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T J Crow

Publications and source records attributed to T J Crow.

At least 163 records · Page 9Linked to original sources
PubMed1990

An in-frame insertion in the prion protein gene in familial Creutzfeldt-Jakob disease.

In a pedigree with Creutzfeldt-Jakob disease we identified a 144-bp insertion in the open reading frame of the prion protein (PrP) gene. The insertion is in-frame and codes for 6 extra uninterrupted octapeptide repeats in addition to the 5 that are normally present in the N-terminal region of the protein. The possibility that this mutation may prove relevant to elucidating the mechanism of horizontal transmission of the spongiform encephalopathies is discussed.

Amino Acid Sequence↗
PubMed1990

Schizophrenia and the brain: a prospective clinico-neuropathological study.

The neuropathological results from a prospective, systematically assessed, series of 56 schizophrenic patients and 56 age- and sex-matched normal controls have been presented. When compared with the normal controls, the brains of the schizophrenic subjects showed a significant reduction in brain weight and brain length with a concomitant increase in ventricular size. (All findings relate to measurements made after formalin fixation). In addition, the brains of the schizophrenic patients contained significantly more non-specific focal pathology and fibrillary gliosis than the controls. After exclusion of cases with moderate and severe Alzheimer-type change, cerebro-vascular disease and all forms of focal pathology, the structural brain changes (i.e. decrease in brain weight and brain length) continued to distinguish the schizophrenia group from the controls. Furthermore, an analysis of the clinical data showed that the structural brain changes were correlated in the schizophrenic patients with a measurement of pre-morbid function. The findings and their possible aetiological implications have been discussed.

Adult↗
PubMed1990

Temporal lobe asymmetries as the key to the etiology of schizophrenia.

With evidence that determinants of psychosis are present early and influence brain development, and in the absence of a significant environmental contribution, schizophrenia may be regarded as a genetic encephalopathy. Morphological abnormalities are particularly apparent in the temporal lobe and on the left side of the brain, and in a number of studies significant diagnosis x side interactions have been detected. Such interactions suggest an intimate relationship between the disease process and the mechanisms that determine asymmetrical brain development. These mechanisms presumably relate to the human capacity for speech and communication, and they may have played a critical role in the evolution of the human brain. A candidate locus for an asymmetry determinant and the psychosis gene within the exchange region of the sex chromosomes is proposed. Some sex differences in schizophrenia (e.g., with respect to age of onset and brain structure) may relate to subtle differences in the rate of asymmetry development in the two sexes.

Alzheimer Disease↗
PubMed1990

Nature of the genetic contribution to psychotic illness--a continuum viewpoint.

The recurrent psychoses, rather than, as Kraepelin supposed, constituting 2 major entities, manic depressive illness and schizophrenia, as separate diseases, may be distributed along a continuum that extends from unipolar depressive illness through bipolar and schizoaffective psychosis to schizophrenia with increasing severities of defect state. It is proposed that this continuum rests on a genetic base, variations in the form of the gene accounting for variations in form of psychosis. The simplest interpretation of the continuum is that such variation relates to changes at a single genetic locus. Evidence from a postmortem study of brain structure in schizophrenia suggests that this is the gene that determines the development of asymmetries in the human brain, i.e., the cerebral dominance gene or right shift factor of Annett; a possible genomic location is in the pseudoautosomal region of the sex chromosomes.

Bipolar Disorder↗
PubMed1990

The continuum of psychosis and its genetic origins. The sixty-fifth Maudsley lecture.

Attempts to draw a line of genetic demarcation between schizophrenic and affective illnesses have failed. It must be assumed that these diseases are genetically related. A postmortem study has demonstrated that enlargement of the temporal horn of the lateral ventricle in schizophrenia but not in Alzheimer-type dementia is selective to the left side of the brain. This suggest that the gene for psychosis is the 'cerebral dominance gene', the factor that determines the asymmetrical development of the human brain. That the psychosis gene is located in the pseudoautosomal region of the sex chromosomes is consistent with observations that sibling pairs with schizophrenia are more often than would be expected of the same sex and share alleles of a polymorphic marker at the short-arm telomeres of the X and Y chromosomes above chance expectation. That the cerebral dominance gene also is pseudoautosomal is suggested by the pattern of verbal and performance deficits associated with sex-chromosome aneuploidies. The psychoses may thus represent aberrations of a late evolutionary development underlying the recent and rapid increase in brain weight in the transition from Australopithecus through Homo habilis and Homo erectus to Homo sapiens.

Alzheimer Disease↗
PubMed1990

Further investigation of the predictors of outcome following first schizophrenic episodes.

The outcome at two years of patients who were eligible for a study of first schizophrenic episodes was assessed in terms of occupation (n = 237) and in terms of number of days spent as an in-patient from the time of first admission (n = 252), and was related to social, behavioural, mental state and neurological measures during the initial admission. Poor outcome was in general associated with more social withdrawal, inactivity and abnormal social presentation and with more 'neurological soft signs'. Good occupational outcome in patients with a relatively short pre-treatment duration of illness was associated with the prescription of placebo medication during the follow-up period.

Activities of Daily Living↗
PubMed1990

Schizophrenia as a genetic encephalopathy.

Evidence from a number of sources suggests that schizophrenia is primarily genetic in origin: it may be referred to as a "genetic encephalopathy". Intellectual deficits may precede or succeed onset of illness occasionally resulting in a true "dementia praecox". Structural changes in the brain (e.g. ventricular enlargement) are present early and according to a recent postmortem study have a degree of selectivity to the temporal horn on the left side of the brain; this suggests there is an arrest of development of cerebral asymmetry. It is proposed that the disease arises from an anomaly of the genetic determinants of asymmetry (the "cerebral dominance gene") located in the pseudo-autosomal (exchange) region of the sex chromosomes. Psychotic illness may represent a disadvantageous spin-off of the late evolutionary developments that led to the rapid increase in brain capacity in man.

Brain↗
PubMed1989

Diagnosis of Gerstmann-Sträussler syndrome in familial dementia with prion protein gene analysis.

The polymerase chain reaction was used to screen DNA samples from 12 unrelated individuals with various familial dementias and ataxias for mutation in part of the prion protein (PrP) gene, an abnormality that occurs in individuals with the spongiform encephalopathies, Gerstmann-Sträussler syndrome (GSS) and Creutzfeldt-Jakob disease. 2 members of a family in whom GSS was not previously suspected had a 0.15 kb insertion of similar size to that found in another kindred with pathologically proven spongiform encephalopathy. GSS may be more common than is currently realised; PrP gene analysis is potentially useful for diagnosis and genetic counselling in familial dementias and ataxias.

Adult↗
PubMed1989

Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome.

Gerstmann-Sträussler syndrome is a rare familial neurodegenerative condition that is vertically transmitted, in an apparently autosomal dominant way. It can also be horizontally transmitted to non-human primates and rodents through intracerebral inoculation of brain homogenates from patients with the disease. The exact incidence of the syndrome is unknown but is estimated to be between one and ten per hundred million. Patients initially suffer from ataxia or dementia and deteriorate until they die, in one to ten years. Protease-resistant prion protein (PrP) and PrP-immunoreactive amyloid plaques with characteristic morphology accumulate in the brains of these patients. Current diagnostic criteria for Gerstmann-Sträussler syndrome incorporate clinical and neuropathological features, as animal transmission studies can be unreliable. PrP is implicated in the pathogenesis and transmission of the condition and in scrapie, an equivalent animal disease. It was discovered by enriching scrapie-infected hamster brain fractions for infectivity. Because there is compelling evidence that the scrapie isoform of PrP is a necessary component of the infectious particle, it seemed possible that the PrP gene on the short arm of human chromosome 20 in Gerstmann-Sträussler syndrome might be abnormal. We show here that PrP codon 102 is linked to the putative gene for the syndrome in two pedigrees, providing the best evidence to date that this familial condition is inherited despite also being infectious, and that substitution of leucine for proline at PrP codon 102 may lead to the development of Gerstmann-Sträussler syndrome.

Chromosome Mapping↗
PubMed1989

Schizophrenia as an anomaly of development of cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of the disease.

Schizophrenia is associated with structural changes (eg, a mild degree of ventricular enlargement) in the brain, although whether these precede onset of illness or progress with episodes is not established. In a postmortem study, we find that ventricular enlargement affects the posterior and particularly the temporal horn of the lateral cerebral ventricle. By comparison with controls and with patients suffering from Alzheimer-type dementia (in which there is also temporal horn enlargement), the change is highly significantly selective to the left hemisphere. This deviation was not accompanied by an increase in glial cell number (examined chemically by assay of diazepam-binding inhibitor immunoreactivity and microscopically by density of staining with the Holzer technique). The findings are consistent with the view that schizophrenia is a disorder of the genetic mechanisms that control the development of cerebral asymmetry.

Alzheimer Disease↗
PubMed1989

The effects of scopolamine and clonidine upon the performance and learning of a motor skill.

Twenty-eight subjects practised a task involving procedural knowledge in which a moving target has to be followed for two 3-min sessions. They were then randomly allocated to receive an IV injection of 0.4 mg scopolamine, 0.15 mg clonidine or saline. General impairment due to both active treatments was seen 20 min later in significantly decreased tracking performance. Subjects then had to learn a mirror-reversed version of the tracking task. This involved acquiring novel procedural knowledge. Subjects who had either saline or clonidine treatment showed rapid temporary improvements and also considerable permanent learning. Subjects treated with scopolamine, however, showed only slow temporary improvement and little permanent improvement in their performance at this task. This result suggests that a normally functioning cholinergic system is necessary not only for an efficient working memory but also for the long term acquisition of some kinds of procedural knowledge.

Adolescent↗
PubMed1989

The spectrum of structural brain changes in schizophrenia: age of onset as a predictor of cognitive and clinical impairments and their cerebral correlates.

A range of cerebral structures was assessed in a series of 172 CT scans of groups of psychiatric patients (including 101 in-patients with chronic schizophrenia) and related to assessments of clinical state and psychological function. Ventricular indices were increased in patients with schizophrenia by comparison with patients with other psychiatric disorders: brain area, which is modestly positively correlated with ventricular indices, was significantly (P less than 0.01) reduced in patients with schizophrenia. Among in-patients with chronic schizophrenia, measures of increased ventricular size were significantly associated with impaired social behaviour and with movement disorder. Memory for famous names in the distant past (a test of remote memory) was the only psychological test which showed significant associations with indices of ventricular size; this suggests that ventricular enlargement and its psychological sequelae occur relatively early in the disease process. Dichotomization of the sample of schizophrenic patients around the mean age of onset revealed that a range of clinical and psychological functions are significantly more abnormal in those with an early age of onset than in those in whom the onset was later. Early onset cases also perform less well academically and occupationally before illness onset. Within the early onset group some significant correlations between cognitive function and brain area were seen. The findings suggest that: (i) some at least of the structural changes in schizophrenia arise at a time when the brain is still developing; and (ii) age of onset is an important determinant of social and intellectual impairment and is relevant to the relationship between brain structure and cognitive deficits.

Bipolar Disorder↗