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T J Crow

Publications and source records attributed to T J Crow.

At least 73 records · Page 4Linked to original sources
PubMed1998

Evidence for linkage to psychosis and cerebral asymmetry (relative hand skill) on the X chromosome.

The hypothesis that psychosis arises as a part of the genetic diversity associated with the evolution of language generates the prediction that illness will be linked to a gene determining cerebral asymmetry, which, from the evidence of sex chromosome aneuploidies, is present in homologous form on the X and Y chromosomes. We investigated evidence of linkage to markers on the X chromosome in 1) 178 families multiply affected with schizophrenia or schizoaffective disorder with a series of 16 markers spanning the centromere (study 1), and 2) 180 pairs of left-handed brothers with 14 markers spanning the whole chromosome (study 2). In study 1, excess allele-sharing was observed in brother-brother pairs (but not brother-sister or a small sample of sister-sister pairs) over a region of approximately 20 cM, with a maximum LOD score of 1.5 at DXS991. In study 2, an association between allele-sharing and degree of left-handedness was observed extending over approximately 60 cM, with a maximum lod score of 2.8 at DXS990 (approximately 20 cM from DXS991). Within the overlap of allele-sharing is located a block in Xq21 that transposed to the Y chromosome in recent hominid evolution and is now represented as two segments on Yp. In one of two XX males with psychosis we found that the breakpoint on the Y is located within the distal region of homology to the block in Xq21. These findings are consistent with the hypothesis that an X-Y homologous determinant of cerebral asymmetry carries the variation that contributes to the predisposition to psychotic illness.

Female↗
PubMed1998

Familial associations of subsyndromes of psychosis in affected sibling pairs with schizophrenia and schizoaffective disorder.

Attempts to describe the clinical heterogeneity of schizophrenia have consisted of categorical subtyping and a dimensional approach using factor analysis. The latter has yielded three dimensions or subsyndromes: positive, negative and disorganisation. The aim of this study is to explore to what degree these subsyndromes are correlated within 114 sibling pairs (185 individuals) with DSM-III-R schizophrenia or schizo-affective disorder who were assessed for the lifetime presence or absence of the positive, negative, affective and disorganisation subsyndromes. Ratings were based on the core symptoms of each subsyndrome using a modified Krawieka scale. First rank symptoms were also included in the analysis. Coincidence was assessed by application of the binomial theorem to the frequency of occurrence of subsyndromes in this set of siblings. The disorganisation subsyndrome was shared above chance expectation (chi2=9.15, P < 0.01 for all sibling pairs). The significant results for the disorganisation subsyndrome suggest that it may be a suitable phenotypic marker for genetic linkage studies.

Adult↗
PubMed1998

Absence of basal ganglia amino acid neuron deficits in schizophrenia in three collections of brains.

Amino acid (glutamatergic, GABAergic) neuron deficiency theories of schizophrenia offer plausible explanations of pathogenesis. However, reports of disease-related reductions in amino acid synthesizing enzymes in post-mortem brains are contradictory. We measured neuronal uptake sites for gamma-aminobutyric acid (GABA; [3H]nipecotic acid binding) and nerve terminal/glial uptake sites for L-glutamate (D-[3H aspartate binding) in three independent groups of post-mortem brains from patients with schizophrenia and control subjects. Measurements were also made of the phencyclidine site of the glutamate N-methyl-D-aspartate (NMDA) receptor. Samples from patients showed no reductions in the binding of [3H]nipecotic acid or D-[3H]aspartate in caudate, putamen or globus pallidus. On the contrary, some increased binding of both ligands was observed in patients in many comparisons with controls. There were no clear-cut changes in NMDA receptor binding. The most consistent change in the brain sets was increased [3H]nipecotic acid binding in caudate-putamen. This could be due to neuroleptic treatment. The findings produce no evidence that schizophrenia involves major loss of GABA neuron terminals in the basal ganglia or losses of corticostriatal glutamatergic projections.

ATP-Binding Cassette Transporters↗
PubMed1998

Schizophrenia as a transcallosal misconnection syndrome.

Schizophrenic symptoms are conceived as arising from inter-individual variability in the distribution of those fibres that connect asymmetrical regions of the hemispheres related to language. Language (a bihemispheric phenomenon) arose as a result of a genetic change that allowed the two hemispheres to develop with a degree of independence. One component, the phonological output sequence, became localised to the dominant hemisphere, interacting through the corpus callosum with other component functions, including the associated meanings, in the non-dominant hemisphere. Nuclear symptoms are a consequence of failure of segregation of these two functions. This failure is associated with abnormal connectivity between the hemispheres and relates particularly to those regions that are late developing and differ between the sexes.

Biological Evolution↗
PubMed1998

Relative hand skill predicts academic ability: global deficits at the point of hemispheric indecision.

Population variation in handedness (a correlate of cerebral dominance for language) is in part genetic and, it has been suggested, its persistence represents a balanced polymorphism with respect to cognitive ability. This hypothesis was tested in a sample of 12,770 individuals in a UK national cohort (the National Child Development Study) by assessing relative hand skill (in a square checking task) as a predictor of verbal, non-verbal, and mathematical ability and reading comprehension at the age of 11 years. Whereas some modest decrements were present in extreme right handers the most substantial deficits in ability were seen close to the point of equal hand skill ('hemispheric indecision'). For verbal ability females performed better than males, but the relationship to relative hand skill was closely similar for the two sexes; for reading comprehension males close to the point of equal hand skill showed greater impairments than females. Analysed by writing hand the relationship of ability to hand skill appeared symmetrical about the point of 'hemispheric indecision'. The variation associated with degrees of dominance may reflect the operation of continuing selection on the gene (postulated to be X-Y linked) by which language evolved and speciation occurred.

Achievement↗
PubMed1998

Linguistic performance in children who develop schizophrenia in adult life. Evidence for normal syntactic ability.

BACKGROUND: Less syntactically complex speech in patients with schizophrenia has been thought to represent a premorbid dysfunction, of possible prognostic value and indicative of a neurodevelopmental origin for schizophrenia. METHOD: Narratives written at age 11 by children who then developed psychiatric disorders in adult life (using PSE CATEGO diagnoses), especially schizophrenia, were compared with matched controls on syntactic complexity, syntactic maturity, grammatical deviance and spelling ability. RESULTS: Children who later developed either schizophrenia, affective psychosis or a neurotic type of disorder in adulthood did not differ from normal controls on any of the measures of syntactic production, grammatical errors or spelling. CONCLUSIONS: It is probable that previous reports of reduced syntactic complexity in schizophrenic speech are a consequence of being in a psychotic state and do not represent a premorbid deficit.

Adolescent↗
PubMed1998

Nuclear schizophrenic symptoms as a window on the relationship between thought and speech.

BACKGROUND: Symptoms of schizophrenia known as 'nuclear' or 'first-rank' are found in all populations. The genetic variation that gives rise to them must be as old as modern Homo sapiens. METHOD: The hypothesis was formulated that language evolved, under constraints on callosal transmission, by a process of hemispheric specialisation. One component, the phonological output sequence, became localised to the dominant hemisphere whereas its associations (the signifieds) were lateralised in part to the non-dominant hemisphere. Concepts ('thoughts') are translated through a bi-hemispheric interaction into phonemes ('speech') by the speaker in frontal association areas, and decoded back into concepts ('meanings') by the hearer in occipitotemporo-parietal association areas. RESULTS: The first-rank symptoms demonstrate that an integral component is a system of 'indexicality' that distinguishes those phonemic signals generated by the hearer, from his own thoughts, and from signals that he receives from an interlocutor. CONCLUSIONS: Language, as Buehler proposed, is cast in a coordinate system orientated at its origin, in the dominant hemisphere, to the self of the speaker. Thus conceived, the phenomena of the illness called schizophrenia are key to the neural organisation of the human characteristic of language.

Brain Diseases↗
PubMed1997

Is schizophrenia the price that Homo sapiens pays for language?

The dichotomy between schizophrenia and manic-depressive illness is, as E. Kraepelin suspected, flawed; no unequivocal separation can be achieved. There are no categories of psychosis, but only continua of variation. However, the definition of nuclear symptoms by K. Schneider reveals the fundamental characteristics of the core syndrome--it is independent of the environment and constant in incidence across populations that have been separated for thousands of years. The associated genetic variation must be as old as Homo sapiens and represent a component of diversity that crosses the population as a whole. The fecundity disadvantage that accompanies the syndrome requires a balance in a substantial and universal advantage; this advantage, it is proposed, is the speciation characteristic of language; language and psychosis have a common evolutionary origin. Language, it is suggested, originated in a critical change on the sex chromosomes (the 'speciation event'--the genetic change that defined the species) occurring in East Africa between 100 and 250 thousand years ago that allowed the two hemispheres to develop with a degree of independence. Language can be understood as bi-hemispheric with one component function--a linear output sequence--confined to the dominant hemisphere--and a second--parallel distributed sampling occurring mainly in the non-dominant hemisphere. This mechanism provides an account of the generativity of language. The significance of nuclear symptoms is that these reflect a breakdown of bi-hemispheric coordination of language, perhaps specifically of the process of 'indexicalisation' (the distinction between 'I' and 'you') of self- versus other-generated references. Nuclear symptoms can be described as 'language at the end of its tether'; the phenomena and population characteristics of the nuclear syndrome of schizophrenia thus yield clues to the origin of the species.

Biological Evolution↗
PubMed1997

A linkage study of schizophrenia to markers within Xp11 near the MAOB gene.

A sex chromosome locus for psychosis has been considered on the basis of some sex differences in genetic risk and expression of illness, and an association with X-chromosome anomalies. Previous molecular genetic studies produced weak evidence for linkage of schizophrenia to the proximal short arm of the X-chromosome, while some other regions were not ruled out. Here we report an attempt to expand the Xp findings in: (i) a multicenter collaboration focusing on 92 families with a maternal pattern of inheritance (Study I), and (ii) an independent sample of 34 families unselected for parental mode of transmission (Study II). In the multicenter study, a parametric analysis resulted in positive lod scores (highest of 1.97 for dominant and 1.19 for recessive inheritance at a theta of 0.20) for locus DXS7, with scores below 0.50 for other markers in this region (MAOB, DXS228, and ARAF1). Significant allele sharing among affected sibling pairs was present at DXS7. In the second study, positive lod scores were observed at MAOB (highest of 2.16 at a theta of 0.05 for dominant and 1.64 at a theta of 0.00 for recessive models) and ALAS2 (the highest of 1.36 at a theta of 0.05 for a recessive model), with significant allele sharing (P = 0.003 and 0.01, respectively) at these two loci. These five markers are mapped within a small region of Xp11. Thus, although substantial regions of the X-chromosome have been investigated without evidence for linkage being found, a locus predisposing to schizophrenia in the proximal short arm of the X-chromosome is not excluded.

Chromosome Mapping↗
PubMed1997

How far does the brain lateralize?: an unbiased method for determining the optimum degree of hemispheric specialization.

The relationship between measures (of size or function) on one side of the brain, in relation to the difference between the two sides on that measure, are important components of theories of hemispheric asymmetry. For example, it has been concluded that increasing lateralization (e.g., of hand skill or planum temporale area) occurs at the expense of the non-dominant hemisphere. Here it is demonstrated that such relationships could merely be a necessary consequence of relating components of a laterality index to the index (L - R)/(L + R) itself, or indeed to L - R. An alternative approach (using random data to exemplify the null hypothesis) is presented together with an application to data on hand skill from 12,782 11-year-olds in a cohort study. This demonstrates a symmetry hitherto undocumented of maximal hand skill in left and right hands in left- and right-hand writers respectively, the point of the maximum falling short of the population mean for relative hand skill in either case. If degrees of laterality are what is genetically determined, this suggests that selection is present for a function (perhaps language) associated with a greater magnitude of lateralization than is represented by hand skill.

Child↗
PubMed1997

Schizophrenia as failure of hemispheric dominance for language.

Schizophrenic illnesses occur with approximately the same incidence in all human populations with a characteristic distribution (slightly earlier in males) of ages of onset. Given that the predisposition (which presumably is genetic) is associated with a procreative disadvantage why do such illnesses persist? Here it is suggested that these conditions are a manifestation of genetic diversity in the evolution of the specifically human characteristic of language, an innovation that has occurred by a process of progressive hemispheric specialization-the establishment of dominance for some critical component of language in one or the other hemisphere. Individuals who develop schizophrenic symptoms show lesser anatomical and functional asymmetries than the population as a whole; such symptoms may reflect 'dominance failure' for language.

Dominance, Cerebral↗