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T J Crow

Publications and source records attributed to T J Crow.

At least 109 records · Page 6Linked to original sources
PubMed1995

Affective illness and schizophrenia in families with multiple schizophrenic members: independent illnesses or variant gene(s)?

Affective disorder occurs in some families with schizophrenia, and schizophrenic patients often describe concurrent episode(s) of depression that may lead them to be diagnosed schizoaffective. The present study examines the pattern of affective disorder in families with two or more members with schizophrenia or schizoaffective disorder. We find that affective disorders are more frequently inherited from the same parental side of the family as schizophrenia-like psychosis. When unipolar, it more often is expressed in female than male relatives (particularly mothers), and when bipolar it is more likely in males. In contrast, schizophrenia with and without depression is equally prevalent in both sexes. Unipolar illness was more common in relatives of schizophrenics whose illnesses are characterized by recurrent episodes of depression than in those whose are not. These data are consistent with the hypothesis that the same genes could contribute to susceptibility to both schizophrenia and affective disorder in some families, and that sex and phenotypic expression are in some way related. However, the phenomenon of high rates of depression in mothers of schizophrenic patients needs explanation.

Adult↗
PubMed1995

A theory of the evolutionary origins of psychosis.

The incidence and typical symptoms of schizophrenia are similar in diverse human populations; it is likely that the same is true for manic-depressive illnesses. Relative constancy of incidence over time and place (referred to as the 'anthropo-parity principle') and absence of evidence for environmental causation suggest that these disorders are genetic in origin and in some way characteristic of the human condition. Continued high prevalence in the face of a fertility disadvantage requires explanation--why do the genes persist and what is their function? It is proposed that the origins of psychosis are closely linked to the evolution of the human brain. The capacity for language evolved by the process of hemispheric specialisation, a gene for asymmetry (the 'right shift factor' or cerebral dominance gene) playing a critical role. This gene, it is suggested, is represented in homologous form on the X and Y chromosomes and has been subject to sexual selection. Such a locus could explain sex differences in cerebral asymmetry, and in age of onset and outcome of psychosis.

Age of Onset↗
PubMed1995

Brain changes and negative symptoms in schizophrenia.

Negative symptoms (and cognitive impairments) in schizophrenia are a correlate of early onset and poor outcome. It is plausible that they are related to an arrest of brain development, for which there is now considerable evidence, but the precise relationship is elusive. In one post-mortem study negative symptoms were related to a reduction in brain length and in an MRI study to an asymmetry of sulcal CSF. It is proposed that the phenomena of psychosis (including negative symptoms) can be understood as part of the diversity of human personality structure generated by a process of sexual selection acting on a sexual dimorphism for cerebral asymmetry.

Age of Onset↗
PubMed1995

Antecedents of schizophrenia and affective illness. Obstetric complications.

BACKGROUND: This exploratory study seeks to generate new hypotheses about the relationship between obstetric complications and schizophrenia. METHOD: The British Perinatal Mortality Survey represents 98% of all births during one week in March 1958 in Great Britain. Present State Examination (PSE), Catego diagnoses of narrowly defined schizophrenia (n = 49), broadly defined schizophrenia (n = 79), affective psychosis (n = 44) and neurosis (n = 93) were derived from case notes for all cohort members. The remainder of the cohort, surviving the perinatal period, acted as controls (n = 16 812). Variables in the British Perinatal Mortality Survey were grouped into five categories: the physique/lifestyle of the mother (including demographic characteristics), her obstetric history, the current pregnancy, the delivery and the condition of the baby. RESULTS: There were 7/17 significant differences in maternal physique/lifestyle and obstetric history between the births of schizophrenics and controls, compared to 4/40 comparisons of somatic variables relating to pregnancy, birth and the condition of the baby. This compares with 4/17 and 7/40 for affective psychotics and a total of 4/57 differences for all categories of variables when neurotics were contrasted with controls. CONCLUSIONS: The purported increased risk of obstetric complications in schizophrenics may result from the physique/lifestyle of their mothers.

Affective Disorders, Psychotic↗
PubMed1995

A Darwinian approach to the origins of psychosis.

BACKGROUND: The onset of psychotic illness in the reproductive phase of life with a decrease in fecundity (and approximately constant incidence across populations) requires an evolutionary explanation. What is the survival value of the predisposing gene or genes? METHOD: Evolutionary theories, including the author's, are reviewed and critically compared. RESULTS: Some theories (e.g. Huxley et al, 1964) postulate an advantage outside the nervous system: such theories fail to explain either the characteristic age distribution or constant incidence. More plausible are theories that relate the advantage to diversity of personality structure or social ability, or even to general intelligence, i.e. to the areas of function in which the phenomena of psychosis arise. CONCLUSIONS: It is argued that psychosis arises as the boundary of a distribution of variation in cerebral structure generated in the course of hominid evolution. Language played a central role, with the critical changes taking place on the basis of a mutation that allowed the two cerebral hemispheres to develop with a degree of independence. Sexual selection (differing criteria in females and males in choosing a mate) acting on this genetic innovation has generated a dimension of competence in social interaction in relation to which there has been a progressive increase in cerebral size by delayed maturation (neoteny). A sexual dimorphism in cerebral asymmetry and the sex difference in age of onset of psychosis can be parsimoniously explained if a gene regulating the relative growth of the two hemispheres is X-Y homologous.

Biological Evolution↗
PubMed1995

Aetiology of schizophrenia: an evolutionary theory.

It is proposed that schizophrenia is a purely genetic condition that arises as a component of the variation generated in the speciation of Homo sapiens through the evolution of the faculty of language. A critical genetic change on the X and Y chromosomes allowed the two hemispheres to develop with a degree of independence. Thus Man's particular capacity for communication has evolved by a process of increasing hemispheric specialization on the basis of persisting diversity for the asymmetry ('right-shift)' factor. Sex differences in age of onset of psychosis, premorbid precursors and outcome are accounted for in terms of a mean difference between the sexes in cerebral asymmetry. The ultimate cause of this difference is the mechanism of sexual selection acting to retain different ranges of variation of the gene on the X and Y chromosomes. These ranges are expressed in terms of variation in hemispheric specialization and psychological function, a boundary of which represents the predisposition of psychosis. The hypothesis is developmental in the sense that the relevant gene has an influence in development and affects a critical aspect of higher nervous system function. But the key evolutionary process of selection of gene variants occurs late, by the mechanism of mate choice.

Humans↗
PubMed1994

Childhood antecedents of schizophrenia and affective illness: social adjustment at ages 7 and 11.

OBJECTIVE: To investigate the social adjustment in childhood of people who as adults have psychiatric disorders. DESIGN: Subjects in a prospectively followed up cohort (the national child development study) who had been admitted as adults to psychiatric hospitals were compared with the rest of the cohort on ratings of social behaviour made by teachers at the ages of 7 and 11 years. SUBJECTS: 40 adult patients with schizophrenic illnesses, 35 with affective psychoses, and 79 with neurotic illness who had been admitted for psychiatric reasons by the age of 28. 1914 randomly selected members of the cohort who had never been admitted for psychiatric treatment. MAIN OUTCOME MEASURES: Overall scores and scores for overreaction (externalising behaviour) and underreaction (internalising behaviour) with the Bristol social adjustment guide at ages 7 and 11. RESULTS: At the age of 7 children who developed schizophrenia were rated by their teachers as manifesting more social maladjustment than controls (overall score 4.3 (SD 2.4) v 3.1 (2.0); P < 0.01). This was more apparent in the boys (5 (2.6)) than the girls (3.4 (1.8)) and related to overreactive rather than underreactive behaviour. At both ages prepsychotic (affective) children differed little from normal controls. By the age of 11 preneurotic children, particularly the girls, had an increased rating of maladjustment (including overreactions and underreactions). CONCLUSION: Abnormalities of social adjustment are detectable in childhood in some people who develop psychotic illness. Sex and the rate of development of different components of the capacity for social interaction are important determinants of the risk of psychosis and other psychiatric disorders in adulthood.

Adult↗
PubMed1994

Search for a schizophrenia susceptibility locus on human chromosome 22.

We used 10 highly informative DNA polymorphic markers and genetic linkage analysis to examine whether a gene locus predisposing to schizophrenia is located on chromosome 22, in 105 families with schizophrenia and schizoaffective disorder. The LOD score method, including analysis for heterogeneity, provided no conclusive evidence of linkage under a dominant, recessive, or penetrance free model of inheritance. Affected sib-pair analysis was inconclusive. Affected pedigree member analysis gave only suggestive evidence for linkage. Multipoint APM analysis, using 4 adjacent loci including D22S281 and IL2RB, a region of interest from the APM analysis, gave non-significant results for the three different weighting functions.

Chromosome Mapping↗
PubMed1994

Reduced concentrations of the alpha-subunit of GTP-binding protein Go in schizophrenic brain.

Concentrations of the alpha-subunits of GTP-binding protein, Go (Go alpha) and of Gi2 (Gi2 alpha) in 6 areas (the hippocampus, parahippocampus, putamen, caudate head, orbital frontal cortex, and lateral temporal cortex) of control and schizophrenic postmortem brains were investigated using the highly sensitive enzyme immunoassay method. There was a significant decrease in Go alpha in the hippocampus and caudate head of the right hemisphere in schizophrenic patients compared to controls; the ANOVA (a general linear model; SAS Type II) demonstrated a significant diagnosis x side interaction only in the hippocampus. In other areas of the brain, analysis by grouping under diagnosis, side, age, gender, and postmortem delay showed no significant deviations in Go alpha between controls and schizophrenics. The concentrations of Gi2 alpha did not differ significantly in any area. These findings contrasted with the results yielded by ADP-ribosylation, which showed decreased pertussis toxin ADP-ribosylated amounts in the hippocampus and putamen of the contralateral (left) hemisphere. Some abnormal receptor-Go or Gi 1 signalling in hippocampus, putamen or caudate head may be involved in the pathogenesis of schizophrenia.

Aged↗
PubMed1994

Induction of beta (A4)-amyloid in primates by injection of Alzheimer's disease brain homogenate. Comparison with transmission of spongiform encephalopathy.

Amyloid plaques, associated with argyrophilic dystrophic neurites, and cerebral amyloid angiopathy (CAA), but no neurofibrillary tangles, were found in the brains of three middle-aged marmoset monkeys that had been injected intracerebrally (ic) 6-7 yr earlier with brain tissue from a patient with early-onset Alzheimer's disease. Such changes were not found in the brains of three age-matched control marmosets. Immunochemically the amyloid plaques and CAA stained with antibody to beta (A4)-protein. The plaques and CAA displayed dichroic birefringence when stained with Congo red and viewed under polarized light. beta (A4)-amyloid plaques and CAA were also found in the brain of one of two marmosets injected ic 6 yr previously with brain tissue from a patient with prion disease with concomitant beta (A4)-amyloid plaques and CAA. An occasional beta (A4)-amyloid plaque was found in the brains of two of four marmosets injected ic > 4.5 yr previously with brain tissue from three elderly patients, two of whom had suspected (but untransmitted) CJD. No beta (A4)-amyloid plaques or CAA were found in six marmosets who were older than the injected animals, in four marmosets that had not developed spongiform encephalopathy (SE) having been injected several years previously with human brain tissue from three younger patients with suspected or atypical prion disease, or in 10 younger marmosets who had undergone various neurosurgical procedures. Seventeen marmosets injected in the same way with brain tissue from patients or animals with SE developed SE 17-49 mo after injection. These results suggest that beta (A4)-amyloidosis is a transmissible process comparable to the transmissibility of SE.

Adult↗
PubMed1994

Schizophrenia and sex chromosome anomalies.

An apparent excess of sex chromosome aneuploidies (XXY, XXX, and possibly XYY) has been reported in populations of patients with schizophrenia by a number of authors. These reports have received little attention because transmission of psychosis is regarded as autosomal and not sex linked, and the detection of extra X chromosomes by Barr body estimation alone is not a reliable procedure. In this article, we review studies in which either complete karyotypes were determined for the whole sample or in which the presence of a Barr body in an individual was checked by full cytogenetic analysis. We also add two studies (of the former type) of our own--on a Swedish hospital cohort and a United States multiplex-schizophrenia family sample. These data, taken together, suggest that the sex chromosome aneuploidies, XXX and XXY, are increased in population of patients with schizophrenia, whereas too few subjects have been surveyed to determine whether an association also exists with XYY. Nevertheless, we conclude that this is consistent with a gene on the sex chromosomes having influence on the development of schizophrenia. A sex chromosome locus is compatible with an autosomal pattern of transmission if the gene is either pseudoautosomal (i.e., within the exchange region) or X-Y homologous (i.e., present in similar form in the nonrecombining regions of both X and Y chromosomes).

Adult↗
PubMed1994

Study of the Huntington's disease (HD) gene CAG repeats in schizophrenic patients shows overlap of the normal and HD affected ranges but absence of correlation with schizophrenia.

The CAG repeats in the Huntington's disease gene were investigated in chromosomes from 71 unrelated schizophrenic persons and 18 patients with schizoaffective disorder in order to determine if any of these patients had abnormal expansions. All of the probands had repeat sizes in the normal range (< 35 repeats) and there was no significant difference between the allele distributions of these patients and the normal controls. The families of two patients with 32 repeats and one patient with 34 repeats were investigated further and showed no uniform segregation of the disease with the large repeat alleles. The proband with 34 repeats inherited a chromosome that originally had 36 repeats in her father. The presence of 36 CAG repeats in members of her family and in HD patients suggests that there is an overlap between the normal and Huntington's disease CAG repeat size ranges. The more recently described CCG polymorphism in this gene was also examined in the schizophrenic and schizoaffective persons. All patients had alleles in the normal range.

Alleles↗
PubMed1994

Clinical correlates of postmortem brain changes in schizophrenia: decreased brain weight and length correlate with indices of early impairment.

From a postmortem study of the brains of 56 patients with schizophrenia and 56 controls, 38 cases whose clinical state had been objectively documented in life were examined to determine whether relations existed between features of the illness and postmortem findings. Decreased brain weight was significantly related (p < 0.05) to poor premorbid global function and to poor academic record, and decreased brain length was related to poorer premorbid global function (p < 0.05) and more severe negative symptoms. These relations are consistent with the view that morphological changes in the brain occur early in the course of the disease--that is, they are in some sense "developmental." An excess of "focal damage" in the patient group relative to controls was unrelated to the presence of morphological change or to features of illness, but was more common in female schizophrenic patients and was also correlated with evidence of cerebrovascular disease. This may possibly be due to a discrepancy between the groups in mode and cause of death.

Brain↗
PubMed1994

Etiopathogenesis and treatment of psychosis.

Psychotic illnesses (schizophrenia and schizoaffective and affective psychosis) have a lifetime prevalence of 2-3% and probably occur at a similar rate in all human societies. No etiologically significant environmental precipitants have been identified, and this suggests that these diseases are primarily genetic. Brain studies reveal that in schizophrenic patients, development of cerebral asymmetry is arrested, which may be associated with a small reduction in cortical mass. Episodes of illness can be ameliorated by dopamine (in particular D2) antagonists, drugs that are antipsychotic rather than merely antischizophrenic. The discovery of at least five dopamine receptor subtypes and their genes paves the way for new approaches to treatment. However, whether psychotic patients undergo a primary disturbance of dopaminergic transmission remains unclear.

Adult↗
PubMed1994

An examination of linkage of schizophrenia and schizoaffective disorder to the pseudoautosomal region (Xp22.3)

We investigated linkage between schizophrenia and the loci DXYS14, DXYS17, and MIC2 within the pseudoautosomal region in 85 families with two or more siblings suffering from schizophrenia or schizoaffective disorder. A maximum lod score of 2.44 was reached at MIC2, with a dominant model of inheritance at a recombination fraction of 0.367 in females and 0.046 in males (a F:M sex ratio > 1, i.e. opposite to that expected with a pseudoautosomal locus). Evidence consistent with linkage (P = 0.01) was also obtained with a sibling pair analysis at the MIC2 locus. These data do not support (although they do not definitively exclude) a locus within the pseudoautosomal region; they are consistent with the presence of a gene that predisposes to schizophrenia in the sex-specific regions of the X and Y chromosomes.

Adult↗