Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fatty acids of cell membrane phospholipids are essential for normal membrane structures, for the functioning of membrane-bound and membrane-associated proteins and for normal cell-signalling responses. In dyslexia, there is evidence for reduced incorporation of docosahexaenoic acid and arachidonic acid into cell membranes, while in schizophrenia, there is evidence for an increased rate of docosahexaenoic acid and arachidonic acid loss from membranes because of enhanced phospholipase A2 activity. The presence of both defects will cause a much greater degree of abnormality than either one alone. It is hypothesized that unequivocal clinical schizophrenia may occur when both genes are present in the same individual. The dyslexia gene along will produce dyslexia while the schizophrenia gene alone may produce bipolar or schizoaffective disorders. These proposals could explain: 1. The reduced asymmetry of the brain, especially of the planum temporale in both schizophrenia and dyslexia; 2. The schizotypal personality characteristics of dyslexics; 3. The increased risks of dyslexia in families with a schizophrenic proband; 4. The increased risks of bipolar and schizoaffective disorders in families with a schizophrenic proband; 5. The earlier onset and possibly increased severity of both disorders in males since females have a lower requirement for arachidonic acid and docosahexaenoic acid; 6. The absence of selective pressure against schizophrenia since reproduction would be impaired only when the schizophrenic gene coexisted with a dyslexic gene. The schizophrenic gene alone might even lead to improved reproductive performance.
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PMID:Possible relevance of phospholipid abnormalities and genetic interactions in psychiatric disorders: the relationship between dyslexia and schizophrenia. 877 Oct 57

Any hypotheses concerning the origins of humans must explain many things. Among these are: 1, the growth in brain size around two million years ago; 2, the presence of subcutaneous fat; 3, the near absence of change or cultural progress for around 2 million years after the brain grew in size; 4, the cultural explosion which began somewhere between fifty thousand and one hundred thousand years ago with the emergence of art, music, religion and warfare; 5, the further cultural explosion around ten thousand to fifteen thousand years ago which developed with the emergence of agriculture and which has continued since. Since the brain, like subcutaneous fat, is particularly rich in lipids, and since the microconnections of the brain are substantially lipid in nature, it is suggested that changes in lipid metabolism are what differentiated humans from the great apes. The growth in brain size and in the quality of subcutaneous adipose tissue may have occurred because of changes in the proteins which regulate the rate of delivery of fatty acids to tissues, notably lipoprotein lipases and fatty acid binding proteins. The creativity which occurred one hundred thousand years ago may have resulted from changes in phospholipid-synthesizing, -remodelling and -degrading enzymes which largely determine the microconnectivity of neurons. Family studies and adoption studies indicate that schizophrenia in a family member is associated with an increased risk of the illness in other family members. It is also associated with an increased risk of schizotypy, manic-depression, dyslexia, sociopathy and psychopathy. On the other hand it is also an indication of an increased likelihood of high creativity, leadership qualities, achievements in many fields, high musical skills and an intense interest in religion. I propose that the characteristics which entered the human race about one hundred thousand years ago and which ended around two million years of cultural near-stagnation are precisely those shown by the families of people with schizophrenia. I propose that these features are caused by variations in phospholipid biochemistry which are responsible both for schizophrenia and for our humanity. This would help to explain why schizophrenia is present to approximately the same degree in all races. It is the illness which made us human prior to the separation of the races.
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PMID:Schizophrenia: the illness that made us human. 969 Jul 63

The planum temporale (PT) is a triangular area situated on the superior temporal gyrus (STG), which has enjoyed a resurgence of interest across several disciplines, including neurology, psychiatry and psychology. Traditionally, the planum is thought to be larger on the left side of the brain in the majority of normal subjects [N. Geschwind, W. Levitsky, Human brain: left-right asymmetries in temporal speech regions, Science 161 (1968) 186-87.]. It coincides with part of Wernicke's area and it is believed to consist cytoarchitectonically of secondary auditory cortex. Consequently, it has long been thought to be intimately involved in language function. The PT is, therefore, of relevance to disorders where language function is impaired, such as schizophrenia and dyslexia. The gross anatomical boundaries remain in dispute, and only recently has its cytoarchitecture begun to be studied again after 60 years silence, and finally its functional significance is only now being explored. In the first part of this review the structural aspects and anatomical boundaries of the PT in the normal brain from post mortem and magnetic resonance imaging (MRI) and methods of measurement are discussed. In the second part, studies of the functional significance of the PT in the normal brain are reviewed critically. Finally a meta-analysis of MRI measurements of the distribution of planum anatomy in normal subjects is presented. Comparison is made with clinical populations, including schizophrenia and dyslexia, and the influence of handedness and gender on such measurements is quantified. Although there are many ways of defining and measuring the PT with a wide variety of results, overall there is a significant leftward asymmetry in normals, which is reduced in left handers and females. The leftward asymmetry is much reduced in patients with schizophrenia due to a relatively larger right PT than normal controls. The review is intended to guide future researchers in this area.
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PMID:The planum temporale: a systematic, quantitative review of its structural, functional and clinical significance. 997 50

Anomalies in the laterality of numerous neurocognitive dimensions associated with schizophrenia have been documented, but their role in the etiology and early development of the disorder remain unclear. In the study of normative neurobehavioral organization, animal models have shed much light on the mechanisms underlying and the factors affecting adult patterns of both functional and structural asymmetry. Nonhuman species have more recently been used to investigate the environmental, genetic, and neuroendocrine factors associated with developmental language disorders in humans. We propose that the animal models used to study the basis of lateralization in normative development and language disorders such as dyslexia could be modified to investigate lateralized phenomena in schizophrenia.
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PMID:Laterality in animals: relevance to schizophrenia. 1009 13

Family and adoption studies indicate that genetic factors play a role in the development of many psychiatric disorders. A variable number of possible interacting genes giving a predisposition to the diseases is likely. The genetic dissection has been hampered by genetic complexity as well as by difficulties in defining the phenotypes. Genetic mapping efforts using sib pairs, twins and individual large families have revealed preliminary or tentative evidence of susceptibility loci for a number of psychiatric disorders. Illnesses described in this article include the prion disease familial fatal insomnia (FFI), alcoholism, anorexia nervosa, autism, bipolar affective disorder, dyslexia, enuresis nocturna, epilepsia, obsessive-compulsive disorders (OCD), schizophrenia, and the dementias, Alzheimer's disease and frontal lobe dementia. The genes and proteins related to the newly discovered transmitter in the central nervous system, nitric oxide (NO), and its genes and proteins are also reviewed. The number of mapped human genes now exceeds 30,000 of the estimated total number of 60,000 to 100,000 genes. This rapid development will facilitate gene mapping and efforts to isolate and identify the genes responsible for symptom susceptibility in many of the aetiologically unclear psychiatric diseases with complex genetic origin.
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PMID:[Complex hereditary diseases with psychiatric symptoms]. 1010 48

The right shift (RS) theory (Annett, M., 1972. The distribution of manual asymmetry. Br. J. Psychol. 63, 343-358; Annett, M., 1985. Left, Right, Hand and Brain: The Right Shift Theory. Lawrence Erlbaum, London) suggests that the typical pattern of human cerebral and manual asymmetries depends on a single gene (RS+) which impairs speech-related cortex of the right hemisphere. The theory offers solutions to several puzzles, including the distribution of handedness in families (Annett, M., 1978. A Single Gene Explanation of Right and Left Handedness and Brainedness. Lanchester Polytechnic, Coventry; Annett, M., 1996. In defense of the right shift theory. Percept. Motor Skills 82, 115-137), relations between handedness and cerebral speech laterality (Annett, M., 1975. Hand preference and the laterality of cerebral speech. Cortex 11, 305-328; Annett, M., Alexander, M.P., 1996. Atypical cerebral dominance: predictions and tests of the right shift theory. Neuropsychologia 34, 1215-1227) and handedness and dyslexia (Annett, M. et al., 1996. Types of dyslexia and the shift to dextrality. J. Child Psychol. Psychiatry 37, 167-180). If Crow's (Crow, T.J. et al., 1989. Schizophrenia as an anomaly of development of cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of the disease. Arch. Gen. Psychiatry 46, 1145-1150; Crow, T.J., 1997. Is schizophrenia the price that Homo sapiens pays for language? Schizophr. Res. 28, 127-141) theory that schizophrenia is due to an anomaly of cerebral dominance is correct, and if the RS theory is correct, schizophrenia could be due to an anomaly of the RS+ gene. If the RS+ gene were at risk for a mutation which caused a loss of directional coding, the mutant could be described as 'agnosic' for left and right. Such a gene would impair either hemisphere at random. When paired with another RS+ gene, both hemispheres would be impaired in 50% of cases. The other 50% and people in whom the agnosic gene is paired with an RS-allele (neutral for asymmetry and not giving hemisphere impairment) would have one unaffected hemisphere and, thus, normal development. Quantitative predictions based on the RS genetic theory as previously developed, plus an agnosic mutant with frequency required to give schizophrenia in 1% of the population, are consistent with estimates of concordance for schizophrenia in relatives. Homozygotes of the agnosic mutant would occur at about the rate estimated for autism.
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PMID:The theory of an agnosic right shift gene in schizophrenia and autism. 1050 10

The planum temporale (PT) bias, PT leftward, PT symmetry, and PT rightward reversal and sidedness preference, consistent right-handedness, ambilaterality, and consistent left-handedness are placed on a continuum mirroring the normal variation in rate of brain maturation. Maturational rate declines as we pass from PT leftward bias and consistent right-handedness to PT reversal and consistent left-handedness. Concomitantly, we expect an increased prevalence of males due to their pubertal age being about 2 years later than that of females, and a shift in cognitive profile from higher verbal scores than performance scores on the WAIS to higher performance than verbal scores. Three disorders fulfilling the criteria of late CNS maturation apart from the corresponding cognitive profile were studied: infantile autism (IA), schizophrenia (S), and developmental dyslexia (DD). These disorders have in common deficits in cognition, perception, and somatomotor function. The deficits range from an arrest in brain development (which is evident in infancy superimposed on late maturation in IA) to overall delayed brain and somatic development in S (culminating in postpubertal psychotic episodes and persistent and generalized residual deficits). Finally, reading inability, problems in perception (vision and hearing) and in motor coordination, particularly between the two hemispheres, characterize DD. Enhancing brain maturation and the prevalence of 'normal' cerebral asymmetry--laterality is preferable if we want to reduce the risk of developing the above-mentioned disorders. It is suggested that in the past environmental challenges have favored early maturation, with its abundant neuronal population, arborization and excessive density of synapses and cerebral excitability which has powered evolution through the mechanism of natural selection. Early maturation is obtainable through optimal nutrition, including a satisfactory amount of marine fat (PUFA), before and during pregnancy and later in life.
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PMID:A lack of cerebral lateralization in schizophrenia is within the normal variation in brain maturation but indicates late, slow maturation. 1050 11

Sexual dimorphisms and/or hormone modifiability have been documented for numerous structural endpoints in the cerebral cortex, including cortical thickness and dendrite morphology. The present study asked whether gonadal steroids might also sculpt cortical circuit organization. Accordingly, neonatal gonadectomy, with and without testosterone propionate replacement, was followed by fine-grained microcircuit tract tracing analyses of the organization of corticocortical circuits of identified layers of primary motor and primary visual cortices in the same animals in adulthood. Comparative analyses revealed neither qualitative nor quantitative differences in visual cortical circuit organization between gonadectomized and control animals. In primary motor cortex, circuit organization was also qualitatively similar in the two animal groups. However, quantitative analyses uncovered small, but highly consistent, decreases in the horizontal breadth of motor cortical connections in the hormonally deprived group. These decreases were attenuated in gonadectomized rats that were supplemented with testosterone propionate. Furthermore, quantitative analysis of cytoarchitecture revealed that visual and motor circuits in both gonadectomized groups resided in cortical areas with dimensions that were statistically invariant from corresponding measures obtained in control animals. These findings suggest that cortical circuits should be among anatomical substrates considered in relation to observed sex differences in and/or hormone modifiability of the maturation of identified cortical functions. These findings may also have relevance for cortical dysmaturation and dysfunction in disorders such as schizophrenia and dyslexia, diseases in which sex differences in incidence suggest some role for gonadal steroids.
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PMID:Perinatal gonadectomy affects corticocortical connections in motor but not visual cortex in adult male rats. 1054 63

Family and adoption studies indicate that genetic factors play a role in the development of many psychiatric disorders. A variable number of possible interacting genes predisposing to the diseases is likely. The genetic dissection has been hampered by genetic complexity as well as by difficulties in defining the phenotypes. Genetic mapping efforts using sib pairs, twins and individual large families has revealed preliminary or tentative evidence for susceptibility loci for a number of psychiatric disorders. Illnesses include the prion disease familial fatal insomnia (FFI), alcoholism, anorexia nervosa, autism, bipolar affective disorder, dyslexia, enuresis nocturnal, epilepsia, obsessive-compulsive disorders (OCD), schizophrenia, as well as the dementias, Alzheimer's disease and frontal lobe dementia, and mental retardation. The genes and proteins related to the newly discovered transmitter in the central nervous system, nitric oxide (NO), and its genes and proteins are also reviewed. The number of mapped human genes now exceeds 30,000 of the estimated total number of 60,000 to 100,000 genes. This rapid development will facilitate gene mapping, as well as efforts to isolate and identify the genes responsible for symptom susceptibility in many of the etiologically unclear psychiatric diseases with complex genetic origin.
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PMID:[Mental disease a heritage. New genetic knowledge can reveal "public diseases" such as autism, dyslexia, alcoholism, anorexia, schizophrenia]. 1070 80

Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans.
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PMID:Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. 1085 51


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