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T J Crow

Publications and source records attributed to T J Crow.

At least 37 records · Page 2Linked to original sources
PubMed2000

No evidence for a parent-of-origin effect detected in the pattern of inheritance of schizophrenia.

BACKGROUND: Schizophrenia is a complex genetic disorder with no clear pattern of inheritance. Epigenetic modification of genes may thus play a role in its transmission. METHODS: In our study, 439 families with at least two ill siblings with schizophrenia (208 with unilineal transmission) were examined for evidence of a parent-of-origin effect (e.g., evidence of parental imprinting on the familial transmission of schizophrenia). RESULTS: No significant difference in the prevalence of maternal compared with paternal transmission was found. In addition, affected male subjects did not differ from affected female subjects in the proportion of their offspring diagnosed with schizophrenia. CONCLUSIONS: Although the transmission of schizophrenia may be influenced by epigenetic events, our study fails to find evidence that one epigenetic mechanism, a parent-of-origin imprinting effect, determines whether an individual expresses the illness.

Adult↗
PubMed2000

Phylogenetic analysis of retroposon family as exemplified on human chromosome 13: further evidence for recent proliferation.

The retroposon SINE-R.C2 was first identified as a human-specific insertion in the complement C2 gene. In our previous study, SINE-R type retroposons, derived from the endogenous retrovirus HERV-K family, have been found to be hominoid specific. In this report on human chromosome 13, we identified eighteen new SINE-R retroposons resembling those we have previously reported on the sex chromosomes and on chromosomes 7 and 17. Phylogenetic analysis using the neighbor-joining method revealed that four SINE-R retroposons (13-16, 21, 23, 25) on chromosome 13 were closely related to the human-specific retroposon SINE-R.C2, with a high degree of sequence homology (95-97%). Such elements differ from the HERV-K10. LTR sequence from which they are derived in being deleted for the promoter region. Therefore while the evidence adds to the case that some classes of SINE-R element have continued to proliferate in hominid and hominoid evolution and may, as in the case of Fukuyama type muscular dystrophy, be a cause of insertional mutagenesis, they are less likely than the HERV-K10 LTR to have a positive effect on host gene activity.

Chromosomes, Human, Pair 13↗
PubMed2000

Failure to establish linkage on the X chromosome in 301 families with schizophrenia or schizoaffective disorder.

The hypothesis that a gene for susceptibility to psychosis (specifically in the X-Y homologous class) is located on the sex chromosomes has been proposed. Such a gene would account for the excess of sex chromosome anomalous males and females in populations of patients with psychosis, a tendency towards concordance by sex within families, and sex differences associated with psychosis and its underlying brain pathology. In earlier studies we observed small positive LOD scores in Xp11, and in a more recent and larger cohort of 178 sibling pairs, a peak multipoint nonparametric LOD score of 1. 55 at the locus DXS8032 in Xq21. The present study with a new set of markers extended the cohort to 301 ill sibling pairs and their parents. Despite the increase in sample size, the LOD score did not increase. A peak NPL of 1.55 was observed at the locus DXS1068 in proximal Xp, a region remote from the previous report. Separating families into those who were more likely to have X chromosome inheritance (maternal with no male to male transmission) did not yield stronger findings. In spite of the evidence that psychosis is related to a sex-dependent dimension of cerebral asymmetry, it is concluded that no consistent linkage of schizophrenia to the X chromosome can be demonstrated. In the context of the general failure of replication of linkage in psychosis, the possibility that the genetic predisposition to psychosis is contributed to by epigenetic modification rather than variations in the nucleotide sequence has to be considered.

Chromosome Mapping↗
PubMed2000

Lack of evidence for linkage to chromosomes 13 and 8 for schizophrenia and schizoaffective disorder.

A previous report [Blouin et al., 1998: Nat Genet 20:70-73] suggesting linkage to chromosomes 13q32 and 8p21 in families with schizophrenia led us to investigate these regions in a large set of 301 multiplex families with schizophrenia. Multipoint analyses failed to reveal evidence for linkage to any portion of chromosome 13, while only a weakly positive score was present on 8p using the identical marker reported in the earlier report. Failure to confirm the Blouin et al claims in a substantially larger cohort adds emphasis to the inconsistency of the findings concerning linkage in schizophrenia. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:235-239, 2000.

Chromosomes, Human, Pair 13↗
PubMed2000

Schizophrenia as the price that homo sapiens pays for language: a resolution of the central paradox in the origin of the species.

The central paradox of schizophrenia is that the condition, apparently genetic in origin, persists in spite of a substantial fecundity disadvantage. The hypothesis is proposed that the predisposition to schizophrenia is a component of Homo sapiens-specific variation associated with the capacity for language. A genetic change (the 'speciation event', predicted to be related to the Xq21.3 to Yp chromosomal transposition that separates Homo sapiens from the great apes) allowed the hemispheres to develop with a 'cerebral torque', reflected particularly in association cortex, from right frontal to left occipital. Variations in the dimension of lateralization are associated with differences in the rate at which verbal and non-verbal ability develops. The nuclear symptoms of schizophrenia can be understood as a failure to establish dominance for a key component - the phonological sequence - of language in one hemisphere, with consequent disruption of the mechanism of 'indexicality' that allows the speaker to distinguish his thoughts from the speech output that he generates and the speech input that he receives and decodes from others.

Animals↗
PubMed2000

Anomalous asymmetry of fusiform and parahippocampal gyrus gray matter in schizophrenia: A postmortem study.

OBJECTIVE: Anomalies of structure and asymmetry of the parahippocampal gyrus (origin of the perforant path input to the hippocampal formation in the medial temporal lobe) have been shown in some postmortem studies of schizophrenia, but previous studies have not included the fusiform gyrus (which may have a role in facial recognition and naming), adjacent to the parahippocampal gyrus on the ventral occipitotemporal surface. METHOD: The volumes of gray matter in the left and right parahippocampal and fusiform gyri were assessed with a stereological point-counting technique in the temporal lobes from formalin-fixed brains of 27 comparison subjects and 31 patients with schizophrenia. Age was a covariate and gender was a factor in the analysis. RESULTS: In relation to the comparison subjects, the schizophrenic patients (both sexes) had lower volumes of both the parahippocampal and fusiform gyri on the left side. For both structures a left-greater-than-right volume asymmetry was present in the comparison subjects, but this asymmetry was reversed in the parahippocampal and fusiform gyri of the schizophrenic patients. A sex difference was present with respect to age at onset-degree of anomaly of asymmetry for both gyri increased with age at onset in men but not in women. CONCLUSIONS: The findings add substance to the view that the sex-related dimension of symmetry/asymmetry is integral to the disease process in schizophrenia and draw attention to the fusiform gyrus as a structure of particular interest in relation to disturbances of identification and naming in psychosis.

Adult↗
PubMed2000

Factor structure and familiality of first-rank symptoms in sibling pairs with schizophrenia and schizoaffective disorder.

BACKGROUND: Since their introduction as diagnostic criteria by Schneider in 1937, nuclear symptoms have played a key role in concepts of schizophrenia, but their relationship to each other and to genetic predisposition has been unclear. AIMS: To ascertain the factor structure and familiality of nuclear symptoms. METHODS: Nuclear (Schneiderian) symptoms were extracted from case notes and interviews in a study of 103 sibling pairs with DSM-III-R schizophrenia or schizoaffective disorder. RESULTS: Principal components analysis demonstrated two major factors: one, accounting for about 50% of the variance, groups thought withdrawal, insertion and broadcasting, with delusions of control; and the second, accounting for < 20% of the variance, groups together third-person voices, thought echo and running commentary. Factor I was significantly correlated within sibling pairs. CONCLUSIONS: The correlation within sibling pairs suggests that, contrary to the conclusion of some previous studies, some nuclear symptoms do show a degree of familiality and therefore perhaps heritability.

Adolescent↗
PubMed2000

No association between breast-feeding and adult psychosis in two national birth cohorts.

BACKGROUND: It has been proposed that breast-feeding might have a protective effect against the development of adult schizophrenia. AIMS: To test this hypothesis. METHOD: Using prospective data from two UK national birth cohorts, the feeding histories of those who later developed schizophrenia were compared with the remaining population at risk. Analyses in each cohort were considered to be independent tests of the hypothesis. RESULTS: There were no differences in feeding histories. In the 1946 birth cohort (n = 4447) 30 cases of DSM-III-R schizophrenia arose by age 43; 24.1% of cases v. 23.6% of controls were entirely bottle-fed; 17.3% v. 12.3% were breast-fed for under 1 month; 58.6% v. 64.1% were breast-fed beyond 1 month. In the 1958 cohort (n = 18,856), 40 cases of CATEGO nuclear schizophrenia arose by age 28; 24.1% of cases v. 31.7% of controls were entirely bottle-fed; 27.6% v. 24.9% were breast-fed for under 1 month; 48.3% v. 43.4% were breast-fed beyond 1 month. CONCLUSIONS: These findings provide no evidence of any effect of breast-feeding in protecting against the risk of later schizophrenia.

Adolescent↗
PubMed2000

Phylogenetic analysis of a retroposon family as represented on the human X chromosome.

SINE-R elements constitute a class of retroposons derived from the long terminal repeat (LTR) of the human endogenous retrovirus HERV-K family that are present in hominoid primates and active in the human genome. In an investigation of the X chromosome, we identified twenty-five SINE-R elements with between 89.6 and 97.7% homology with the SINE-R.C2 element that is human specific, originally identified in the gene for the C2 component of complement. SINE-R.C2 and a sequence HS307 that we previously identified in a region of Xq21.3 that has a recently created homology with a 4 Mb block in Yp11.2 are amongst the group of elements that have diverged furthest from the parent HERV-K10 sequence. The sequence on the X chromosome resemble those that we previously described on chromosomes 7 and 17 and the Y chromosome, with a similar range of variation. Phylogenetic analysis from the retroposon family including those of African great apes using the neighbor-joining method suggests that the SINE-R retroposon family have evolved independently during primate evolution. Further investigation of SINE-R elements on the sex chromosomes, particularly in recently created regions of X-Y homology, may cast light on the timing of the retroposition process and its possible relevance to recent evolutionary change.

Animals↗
PubMed1999

Is the course of brain development in schizophrenia delayed? Evidence from onsets in adolescence.

A degree of ventricular enlargement, together with a reduction of total cortical mass and loss of asymmetry is reported in schizophrenia, but the meaning is obscure. These changes may reflect an anomaly of brain development. Brain structure was assessed on a 1.5-Tesla MRI scan in a series of 29 adolescents at the time of a first episode of schizophrenia and compared with 15 adolescents with other serious psychiatric disturbance (mostly psychotic) and 20 normal adolescent controls. The age at scan ranged between 13 and 20 years. In the adolescents with a diagnosis of schizophrenia, total brain volume increased with age in a way that differed significantly (p=0.007) from that seen in patients with other psychiatric disturbance and normal controls. Thus, brain growth, as assessed by this index, had reached a plateau in the control group by the age of 13 years, but this was not true of patients with schizophrenia. The measure that most clearly distinguished the groups (p<0.001 after co-varying for height and sex) was the volume of the left lateral ventricle the ventricle was significantly larger in patients with schizophrenic illness, and ventricular size increased with age to a greater extent in the patient group, although not significantly so, than in normal controls. Thus, aspects of brain growth are delayed in patients with early onset schizophrenia, and the greatest severity of illness is reflected in a component of growth that is lateralized to the dominant hemisphere. Individuals who develop serious psychiatric illness, including schizophrenia, represent a fraction of the population in whom a component of the relative development of the cerebral hemispheres occurs late.

Adolescent↗
PubMed1999

Commentary on Annett, Yeo et al., Klar, Saugstad and Orr: cerebral asymmetry, language and psychosis--the case for a Homo sapiens-specific sex-linked gene for brain growth.

Annett, Yeo et al. and Klar have each proposed theories that relate the genetics of cerebral lateralization to predisposition to psychosis. These theories are considered in relation to the central paradox that psychosis is associated with a substantial biological disadvantage. Annett's heterozygote advantage hypothesis critically identified lateralization as a major determinant of ability, but it appears that what is inherited is degrees (as suggested by Yeo et al.) rather than (or as well as) direction of lateralization. Relative hand skill has been shown (Crow, T.J., Crow, L.R., Done, D.J., Leask, S.J., 1998. Relative hand skill predicts academic ability: global deficits at the point of hemispheric indecision. Neuropsychologia 36, 1275-1282.) to be a powerful predictor (interacting with sex) of academic ability but the greatest region of vulnerability (that includes reading disability and predisposition to psychosis) is close to the point of equal hand skill ('hemispheric indecision'). In contrast with Annett's single locus, Yeo's polygenic and Klar's strand-segregation hypotheses, each of which postulates an autosomal locus or loci, the hypothesis of a single gene for asymmetry located in a sex-specific region of homology on both X and Y chromosomes can account for sex differences, as observed in age of onset, and premorbid precursors of psychosis, as well as differences in the general population in relation to degrees of hand skill, verbal ability and cerebral asymmetry. The evolutionarily recent transposition to, and subsequent paracentric inversion in, the Y chromosome short arm of a 4-Mb block from Xq21.3 (the proximal long arm of the X) are candidates for speciation events in the lineage that led to Homo sapiens. A gene associated with a range of variation (that may be due to a high mutation site, or perhaps to epigenetic modification) on the Y that overlaps with, but differs quantitatively from, that on the X may explain the sex differences associated with psychosis, and may be relevant to its persistence. Such a gene could be the principal determinant in Man of the rate of brain growth, as suggested by Saugstad and by the findings of a recent study of adolescent onset psychosis (James, A., Crow, T.J., Renowden, S., Wardell, M., Smith, D.M., Anslow, P., in press. Is the course of brain development in schizophrenia delayed? Evidence from onsets in adolescence. Schizophr. Res.).

Biological Evolution↗
PubMed1999

SINE-R.C2 (a Homo sapiens specific retroposon) is homologous to CDNA from postmortem brain in schizophrenia and to two loci in the Xq21.3/Yp block linked to handedness and psychosis.

We investigated the retroviral/retroposon hypothesis of schizophrenia by generating sequences with PCR primers based on a retroviral sequence recovered by Yee et al. [1998: Schizophr Res 29:92] from a cDNA library from postmortem brain tissue from an individual with psychosis in a genomic region (Xq21.3) that has been tentatively linked to schizophrenia and schizoaffective disorder by Laval et al. [1998: Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:420-427]. Within the block of homology with Yp that was generated by a transposition between the chimpanzee and Homo sapiens we find two sequences, HS307 and HS408, with a high degree of homology to but not identity with the schizophrenic brain cDNA. The closest match of these three sequences is to a family of retroposons, that has evolved from the HERV-K family of endogenous retroviruses, some members of which (e.g., SINE-R.C2) appear to be specific to the human genome. This element has been reported as a cause of Fukuyama-type muscular dystrophy [Kobayashi et al., 1998: Nature 394:388-392]. Such retroposons, as agents of change in the human genome, provide a strategy for investigating pathogenesis. On account of their genomic location in a region that has been subject to change in the course of hominid evolution, and that may have a relationship to psychosis and/or cerebral asymmetry, we conclude that these particular insertions deserve further investigation.

Animals↗