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T J Crow

Publications and source records attributed to T J Crow.

At least 91 records · Page 5Linked to original sources
PubMed1997

Anomalous cerebral asymmetry and language processing in schizophrenia.

Reversal or reduction of normal structural cerebral asymmetries may be related to the pathogenesis of schizophrenia, but this relationship remains controversial. We review the literature and describe a further study designed to detect whether anomalous asymmetries are present early in the illness (at the first episode), whether they predict deficits in language processing, and whether they may be related to a genetic predisposition for schizophrenia. Asymmetries of brain widths and segments of the sylvian fissure were assessed in a magnetic resonance imaging study of 87 patients with a first episode of schizophrenia and 52 normal controls. These asymmetries were correlated with specific measures of language processing, memory, and hand skill. An independent group of 14 pairs of siblings with schizophrenia were also evaluated for evidence of heritability to cerebral asymmetries. Width asymmetries were reduced in patients compared with controls in the posterior (p = 0.02) and occipital (p = 0.05) regions. Brain horizontal length, on the other hand, was significantly more asymmetrical in patients (left > right; p = 0.04). For sylvian fissure measurements, asymmetries in controls (left > right) were greatest for the horizontal component; this asymmetry tended to detect differences in patients by comparison with controls (p < 0.06). In a range of tests of language and memory, few significant correlations between performance and cerebral asymmetries were detected either in patients or controls, although patients consistently scored poorer than controls in the majority of tests. In 14 pairs of psychotic siblings, within-pair correlations for the horizontal sylvian fissure asymmetry were significantly greater than between-pair correlations. These findings are consistent with the early presence (possibly genetic) of anomalous cerebral asymmetry. However, the functional correlates of reduced asymmetry remain obscure.

Adult↗
PubMed1997

Temporolimbic or transcallosal connections: where is the primary lesion in schizophrenia and what is its nature?

A critique of the article by Bogerts on the temporolimbic system theory is presented. Schizophrenia is conceived as arising as a component of the diversity of interhemisphric (callosal) connectivity associated with the evolution of language, a process that occurred through a genetic change (the speciation event) that allowed the hemispheres to develop with a degree of independence. Language and psychosis thus have a common evolutionary origin. The anatomical changes can be considered as a boundary component of the anatomical variation that is characteristic of the species.

Biological Evolution↗
PubMed1996

Cerebral lateralization is delayed in children who later develop schizophrenia.

The origins of schizophrenia are obscure. One suggestion is that it represents a component of the genetic variation associated with the establishment of dominance in one or other cerebral hemisphere, a mechanism that has been crucial in the evolution of language. Indices of cerebral hemispheric dominance (hand, foot and eye preference, speed of checking squares) recorded on the 16,980 children in the UK National Child Development Study cohort were examined in relation to psychiatric admission by the age of 28 years. Diagnoses were established by the application of Present State Examination criteria to case notes. Pre-schizophrenic children (n = 34-36) were more likely (p < 0.0003) to be rated by their mothers as ambidextrous at the age of 7 years, and at 11 years were less (p < 0.01) strongly right-handed than their peers in the cohort population on a test of relative hand skill: children who later developed affective psychosis (n = 25) or neurosis (n = 60) did not differ significantly from controls. Delay in establishing dominance in one hemisphere could be the critical factor that predisposes to schizophrenia.

Adolescent↗
PubMed1996

Linkage analyses of schizophrenia to chromosome 6p24-p22: an attempt to replicate.

The present study evaluates evidence for linkage of schizophrenia to chromosome 6p24-p22. An independent sample of 211 families ascertained on the basis of having an affected sib-pair diagnosed with schizophrenia or schizoaffective disorder was assessed with seventeen polymorphic markers spanning a 37cM region. Linkage analysis was performed with parametric and non-parametric methods to test for cosegregation using 4 models of inheritance. Neither two-point nor multipoint non-parametric analyses reached significance at a level less than 0.01 for any markers examined in the region and lod score analyses were not suggestive of linkage. Based on initial findings in the present data set and recently published linkage results, two specific areas were densely covered with markers and tested for linkage disequilibrium. After correcting for multiple comparisons within each locus, no significant deviation from expected allele transmission ratios was observed. The present findings together with the published literature fail to find consistent evidence of a linkage for schizophrenia to a single locus on chromosome 6.

Adult↗
PubMed1996

Analysis of polyglutamine-coding repeats in the TATA-binding protein in different human populations and in patients with schizophrenia and bipolar affective disorder.

A new class of disease (including Huntington disease, Kennedy disease, and spinocerebellar ataxias types 1 and 3) results from abnormal expansions of CAG trinucleotides in the coding regions of genes. In all of these diseases the CAG repeats are thought to be translated into polyglutamine tracts. There is accumulating evidence arguing for CAG trinucleotide expansions as one of the causative disease mutations in schizophrenia and bipolar affective disorder. We and others believe that the TATA-binding protein (TBP) is an important candidate to investigate in these diseases as it contains a highly polymorphic stretch of glutamine codons, which are close to the threshold length where the polyglutamine tracts start to be associated with disease. Thus, we examined the lengths of this polyglutamine repeat in normal unrelated East Anglians, South African Blacks, sub-Saharan Africans mainly from Nigeria, and Asian Indians. We also examined 43 bipolar affective disorder patients and 65 schizophrenic patients. The range of polyglutamine tractlengths that we found in humans was from 26-42 codons. No patients with bipolar affective disorder and schizophrenia had abnormal expansions at this locus.

Africa↗
PubMed1996

Analysis of thirteen trinucleotide repeat loci as candidate genes for schizophrenia and bipolar affective disorder.

A group of diseases are due to abnormal expansions of trinucleotide repeats. These diseases all affect the nervous system. In addition, they manifest the phenomenon of anticipation, in which the disease tends to present at an earlier age or with greater severity in successive generations. Many additional genes with trinucleotide repeats are believed to be expressed in the human brain. As anticipation has been reported in schizophrenia and bipolar affective disorder, we have examined allele distributions of 13 trinucleotide repeat-containing genes, many novel and all expressed in the brain, in genomic DNA from schizophrenic (n = 20-97) and bipolar affective disorder patients (23-30) and controls (n = 43-146). No evidence was obtained to implicate expanded alleles in these 13 genes as causal factors in these diseases.

Base Sequence↗
PubMed1996

Location of the handedness gene on the X and Y chromosomes.

Accumulated data from five handedness surveys show that concordance for sex is slightly but reliably higher among siblings of the same handedness than among those of opposite handedness. This is consistent with Crow's theory that the genetic locus for handedness is in an X-Y homologous region of the sex chromosomes. The small size of the effect is predicted from genetic models in which there is a substantial random component underlying phenotypic left handedness. The findings are relevant to the putative role of cerebral asymmetry in the aetiology of psychosis.

Chromosome Mapping↗
PubMed1996

Obstetric complications in children born to parents with schizophrenia: a meta-analysis of case-control studies.

On the basis of previous findings, we used meta-analyses to consider whether births to parents with schizophrenia have an increased risk of obstetric complications. Meta-analyses were based on published studies satisfying the following selection criteria. The schizophrenic diagnosis could apply to either parent: parents with non-schizophrenic psychoses were not included: only normal controls were accepted. In all, 14 studies provided effect sizes or data from which these could be derived. Studies were identified by data searches through MEDLINE, PSYCLIT and through references of papers relating to the subject. Births to individuals with schizophrenia incur an increased risk of pregnancy and birth complications, low birthweight and poor neonatal condition. However, in each case the effect size is small (mean r = 0.155; 95% CI = 0.057). The risk is greater for mothers with schizophrenia and is not confined to mothers with onset pre-delivery or to the births of the children who become schizophrenic themselves.

Adult↗
PubMed1996

cDNA cloning of a human homologue of the Caenorhabditis elegans cell fate-determining gene mab-21: expression, chromosomal localization and analysis of a highly polymorphic (CAG)n trinucleotide repeat.

The two most consistent features of the diseases caused by trinucleotide repeat expansion-neuropsychiatric symptoms and the phenomenon of genetic anticipation-may be present in forms of dementia, hereditary ataxia, Parkinsonism, bipolar affective disorder, schizophrenia and autism. To identify candidate genes for these disorders, we have screened human brain cDNA libraries for the presence of gene fragments containing polymorphic trinucleotide repeats. Here we report the cDNA cloning of CAGR1, originally detected in a retinal cDNA library. The 2743 bp cDNA contains a 1077 bp open reading frame encoding 359 amino acids. This amino acid sequence is homologous (56% amino acid identify and 81% amino acid conservation) to the Caenorhabditis elegans cell fate-determining protein mab-21. CAGR1 is expressed in several human tissues, most prominently in the cerebellum, as a message of approximately 3.0 kb. The gene was mapped to 13q13, just telomeric to D13S220. A 5'-untranslated CAG trinucleotide repeat is highly polymorphic, with repeat length ranging from six to 31 triplets and a heterozygosity of 87-88% in 684 chromosomes from several human populations. One allele from an individual with an atypical movement disorder and bipolar affective disorder type II contains 46 triplets, 15 triplets longer than any other allele detected. Though insufficient data are available to link the long repeat to this clinical phenotype, an expansion mutation of the CAGR1 repeat can be considered a candidate for the etiology of disorders with anticipation or developmental abnormalities, and particularly any such disorders linked to chromosome 13.

Amino Acid Sequence↗
PubMed1995

Failure to find a chromosome 18 pericentric linkage in families with schizophrenia.

A recent report of a possible linkage of bipolar affective disorder to a pericentric region of chromosome 18 initiated the present investigation to search for a similar linkage in 32 families with schizophrenia. The results of a study using 5 markers mapped to this region show negative lod scores and only weak evidence for any linkage by nonparametric analyses. If the previously reported finding is a true positive linkage for bipolar disorder, then either it is unlikely to be related to the genetics of schizophrenia, or the proportion of families linked to this region is small.

Chromosome Mapping↗
PubMed1995

Childhood precursors of psychosis as clues to its evolutionary origins.

Those who as adults will be admitted to a psychiatric ward with a psychotic illness can be distinguished (on the basis of group differences) from others by their behaviour and academic performance at the ages of 7 and 11 years. Pre-schizophrenic boys are anxious and hostile towards adults and peers at the age of 7 years and show poor concentration. By age 11 years these boys are also rated as depressed, and pre-schizophrenic girls as depressed and withdrawn. Pre-affective psychotic boys show minor changes (for example an increase in hostility and restlessness) at age 7 years, although these features are not obvious at age 11 years. Abnormalities that in some respects resemble those in pre-schizophrenic boys are present at age 11 years in a group of females who will be admitted to psychiatric units with non-psychotic diagnoses by the age of 28 years. Academic impairments (including speech and reading difficulties) at ages 7, 11 and 16 years are more severe in pre-schizophrenics than in the other groups. Schizophrenics-to-be are slow to develop continence and show poor coordination and vision at age 7 years, and are rated clumsy at age 16 years. Psychosis reflects a disturbance of aspects of central nervous system function that are time-dependent and in certain respects gender specific. It is argued that the psychoses represent extremes of variation in a gene (or genes) that differs between sexes and controls the timing of development of the two cerebral hemispheres.(ABSTRACT TRUNCATED AT 250 WORDS)

Achievement↗
PubMed1995

A continuum of psychosis, one human gene, and not much else--the case for homogeneity.

The contention of this paper is that psychoses are not a collection of separate and unrelated diseases, but a set of diverse expressions of a single underlying entity. It will be argued that there is a basic homogeneity of pathogenesis, that there are not multiple predisposing genes but a single gene that is associated with significant diversity. Therefore the problem is a unitary one. The challenge is to identify the nature and function of the gene. It will be argued that the gene is that by which homo sapiens has separated from other primate species, and that the diversity arises from selective pressures which continue to act on this specifically human gene.

Animals↗