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

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

Klinefelter syndrome (KS) is a chromosomal condition (47, XXY) that may help us to unravel gene-brain behavior pathways to psychopathology. The phenotype includes social cognitive impairments and increased risk for autism traits. We used functional MRI to study neural mechanisms underlying social information processing. Eighteen nonclinical controls and thirteen men with XXY were scanned during judgments of faces with regard to trustworthiness and age. While judging faces as untrustworthy in comparison to trustworthy, men with XXY displayed less activation than controls in (i) the amygdala, which plays a key role in screening information for socio-emotional significance, (ii) the insula, which plays a role in subjective emotional experience, as well as (iii) the fusiform gyrus and (iv) the superior temporal sulcus, which are both involved in the perceptual processing of faces and which were also less involved during age judgments in men with XXY. This is the first study showing that KS can be associated with reduced involvement of the neural network subserving social cognition. Studying KS may increase our understanding of the genetic and hormonal basis of neural dysfunctions contributing to abnormalities in social cognition and behavior, which are considered core abnormalities in psychiatric disorders such as autism and schizophrenia.
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PMID:Neural systems for social cognition in Klinefelter syndrome (47,XXY): evidence from fMRI. 2173 34

Klinefelter's syndrome is a sex chromosome abnormality with low androgen level. The varied manifestations of the mental symptoms in some of them, that are inexplicable based on their genotype alone, has fascinated the researchers. We present here a case of Klinefelter's syndrome having a karyotype of mos 47, XXY, and also inversion in 9(th) chromosome, with schizophrenia. Despite the view that inv 9 is a normal variant, it is still worthwhile to explore whether it has any role in the etiology of schizophrenia especially when it occurs with other genotypic aberrations that are suspected to have relevance to psychiatric disorders including the Klinefelter's syndrome.
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PMID:Klinefelter's syndrome (mosaic) with chromosome 9 inv and schizophrenia. 2255 46

Klinefelter's syndrome (KS; karyotype 47,XXY) is associated with specific neurocognitive impairments, especially delayed language development and impaired socioemotional evolution. There is an increased risk for psychiatric disturbances, particularly schizophrenia and affective spectrum disorders. A 51-year-old monozygotic male twin with KS is described of whom one was referred for long-lasting paranoid psychotic symptoms. Both were treated with testosterone and had an average level of intelligence. Detailed psychiatric and neuropsychological assessment in the referred patient demonstrated quasi-psychotic symptoms with illusions, delusion-like ideas, paranoid ideation, magical thinking, circumstantial speech and thinking and eccentric behaviours. In addition, attentional deficits and executive dysfunctions could be demonstrated. A diagnosis of schizotypal personality disorder was made. A less pronounced identical clinical picture was found in his brother. The psychopathological phenotype of KS is characterised by a schizotypal personality which originates from its specific cognitive defects and that, with increasing age, may develop into a schizophrenia-like psychosis.
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PMID:Schizotypy: key feature of Klinefelter's syndrome? 2268 40

According to the social defeat (SD) hypothesis, published in 2005, long-term exposure to the experience of SD may lead to sensitization of the mesolimbic dopamine (DA) system and thereby increase the risk for schizophrenia. The hypothesis posits that SD (ie, the negative experience of being excluded from the majority group) is the common denominator of 5 major schizophrenia risk factors: urban upbringing, migration, childhood trauma, low intelligence, and drug abuse. The purpose of this update of the literature since 2005 is to answer 2 questions: (1) What is the evidence that SD explains the association between schizophrenia and these risk factors? (2) What is the evidence that SD leads to sensitization of the mesolimbic DA system? The evidence for SD as the mechanism underlying the increased risk was found to be strongest for migration and childhood trauma, while the evidence for urban upbringing, low intelligence, and drug abuse is suggestive, but insufficient. Some other findings that may support the hypothesis are the association between risk for schizophrenia and African American ethnicity, unemployment, single status, hearing impairment, autism, illiteracy, short stature, Klinefelter syndrome, and, possibly, sexual minority status. While the evidence that SD in humans leads to sensitization of the mesolimbic DA system is not sufficient, due to lack of studies, the evidence for this in animals is strong. The authors argue that the SD hypothesis provides a parsimonious and plausible explanation for a number of epidemiological findings that cannot be explained solely by genetic confounding.
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PMID:The social defeat hypothesis of schizophrenia: an update. 2406 92

Klinefelter syndrome (KS) is the most common sex-chromosome aneuploidy in humans. Most affected individuals carry one extra X-chromosome (47,XXY karyotype) and the condition presents with a heterogeneous mix of reproductive, physical and psychiatric phenotypes. Although the mechanism(s) by which the supernumerary X-chromosome determines these features of KS are poorly understood, skewed X-chromosome inactivation (XCI), gene-dosage dysregulation, and the parental origin of the extra X-chromosome have all been implicated, suggesting an important role for epigenetic processes. We assessed genomic, methylomic and transcriptomic variation in matched prefrontal cortex and cerebellum samples identifying an individual with a 47,XXY karyotype who was comorbid for schizophrenia and had a notably reduced cerebellum mass compared with other individuals in the study (n = 49). We examined methylomic and transcriptomic differences in this individual relative to female and male samples with 46,XX or 46,XY karyotypes, respectively, and identified numerous locus-specific differences in DNA methylation and gene expression, with many differences being autosomal and tissue-specific. Furthermore, global DNA methylation, assessed via the interrogation of LINE-1 and Alu repetitive elements, was significantly altered in the 47,XXY patient in a tissue-specific manner with extreme hypomethylation detected in the prefrontal cortex and extreme hypermethylation in the cerebellum. This study provides the first detailed molecular characterization of the prefrontal cortex and cerebellum from an individual with a 47,XXY karyotype, identifying widespread tissue-specific epigenomic and transcriptomic alterations in the brain.
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PMID:Epigenomic and transcriptomic signatures of a Klinefelter syndrome (47,XXY) karyotype in the brain. 2447 18

Klinefelter syndrome is a disorder of variation of sex chromosome, the most common karyotype being 47XXY. Multiple case reports and articles have been published linking the increased prevalence of psychiatric disorders like Schizophrenia, Schizophreniform psychosis, Attention deficit hyperkinetic disorder, Learning disorder, etc. and seizure disorder in Klinefelter syndrome than in general population, attributing to the extra X chromosome. Here is a case of a 45-year-old gentleman with Klinefelter syndrome with schizophrenia-like psychosis and seizure disorder. He was diagnosed as Klinefelter syndrome 15 years back by genetic testing (47XXY) when he was investigated for infertility. His luteinizing hormone (LH) (32.04 mIU/ml) and follicle-stimulating hormone (FSH) (50.70 mIU/ml) levels were high and his testosterone level was low (1.76 ng/ml). He had four episodes of seizures in 2004 for which he was started on phenytoin and sodium valproate, and was seizure-free for past 10 years. He was brought to our hospital in July 2014 with complaints of talking and laughing to self, suspicion, hearing voices and aggressive behaviour, which were persistent mildly for past 15 years and aggravated for past 6 months. He was not going for work for past 15 years, does not mingle with relatives or friends.
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PMID:A Case Report of Klinefelter Syndrome with Schizophrenia-Like Psychosis and Seizure Disorder. 2666 93

The coincidence or causal incidence of hormonal dysregulation leading to psychotic manifestation had been a point of debate. The interplay of these hormones in pathogenesis of psychotic symptom domains is still inconclusive along with some symptom domains which worsen with antipsychotics. Early detection and treatment with liaison approach is of great help to such patients. We report a case of schizophrenia with primary hypogonadism that responded dramatically to add on testosterone supplement.
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PMID:Add on testosterone therapy in negative symptoms of schizophrenia with gonadal trauma: Hitting the bull's eye. 2713 16

The X chromosome has long been an intriguing site for harboring genes that have importance in brain development and function. It has received the most attention for having specific genes underlying the X-linked inherited intellectual disabilities, but has also been associated with schizophrenia in a number of early studies. An X chromosome hypothesis for a genetic predisposition for schizophrenia initially came from the X chromosome anomaly population data showing an excess of schizophrenia in Klinefelter's (XXY) males and triple X (XXX) females. Crow and colleagues later expanded the X chromosome hypothesis to include the possibility of a locus on the Y chromosome and, specifically, genes on X that escaped inactivation and are X-Y homologous loci. Some new information about possible risk loci on these chromosomes has come from the current large genetic consortia genome-wide association studies, suggesting that perhaps this hypothesis needs to be revisited for some schizophrenias. The following commentary reviews the early and more recent literature supporting or refuting this dormant hypothesis and emphasizes the possible candidate genes still of interest that could be explored in further studies.
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PMID:The Sex Chromosome Hypothesis of Schizophrenia: Alive, Dead, or Forgotten? A Commentary and Review. 3039 96

Klinefelter syndrome (KS) 47, XXY is the most frequent chromosomal abnormality causing hypogonadism in humans. This chromosomal abnormality of number in its classical form called homogeneous (supernumerary X) is generally the result of a meiosis accident. Several studies have suggested that individuals with KS are at greater risk of developing various psychiatric disorders, including depression and schizophrenia. The diagnosis is made based on subnormal testosterone with high pituitary gonadotropins and confirmed by determining the karyotype on a blood simple. We did a literature review using an electronic search in three databases: Pubmed/MEDLINE, Google Scholar, and PsychInfo. We found that since 1989, seven case reports with KS and mental disorders with similar and different characteristics of our case illustration of a patient with KS and psychosis were published.
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PMID:Sexual Identity Disorder and Psychosis in Klinefelter Syndrome: A Synthesis of Literature and a Case Report. 3067 80


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