Beyond symptom dimensions: schizophrenia risk factors for patient groups derived by latent class analysis.

INTRODUCTION: Patients grouped by latent class analysis of symptoms show some consensus between studies, and may be less etiologically heterogeneous than current diagnoses. If so, the effect size of 'neurodevelopmental' risk factors may be greater than in equivalent DSMIV diagnostic groups. METHOD: Two hundred fifty six individuals with neurodevelopmental risk factors recorded in the National Child Development Study (1958) UK birth cohort were grouped by data-driven illness subtypes, derived previously in over 1000 individuals. The effect sizes of these risks were compared between data-derived and DSMIV schizophrenia (295.x) groups. RESULTS: Compared to DSMIV schizophrenia, the data-driven subtype broadly characterized by the presence of psychotic symptoms in the absence of affective symptoms showed significantly greater effect sizes in eight out of thirteen continuously-rated risk factors: birth weight, cognition, childhood behavioural problems, and neurological softsigns including handedness. CONCLUSION: A data-driven subgroup of schizophrenia patients, characterized as lacking co-morbid depressive symptoms, is less heterogeneous with respect to neurodevelopmental etiology.

A single optimum degree of hemispheric specialisation in two tasks, in two UK national birth cohorts.

How differences between the two sides of the brain (or 'laterality') relate to level of function are important components of theories of the origin and purpose of hemispheric asymmetry, although different measures show different relationships, and this heterogeneity makes discerning any underlying relationships a difficult task. There are some exceptions, for example it has been concluded that increasing lateralization (eg of hand skill or planum temporale area) occurs at the expense of the non-dominant hemisphere. However, we have previously demonstrated this latter relationship to be an artefact: a consequence of plotting two variables against each other, that are not independent of each other [Leask, S. J., & Crow, T. J. (1997) How far does the brain lateralize? An unbiased method for determining the optimum degree of hemispheric specialisation. Neuropsychologia, 36, 1275-1282; Mazoyer, B. M., & Tzourio-Mazoyer, N. G. (2004). Title Planum temporale asymmetry and models of dominance for language: a reappraisal. Neuroreport, 15, 1057-1059]. Two approaches to discerning any underlying relationships are presented in data from over 20,000 10- and 11-year olds from the 1958 and 1970 UK national cohort studies. These demonstrate that maximal performance, both cognitive and hand function, is found in association with one particular degree of functional lateralization.

The attitudes of carers and old age psychiatrists towards the treatment of potentially fatal events in end-stage dementia.

BACKGROUND: Deciding how to treat patients with end-stage dementia developing potentially fatal events has long been contentious. Under expected new legislation the role of carers is likely to increase. Old age psychiatrists frequently have to decide between active or palliative approaches to such patients. Little is known concerning the comparative attitudes of carers and old age psychiatrists. This research examined how their attitudes differed. METHODS: A Likert scale attitudinal questionnaire was designed following a literature review and was initially distributed to a pilot group of medical students to aid in establishing reliability and validity. Subsequently it was sent to all members of the local Alzheimer's Society Branch and all the old age psychiatrists in the health region. Its validity and reliability were investigated using factor analysis and test-retest reliability. Between group comparisons were then made using the students t-test and analysis of variance. RESULTS: 148 carers and 34 clinicians responded. Factor analysis and test-retest analysis of students' responses validated six questions, which grouped into two factors, relating to active treatment and patient-centred ethics. Between group comparisons revealed significant differences between carers' and clinicians' attitudes in these areas. Clinicians favoured active treatment of potentially fatal events in end-stage dementia less than carers who more significantly valued patient-centred issues such as dying with dignity, the patient's best interests and the patient's wishes. CONCLUSIONS: Old age psychiatrists and carers significantly differed in their attitudes towards treatment of potentially fatal events in end-stage dementia and this may impact on decision-making. Considerably more clinician/carer debate and dialogue seems needed.

Adult psychosis, common childhood infections and neurological soft signs in a national birth cohort.

BACKGROUND: Neurological soft signs preceding adult-onset schizophrenia suggest a neurodevelopmental origin and could reflect physical illness in childhood. AIMS: To investigate possible associations of adult-onset psychosis with neurological soft signs and common infectious illnesses in childhood. METHOD: Using data from the UK National Child Development Study, a longitudinal general population sample, odds ratios were calculated for clinical diagnoses of common childhood viral illnesses and later adult psychotic illness, childhood epilepsy and a range of neurological soft signs. RESULTS: The number of illnesses per individual did not relate either to the number of soft signs, or to any particular adult outcome. Schizophrenia, affective psychosis and epilepsy were not associated with common childhood illness but were associated with neurological soft signs and an increased, but small, frequency of previous meningitis and tuberculosis. CONCLUSIONS: Overall the data support the notion of neurological soft signs as markers of disordered neurodevelopment in schizophrenia (but the early neurological abnormalities are not caused by infectious illness) and an association between meningitis or tuberculosis in childhood and a small proportion of cases of epilepsy, affective psychosis and schizophrenia.

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.

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.

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.