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M ental I llnessC oncernsA ll | Two matters can be picked out from this exciting Report new( available on www.loni.ucla.edu/~thompson/HBM 2001 ) It is the parietal lobe which is where the process starts. 1.Changes there are noticeable in the parietal lobe two years before a pattern develops which is like that found in adults where schizophrenia is diagnosed. 2. The commentary remarks that where a monzygotic twin does not have schizophrenia these changes have not occurred. The explanation offered is that the changes are a reaction to environmental influence - which can be different, even in monozygotic twins. "... We recently found that the parietal regions, specifically, are also in deficit in adult patients relative to genetically identical controls (their monozygotic discordant twins). This indicates that environmental, and not purely genetic, factors are implicated in triggering this deficit, at least in adults.... " The conclusion made is that - because genesis is the same - the differences in phenotype must be nurtural difference.The comment in the discussion is that this suggests the phenotype in the well twin has some environmental difference which protects ? This is not a valid conclusion. There are ways - which even in monozygotic twins from the same cell and genes, turn out differently . One - unlikely - is that retrovirus exposure may enter and alter dna/rna expression after the twins have gone some way along in their developments. ( see below (*) That it is the parietal area which is first to show change is relevant for what is thought to be a deficit in schizophrenia. A basic explantation is that what Sch. sees or hears is what everybody sees and hears but the Sch. puts a different linkage on it, and upon that, a delusional 'tail' is accepted whcih remains to sustain and direct other interpretations. The parietal lobe takes sensation so far - here shared with peer processing agrees with what is seen by others, but it is the individual frontal lobe which places what has been received into significance and perhaps directs the rest of the brain - memories -schema habits created by the cerebellum - ongoing associative sgnificances in current memory - into a governing perspectives. Another Report from ucla adds a flavour of where we may be going to explain schizophrenia 'There is currently a great interest in understanding attentional processing at the cellular, neurosystems, and behavioral levels. Data from cognitive, electrophysiological, metabolic, developmental, and brain-lesion studies converge to suggest that in normal processing, selective attention operations require coordinated interaction among frontal, parietal, brainstem, and thalamic systems. Although much is understood about systems involved in sustaining a single focus of attention, much less is known about the neural operations involved in the rapid changing of attentional maps during shifts in the focus of attention. Until recently, models of the neural systems involved in attention did not include a role for the cerebellum. However, based on anatomical connections and recent physiological data, Courchesne and colleagues ( from the same campus as Thompson - do they talk ) proposed that neocerebellar lesions may lead to dysfunction in attentional processes. In our laboratory, we are testing this new model by studying patients with focal cerebellar lesions and patients with autism, a disorder involving Purkinje neuron loss restricted to the neocerebellum. Neuroanatomical characteristics of patients are obtained by volumetric analyses of abnormal and spared anatomical regions. Neurophysiological activity is recorded while patients and controls perform tasks testing attentional capacity. Results show that neocerebellar damage impairs the ability to rapidly and accurately change attentional maps during shifts of attention between auditory and visual information as well as between perceptual domains (locations, color, form) within the visual modality. These findings have led to new concepts about the role of the human neocerebellum in mental as well as motor operations, and to a new theory of the neural basis for infantile autism, a developmental disorder characterized by severe impairment in joint social attention. Ongoing structural and functional neuroimaging, neurophysiological, and behavioral studies compare and contrast the roles of the neocerebellum and other neural systems in the dynamic control of selective attention. For instance, we are currently employing functional magnetic resonance imaging (fMRI) to confirm a role for the normal human cerebellum in attention operations, and to test new concepts of cerebellar function that go beyond a traditional motor view. The other major area of research in this lab is the neurodevelop- mental disorder of autism. More than 200 autistic patients and non- autistic controls have entered our ongoing research program. Detailed neurological and neuropsychological testing is performed on these patients and structural magnetic resonance (MR) images are gathered as part of our longitudinal study. Using this information, we have demonstrated hypoplasia of the cerebellum in the majority of autistic patients and a loss of parietal lobe tissue in a subset of autistic patients. These findings correlate with deficits in certain attentional abilities believed to rely on parietal lobe function and have supported a possible role of the cerebellum in attentional function as described above. Ongoing research examines the neuroanatomy of other brain regions which have been implicated in autism (frontal lobes, basal ganglia, etc.) using structural MR imaging. We are also using neurophysiological techniques (ERP) and fMRI techniques to assess cognitive function in autism. We are also beginning an investigation into the genetics of the disorder. ' topOne explanation of lack of concordance in monozygotic twins is that the zygosity testing is insufficent and other testing grounds may show dizygosity i.e mono twins are really dizygotes. One classic analysis of the genetic contribution to disease is the study of schizophrenia and manic-depressive disorder by Torrey et al [6]. Zygosity was assessed using a combination of photos, questionnaires, and nineteen red-blood cell antigens. Years later, aliquots of the original blood samples were examined in the laboratories of Cassandra Smith at Boston University. In this reanalysis, based on hundreds of targeted data points, allegedly MZ pairs discordant for schizophrenia had levels of DNA similarity comparable to the range found in unselected sibling pairs. All others had very high or intermediate similarity levels. One interpretation of these data is that the twin pairs discordant for schizophrenia were actually DZ, despite the fact that competing gene product zygosity assessments were MZ. An alternative interpretation is equally if not more likely, this is, that within the genetic component of schizophrenia, MZ twins exhibit a range of post-zygotic genomic discordance that has not yet completely been 'characterized'. This later explanation is particularly attractive because it addresses the hitherto unanswerable question of why MZ twins are not completely alike. The four presently accepted post-zygotic mechanisms by which MZ twins have been shown to be genetically discordant are as follows: 1) chromosomal differences; 2) X-inactivation difference in females; 3) differential gene imprinting; and 4) post-zygotic mutations. At present no gold standard exists for zygosity assignment using DNA products. Simply stated, there is no agreement as to which biologic sample is preferable (hair, skin, saliva, blood) or whether it is preferable to use tests of low stringency (classic bar code) or tests of high stringency (individual markers). Moreover, if tests of high stringency are used, their number and exact location has yet to be decided upon. In the final analysis, the answer to the question to the number of genetic markers may hinge upon the concept of statistical strength and interpretation, Just as was the case using the older, standard method of testing, e.g. blood groups, one must test enough loci to achieve statistical validity which, in turn would depend on the relative frequency of the allele(s) in the general population. Most post-zygotic mutations do not occur in coding DNA and thus the detection of discordant mutation in non-coding DNA does not immediately render a diagnosis of DZ. It is important to acknowledge that the exact number of mutational differences that lie within the range an acceptable assignment of monozygosity is presently unknown. The issues discussed above are of sufficient importance as to demand a reexamination of the attitudes of contemporary obstetricians to using the placenta for zygosity assignment. Since the advent of ultrasound and the use of vaginal probes early in pregnancy, this modality has been adopted worldwide and is advocated in recent texts and monographs as a means of providing better prenatal care and potentially avoiding some of the complications of monochorionic placentation, such as twin-to-twin transfusion syndrome. The singular advantage of using placentation is that it is a gold-standard in which, for all practical purposes, monochorionic placentation is equivalent to monozygosity. In summary, the simultaneous recognition of the existence of post-zygotic mutations and the awareness that such mutations may result in a number of differences within MZ pairs the need for suggested a new paradigm [7]. We now propose a four-tier classification system, respecting the classical definition of zygosity and addressing contemporary medical scientific issues most likely to cause confusion: Level I – assessment by fetal membrane status (monochorionic = MZ) — dichorionic like sex does not mandate DZ state Level II – phenotypic characteristics – MZ, discordant for schizophrenia, diabetes, cancer, etc. Level III – genotypic characteristics – possible discordant for coding (single gene disease) or non-coding DNA region, for example Level IV – genomic characteristics – 93% similar using Targeted Genomic Differential Display (TGDD), 99% similar using bar code, for example. In the final analysis, obstetricians have an obligation to play active and informed roles in the process of assigning zygosity by ensuring that early and accurate assessments of membranes and placenta(s) are obtained by high quality ultrasound early in pregnancy [5]. After birth, pathologic confirmation of antenatally diagnosed chorion states should be placed in the chart with a copy given to the parents, remembering always that MC=MZ . We advise that all DC like sex pairs have DNA analysis to discern the remaining MZ pairs.
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back to 'a wild theory'
The wild theory is my own. All the other matter is what I have picked off the internet - looking for a way forward. Something else I downloaded but cannot now find the source is this significant sounding sentence ... " Hormonal enhancer at puberty silences residual maternal polyploidy in the cerebellum disrupting memory facilitation by the thalamus and endorhinal cortex " ... it should fit in somewhere! Schizophrenia commonly starts after puberty. My brother spent a little of his time as a neuropathologist confirming cerebellar polyploidy without giving it any particular function - couldn't think of any -1957 or thereabouts
M ental I llness C oncerns A ll