精神分裂症及其疗效与受体基因的相关性

探讨了近年有关精神分裂症的病因和疗效 ,及其受体基因之间的关系 .精神分裂症的遗传倾向提示其部分病因是在基因上 ,多巴胺、5 HT(5羟色胺 )等假说是解释精神分裂症病因机制的主要生化假说 ,这两方面提示精神分裂症与D、5 HT等受体基因可能存在重要联系     

Neuroreplacement therapy and stem cell biology under disease conditions

Recent advances in stem cell technology are expanding our ability to replace a variety of cells throughout the body. In the past, neurological diseases caused by the degeneration of neuronal cells were considered incurable because of a long-held 'truism'; neurons do not regenerate during adulthood. However, this statement has been challenged, and we have now found much evidence that the brain is indeed capable of regenerating neurons after maturing. Based on this new concept, researchers have shown neural differentiation of stem cells and recovery of function following transplantation of these cells into the brain. These results may promise a bright future for clinical applications of stem cell strategies in neurological diseases; however, we must consider the pathophysiological environments of individual diseases that may affect stem cell biology. Before we begin to develop clinical applications, we must consider environmental factors that have not been discussed in the current preclinical studies. Here, we study cases of Alzheimer's disease and schizophrenia and discuss the effects of environmental factors under disease conditions.Received 15 January 2003; received after revision 7 April 2003; accepted 8 April 2003     

The Holistic Sense of Prison Phenomena in Venezuela. I. Understanding and Comprehending “Schizophrenic” Institutions

This is the first in a series of three papers which report on the results of an interpretive systemic study of the prison system and its reform in Venezuela. After explaining the purpose and contents of the trilogy, this paper proceeds to describe the research process undertaken (following the methodological guidelines of interpretive systemology) to open the scene (or uncover the background) of the distinction of prisons as schizophrenic institutions. The study, as a whole, aims at both illustrating the use of interpretive systemology concepts and helping prison reformers to have a better understanding of the complex social situation they aspire to change.     

Aneuploidy in the normal and diseased brain

The brain is remarkable for its complex organization and functions, which have been historically assumed to arise from cells with identical genomes. However, recent studies have shown that the brain is in fact a complex genetic mosaic of aneuploid and euploid cells. The precise function of neural aneuploidy and mosaicism are currently being examined on multiple fronts that include contributions to cellular diversity, cellular signaling and diseases of the central nervous system (CNS). Constitutive aneuploidy in genetic diseases has proven roles in brain dysfunction, as observed in Down syndrome (trisomy 21) and mosaic variegated aneuploidy. The existence of aneuploid cells within normal individuals raises the possibility that these cells might have distinct functions in the normal and diseased brain, the latter contributing to sporadic CNS disorders including cancer. Here we review what is known about neural aneuploidy, and offer speculations on its role in diseases of the brain. Received 13 April 2006; received after revision 2 June 2006; accepted 13 July 2006     

First episode psychosis with extrapyramidal signs prior to antipsychotic drug treatment

Extrapyramidal movement disorders are common in chronic schizophrenia, and may be an intrinsic feature of the illness as well as related to antipsychotic drug treatment. Similar dysfunctions at illness onset may have implications for outcome, and for under- standing the mechanisms of illness. The objectives were to examine the clinical correlates of pre-treatment movement disorders at first episode of psychosis, and determine associations with neuropsychological function and striatal structure. Never medicated subjects were recruited from consecutive admissions to Early Psychosis Programs with defined catchment areas in Hong Kong, China, and Halifax, Canada. Standardized clinical, neuropsychological and brain imaging assessments were carried out at baseline and following acute and long term treatment with typical or atypical antipsychotic drugs. At the Hong Kong site, we studied 84 subjects with first episode psychosis (n = 10 with EPS). At the Halifax site, we studied 40 subjects with first episode psychosis (n = 17 with EPS), and 23 healthy comparison subjects. Subjects with movement disorders prior to treatment (EPS+) had higher total PANSS scores at baseline (mean elevation 19.9% Hong Kong, P = 0.016; 14.7% Halifax, P = 0.049). In subjects treated with atypical antipsychotics (all Halifax), EPS+ status at baseline predicted more movement disorders at long term follow up (P = 0.0005). In both cohorts, EPS+ subjects had poorer acute symptomatic treatment response assessed with the PANSS (Hong Kong P = 0.005; Halifax P = 0.017). Neuropsychological impairment related to executive dysfunction appeared greater in a small sam- ple of EPS+ subjects (Hong Kong, effect size 0.26-0.27, P < 0.05). Caudate volumes were 4.5% larger in EPS+ compared with EPS-subjects (Halifax P = 0.042), and correlations between striatal volumes and age were different in the EPS+ group. In conclu- sion, pre-treatment EPS is present in a substantial minority of subjects with first episode psychosis, appears to persist at long term follow up, and is associated with poorer response of symptoms to treatment. Selective impairment of executive function and stria- tal enlargement provides evidence of abnormalities of brain function and structure associated with this aspect of early psychosis.     

Pathway-based analysis for genome-wide association studies of schizophrenia to provide new insight in schizophrenia study

Schizophrenia (SZ) is an inheritable complex mental disease. There have been several genome-wide association studies (GWASs) of SZ to identify novel genetic susceptibility factors. To further interpret SZ GWASs, pathway-based analysis (PBA), which considers the combined effect of variants and identifies pathways associated with traits, provides a feasible solution to discover the biological function and mechanism of SZ. Furthermore, to investigate the common pathways between SZ and bipolar disorder (BD) wil...     

Is there an anatomical endophenotype for neurodevelopmental disorders？ A review of dual disorder anatomical likelihood estimation （ALE） meta-analyses of grey matter volumes

The term "neurodevelopmental disorder" broadly encompasses conditions thought to arise early in development and includes schizophrenia, bipolar disorder and autism among others. These conditions share a number of genetic and environmental risk factors postulated to lead to common difficulties in socio-emotional processing, communication and cognitive function. The alternative position is that, while the same traits are affected across these conditions, the nature or direction in which they are modified may be distinct. MRI studies provide a rapidly expanding and rich database which we propose can be used to contribute to this debate. Anatomical likelihood estimation (ALE) is a method of meta-analysis applied to voxel-based MRI studies. We have adapted this method to explore the extent to which schizophrenia and bipolar disorder and schizophrenia and autism share a common brain structural phenotype. We will review this work here and discuss whether there is sufficient other evidence to justify a common framework for further research into the inter-relatedness of such conditions.     

On the physiology of metazoa

The problem of integration and control of the various processes of the metazoan organism is a major challenge to the physiologist. The traditional research strategy in dealing with the problem is neuron-oriented and its roots extend back into the last century when knowledge of hormones was lacking. In the present article, the traditional strategy is analyzed in the light of available data and its logical basis is questioned. Different levels of communication are supposed to occur in the animal or human body. Circulating hormones are responsible for the highest level of communication that occurs between organs or tissues. The central concept in the article is that regulation of circulating hormones constitutes a higher level of control relative to regulation of intercellular hormones. This is regardless of whether the latter occurs in the nervous system or elsewhere. The approach is utilized in defining the mechanism that integrates and controls the part processes of the body. The mechanism is defined as endothelial; the vascular endothelial system is the controlling part and the nervous system is one of the subordinate parts. Thanks to the new approach, meaningful biological explanations of major psychiatric disorders are now possible.     

The right neuron at the wrong place: biology of heterotopic neurons in cortical neuronal migration disorders, with special reference to associated pathologies

During the development of the neocortex, neurogenesis and neuronal differentiation occur in two separate locations. Thus neurons have to migrate through the future white matter. Arrested or excessive migration leads neurons to differentiate in a heterotopic position. Such neuronal migration disorders (NMDs) occur sporadically in normal development but are markedly increased as a consequence of genetic defects or after exposure to toxic drugs during the period of migration. Anatomofunctional studies in rodents with NMDs have revealed that heterotopic neurons form essentially normal afferent and efferentconnections, which has been interpreted as evidence that the connectionpattern of cortical neurons is specified prior to migration. In addition, recent data show that heterotopic neurons can be contacted by environmental, that is local, fibres that normally never innervate the neocortex. This dual connectivity leads heterotopias to form bridges between their environmental and original network. Such an abnormal pattern of connectivity could contribute to the pathophysiology of disorders associated with NMDs such as epilepsy. Received 16 December 1998; received after revision 5 February 1999; accepted 9 February 1999     

Physiological functions of D-amino acid oxidases: from yeast to humans

D-Amino acid oxidase (DAAO) is a FAD-containing flavoenzyme that catalyzes the oxidative deamination of D-isomers of neutral and polar amino acids. This enzymatic activity has been identified in most eukaryotic organisms, the only exception being plants. In the various organisms in which it does occur, DAAO fulfills distinct physiological functions: from a catabolic role in yeast cells, which allows them to grow on D-amino acids as carbon and energy sources, to a regulatory role in the human brain, where it controls the levels of the neuromodulator D-serine. Since 1935, DAAO has been the object of an astonishing number of investigations and has become a model for the dehydrogenase-oxidase class of flavoproteins. Structural and functional studies have suggested that specific physiological functions are implemented through the use of different structural elements that control access to the active site and substrate/product exchange. Current research is attempting to delineate the regulation of DAAO functions in the contest of complex biochemical and physiological networks.