by decreasing abnormally elevated N-acetyl aspartate.
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PMID:Lithium citrate for Canavan disease. 1619 20

This study explores shoplifting behaviour in mentally ill patients, and evaluates the association between shoplifting and different mental illnesses in a local Chinese population. A comparison is made between shoplifting offenders and a matched control group of non-offenders among the psychiatric patients registered at a university department of psychiatry. Major depression, bipolar affective disorder (BAD) and mental retardation (MR) are the most common diagnoses among mentally ill shoplifters, while patients with a diagnosis of BAD or MR are at higher risk of committing an offence than patients with other diagnoses. Bipolar affective disorder has not been described as a risk factor for shoplifting behaviour in the psychiatric literature. Such a possibility should be seriously considered in the psychiatric assessment of shoplifting cases.
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PMID:Shoplifting in the mentally ill: the role of bipolar affective disorder and mental retardation. 1630 77

We report on a young woman with Jacobsen syndrome (JBS) who was admitted to our psychiatric department because of a bipolar affective disorder (BPAD). Chromosome analysis was performed due to the fact that she had mental retardation, short stature, and subtle facial anomalies. A deletion of the distal long arm of chromosome 11 was found. A detailed mapping of the deletion breakpoint by quantitative real time PCR revealed a true terminal 11q deletion of approximately 8 Mb corresponding to the karyotype 46,XX,del(11)(q24.2). Polymorphic DNA marker analysis showed that the deletion is located on the paternal chromosome. Additionally, laboratory investigations revealed a low platelet count and magnetic resonance imaging of the brain showed white matter T2 hyperintensities in frontotemporal regions, which are unlikely to result from a demyelinating process as indicated by localized proton magnetic resonance spectroscopy. To our knowledge, this is the first report describing a BPAD in a case with JBS.
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PMID:Association of Jacobsen syndrome and bipolar affective disorder in a patient with a de novo 11q terminal deletion. 1641 36

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

In ADHD, impaired interpersonal relationships have been documented. They have been hypothesized to be secondary to impairment of receptive nonverbal language. Recognition of emotional facial expressions is an important aspect of receptive nonverbal language, and it has been demonstrated to be central to organization of emotional and social behavior. This study investigated the identification of facial expression of four emotions (joy, anger, disgust, and sadness) in a group of 30 children aged 7-12 years who met the DSM-IV criteria for ADHD disorder of the predominantly hyperactive-impulsive type and have no comorbid mental retardation, specific learning difficulties, developmental coordination disorder, pervasive developmental disorders, conduct disorder, bipolar disorder, or substance abuse, and in 30 matched unimpaired control children. The test used includes 16 validated photographs depicting these emotions in varying intensities constructed by morphing. Children with ADHD exhibited a general deficit in decoding emotional facial expressions, with specific deficit in identifying anger and sadness. Self-rating of the task difficulty revealed lack of awareness of decoding errors in the ADHD group as compared with control subjects. Within the ADHD group, there was a significant correlation between interpersonal problems and emotional facial expression decoding impairment, which was more marked for anger expressions. These results suggest suboptimal nonverbal decoding abilities in ADHD that may have important implications for therapy.
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PMID:Recognition of emotional facial expressions in attention-deficit hyperactivity disorder. 1687 3

Self-mutilation is form of self-injurious behavior which is either low intensity, high frequency form seen in personality disorder and mental retardation or low frequency, highly destructive form which occurs in the context of psychosis or acute intoxications. We report a 32 yr-old male with bipolar affective disorder presenting with multiple acts of major self-mutilation during an episode of psychotic depression. At presentation he had broken upper central incisors, circular burn scar on right palm, crush injury of left index finger with avulsed nail and cut injury over glans penis. In view of his extreme self-mutilating behavior, he was administered electroconvulsive therapy on second day following which self-mutilating behavior improved after fourth ECT. After 8 ECT sessions, he was started on lithium carbonate with a serum level of 0.82 meq/L and haloperidol 15 mg/day and there was no recurrence of self-mutilating behavior during follow up after four months.
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PMID:[Electroconvulsive therapy for multiple major self-mutilations in bipolar psychotic depression]. 1856 Oct 53

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

Genetic factors contribute to schizophrenia and bipolar disorder, and linkage and association studies have been successful in identifying several candidate genes. However these genes explain only a very small part of the total population risk and the psychoses appear to be very heterogeneous with several models of genetic inheritance relevant to different groups of patients, including some cases caused by multiple common genetic variants, while others are single gene disorders. Studying chromosomal abnormalities is a useful strategy for identifying genes in illness, and patients with both mental retardation and psychosis form a special group where large chromosomal abnormalities detected by routine cytogenetic analysis are more prevalent than in patients with schizophrenia or bipolar disorder alone, or in the general population. Studying these patients provides valuable opportunities to identify genes contributing to psychoses. This review of the literature on large chromosomal rearrangements in patients with mental retardation and psychotic illness illustrates how schizophrenia and bipolar phenotypes are associated with a large number of different chromosomal disruptions. Recent genome wide association studies have identified an excess of small chromosomal deletions and duplications in schizophrenia, adding further support to the importance of chromosomal structural variation in psychotic illness. The genes GRIK4 and NPAS3, each associated with psychosis in patients with mental retardation are discussed to illustrate the value of rare cytogenetic events as a means to signpost neurobiological pathways of general importance for illness in the wider population.
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PMID:Chromosome abnormalities, mental retardation and the search for genes in bipolar disorder and schizophrenia. 1907 19

A 55-year-old man with congenital hemiparesis of the right side, three episodes of generalised tonic-clonic seizure at 16 years of age, and two episodes of severe depression and two episodes of hypomania in the past, presented with severe depression with psychotic symptoms. Computed tomography of the brain showed a grey matter-lined cerebrospinal fluid-filled cleft in the left cerebral hemisphere, involving the temporoparietal region. He was diagnosed to have bipolar II disorder, and was currently severely depressed with psychotic symptoms and schizencephaly. He improved with sodium valproate 1,000 mg/day, quetiapine 450 mg/day and escitalopram 20 mg/day after three weeks without any emergent side effects, and was maintaining well at three months follow-up. Although uncommon, schizencephaly may be considered as one of the differentials in cases of bipolar disorder along with congenital hemiparesis, mental retardation and/or seizures; and neuroimaging should be done to confirm the diagnosis.
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PMID:Schizencephaly associated with bipolar II disorder. 1929 19

The major psychotic illnesses, schizophrenia and bipolar disorder (BD), are among the most heritable common disorders, but finding specific susceptibility genes for them has not been straightforward. The reasons are widely assumed to include lack of valid phenotypic definition, absence of good theories of pathophysiology for candidate gene studies, and the involvement of many genes, each making small contributions to population risk. Within the last year or so, a number of genome wide association (GWAS) of schizophrenia and BD have been published. These have produced stronger evidence for association to specific risk loci than have earlier studies, specifically for the zinc finger binding protein 804A (ZNF804A) locus in schizophrenia and for the calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C) and ankyrin 3, node of Ranvier (ANK3) loci in bipolar disorder. The ZNF804A and CACNA1C loci appear to influence risk for both disorders, a finding that supports the hypothesis that schizophrenia and BD are not aetiologically distinct. In the case of schizophrenia, a number of rare copy number variants have also been detected that have fairly large effect sizes on disease risk, and that additionally influence risk of autism, mental retardation, and other neurodevelopmental disorders. The existing findings point to some likely pathophysiological mechanisms but also challenge current concepts of disease classification. They also provide grounds for optimism that larger studies will reveal more about the origins of these disorders, although currently, very little of the genetic risk of either disorder is explained.
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PMID:Genetics of psychosis; insights from views across the genome. 1952 22


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