The Gilles de la Tourette syndrome is a usually chronic neuropsychiatric disorder with an early childhood onset featuring mainly motor and vocal tics. It seems that strong genetic factors make a major contribution to the etiology of this disorder, but there are also clues that epigenetic factors are involved in the pathogenesis of Tourette's syndrome, such as maternal stress during pregnancy, birth complications and hormonal influences.
Cerebellar granule cells isolated from postnatal day 7 rat pups are ideal for studying epigenetic events associated with the regulation of neuronal gene expression. These cultures contain from 90 to 95% glutamatergic granule cells and express mRNAs encoding a variety of ionotropic and metabotropic glutamate receptors as well as virtually all of the GABAA-receptor subunit mRNAs to different extents. A unique feature of this culture system is that the neurons undergo time-dependent maturation changes in vitro that mimic many of the characteristics of these receptors occurring in vivo.
PURPOSE: To describe the phenotypic variability in a Polish Norrie disease (ND) family associated with the missense mutation A63D. METHODS: A patient with spared vision from a Polish ND family underwent detailed ophthalmological examinations including slit-lamp biomicroscopy, ultrasound (USG), angiography, Goldmann kinetic visual field, and electroretinography (ERG). Mutation screening was carried out using the single-strand conformation polymorphism (SSCP) technique and subsequent DNA sequencing of the coding part of the ND gene.
Twin Research: The Official Journal of the International Society for Twin Studies
Non-linear epigenetic processes are a potential underlying source of phenotypic differences in development. Simulation studies of twin pairs using simple non-linear development models characterised by chaotic or near-chaotic behavior are presented. The effect of chaotic processes on correlations is to lower them from their initial values, but high initial correlations are affected much less by chaotic and near-chaotic processes than intermediate correlations.
Annett, Yeo et al. and Klar have each proposed theories that relate the genetics of cerebral lateralization to predisposition to psychosis. These theories are considered in relation to the central paradox that psychosis is associated with a substantial biological disadvantage. Annett's heterozygote advantage hypothesis critically identified lateralization as a major determinant of ability, but it appears that what is inherited is degrees (as suggested by Yeo et al.) rather than (or as well as) direction of lateralization.
This paper is a review of studies examining the neurobehavioral antecedents of schizophrenia which flesh out neurodevelopmental models of schizophrenia by detailing the time course of the ontogeney of neurobehavioral impairments in schizophrenia. A follow back design was used to identify precursors of psychotic symptoms in children with a schizophrenic disorder. The vast majority of children with a schizophrenic disorder had significant developmental delays beginning early in life.
Developments in molecular biology over the past three decades have led to an increasing awareness of the importance of epigenetic phenomena in a variety of genome functions. Epigenetic aspects of complex multifactorial diseases including schizophrenia, however, have not been investigated sufficiently. Various facets of epigenetics are reevaluated through their putative relevance to four theories of schizophrenia: neurodevelopmental, dopamine dysfunction, viral, and genetic anticipation with unstable DNA.
Evidence is reviewed that one of the cognitive-affective parallel circuits in the brain, the dorsolateral prefrontal circuit, is compromised at the level of anatomical, neuropathological and transmitter-related molecules in a subgroup of schizophrenic patients. The dorsolateral prefrontal cortex (DLPFC) comprises a key structure in this circuit.
Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
A number of recent clinical and molecular observations in major psychosis indicate that epigenetic factors may be operational in the origin of major mental illness. This article further develops the idea that epigenetic factors may play an etiopathogenic role in schizophrenia and bipolar affective disorder. The putative role of epigenetic factors is shown by the epigenetic interpretation of genetic association studies of the genes for serotonin 2A (HTR2A) and the dopamine D3 (DRD3) receptors in schizophrenia.
The hypothesis that a gene for susceptibility to psychosis (specifically in the X-Y homologous class) is located on the sex chromosomes has been proposed. Such a gene would account for the excess of sex chromosome anomalous males and females in populations of patients with psychosis, a tendency towards concordance by sex within families, and sex differences associated with psychosis and its underlying brain pathology. In earlier studies we observed small positive LOD scores in Xp11, and in a more recent and larger cohort of 178 sibling pairs, a peak multipoint nonparametric LOD score of 1.