Risk of adult schizophrenia and its relationship to childhood IQ in the 1958 British birth cohort.

BACKGROUND: An inverse relationship between risk of schizophrenia and premorbid IQ is a robust empirical finding. Cognitive impairment may be a core feature of schizophrenia in addition to the clinical symptoms that have historically defined the disorder. AIMS: To evaluate whether risk of schizophrenia increases linearly or nonlinearly with the lowering of premorbid IQ after adjustment for a range of confounding factors. METHODS: IQ data from the 1958 National Child Development Study, a prospective national birth cohort (n = 17 419), were linked with psychiatric admissions in England and Wales over a 20-year period. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnoses were derived from case notes. RESULTS: A clear nonlinear inverse relationship between general intelligence at ages 7 and 11 and risk of adult psychosis was found even after adjustment for potential social, behavioral, or demographic confounding factors. No such relationship was found for affective disorders. CONCLUSIONS: The nonlinear relationship suggests an excess risk of schizophrenia in children with premorbid IQ in the learning disabilities range. Previous reports of a linear relationship are likely to be a result of less sensitive statistical methods for detecting nonlinearity.

Head movements during conversational speech in patients with schizophrenia.

BACKGROUND: Motor abnormalities are frequently described in schizophrenia, and work by Altorfer and colleagues suggests that measuring head movements during conversational speech shows differences at the level of the individual. We wished to see whether their findings, conducted using computer analysis of video obtained in motion capture suites, could be replicated using compact, portable movement sensors, in a case-control study comparing the mean amplitude of head movements during general conversation. METHODS: A referred sample of inpatients and outpatients with a diagnosis of paranoid schizophrenia was identified from case note information. Movement sensors, mounted in a baseball cap worn by subjects, transmitted data via Bluetooth to a laptop, which simultaneously captured audio to identify who was speaking. Subjects also completed a series of rating scales. RESULTS: Data from the final 11 cases and 11 controls demonstrated a substantial group difference in mean amplitude of head movement velocity during speech (p < 0.0001), although this was not significant at the level of the individual. CONCLUSIONS: Movement sensors proved well suited to capturing head movements, demonstrating a large effect size in subjects with schizophrenia.

Disentangling the relationship between hemispheric asymmetry and cognitive performance.

It is widely believed that advantages of hemispheric asymmetries originated in better cognitive processing, hence it is often implied that the relationship between hemispheric asymmetry and cognitive performance is linearly positive: the higher the degree of lateralization in a specific cognitive domain, the better the performance in a corresponding task. Yet, the empirical evidence for this notion is mixed and the statistical methods to analyze this relationship have been criticized. The present study therefore investigated the relationship between hemispheric asymmetries and cognitive performance in two behavioral tasks (a left-lateralized word-matching task and a right-lateralized face-decision task) in 230 participants (140 women, 90 men) by using two different approaches. Both methods correspondingly revealed that a relationship between hemispheric asymmetries and cognitive performance does exist. Contrary to a positive (linear) relationship however, the data could be best described by an inverted U-shaped curve. Although the optimal degree of lateralization seemed to be task-specific, a slight or moderate degree of hemispheric asymmetry achieved best cognitive performance in all tasks. Moreover, performances deteriorated towards extreme ends of lateralization (i.e., participants with either extreme left or right hemispheric biases). Taken together, the present study provides evidence against the notion that higher lateralization is related to enhanced cognitive performance.

Surface shape analysis with an application to brain surface asymmetry in schizophrenia.

Some methods for the statistical analysis of surface shapes and asymmetry are introduced. We focus on a case study where magnetic resonance images of the brain are available from groups of 30 schizophrenia patients and 38 controls, and we investigate large-scale brain surface shape differences. Key aspects of shape analysis are to remove nuisance transformations by registration and to identify which parts of one object correspond with the parts of another object. We introduce maximum likelihood and Bayesian methods for registering brain images and providing large-scale correspondences of the brain surfaces. Brain surface size-and-shape analysis is considered using random field theory, and also dimension reduction is carried out using principal and independent components analysis. Some small but significant differences are observed between the the patient and control groups. We then investigate a particular type of asymmetry called torque. Differences in asymmetry are observed between the control and patient groups, which add strength to other observations in the literature. Further investigations of the midline plane location in the 2 groups and the fitting of nonplanar curved midlines are also considered.

The effect of handedness on academic ability: a multivariate linear mixed model approach.

In recent years questions have arisen about whether there are any links between handedness and academic abilities as well as other factors. In this study we investigate the effects of gender, writing hand, relative hand skill, and UK region on mathematics and reading test scores by applying a multivariate linear mixed-effects model. A data sample based on 11,847 11-year-old pupils across the UK from the National Child Development Study was considered for the analysis. Our results show that pupils who write with one hand while having better skill with their other hand (i.e., inconsistent writing hand and superior hand) obtained lower test scores in both reading and mathematics than pupils with consistent writing hand and superior hand. Furthermore, we confirm previous findings that degree of relative hand skill has a significant effect on both reading and maths scores and that this association is not linear. We also found higher scores of reading in children from the south of England, and of mathematics in children from the south of England and Scotland, when compared to other UK regions.

Handedness in Great Britain.

Two large British databases of handedness assessed by writing hand at 10-11 years of age were analysed by geographical region. Left-handedness was found to vary significantly across regions according to one survey but not the other. In both data sets, left-handed writing was significantly more frequent in England than in Scotland and Wales combined. Possible reasons for this difference are discussed.

The structure of psychosis revisited: the role of mood symptoms.

The heterogeneity of the schizophrenia phenotype is often considered an obstacle for genetic research. We therefore aim to identify subgroups of psychosis patients with a shared symptom profile by means of a fully data-driven analysis, which may serve as an alternative phenotype. We investigated the symptoms of 1056 patients that were referred to our hospital with a psychosis. The lifetime symptoms scores were derived from the current and lifetime ratings of the comprehensive assessment of psychiatric history (CASH) interview. We used latent class analysis (LCA) to identify clusters of patients with a shared symptom profile. The five indicators in our analysis were the total number of symptoms present for each of the five factors identified in a factor analysis of lifetime symptoms. We also analysed the discriminating power of these symptom dimensions in previous LCAs. A six-cluster division of psychotic phenotypes showed substantial overlap with earlier LCA analyses and findings from genetic association studies. The results included a bipolar and a depression subgroup in psychosis and showed that mood symptoms are the best discriminators of subgroups of psychosis. The distinction of subgroups of psychosis patients, in particular those with major mood symptoms could facilitate the unravelling of the genetics of psychotic disorders.

Negative association between a history of obstetric complications and the number of neurological soft signs in first-episode schizophrenic disorder.

We examined the relationship between a history of obstetric complications (OCs) and the number of neurological soft signs (NSS) in a group of 132 patients experiencing their first episode of psychosis. We measured NSS by means of a comprehensive standardized assessment and gained information on a selection of nine OCs from the patient's mother. Contrary to our expectations we found significantly more NSS in the group of patients without a history of OCs. This effect was independent of medication in the group of patients with a schizophrenic disorder, but not in the entire group. It is possible that the patients with a history of OCs carry fewer genes for schizophrenia (and NSS) and 'needed' the OCs to develop schizophrenia.

The 2-year stability of neurological soft signs after a first episode of non-affective psychosis.

We examined the 2-year stability of neurological soft signs (NSS) in 29 patients after a first episode of psychosis. The numbers of NSS at inclusion and at 2 years follow-up were similar, but there was a significant increase in the numbers of NSS in the sub-group of patients whose dosage of antipsychotic medication had increased over time.

Lateralization of verbal ability in pre-psychotic children.

Deficits in lateralization have been reported in handedness, language and anatomical asymmetry in schizophrenia, but the relationship between these anomalies has been unclear. Extending earlier work demonstrating that degrees of lateralization are related to verbal ability in the general population, we here investigate the relationship in children who later developed psychosis. Using data from a box-marking test and an index of receptive verbal ability in the UK National Child Development study, we constructed three-dimensional plots of verbal ability in relation to left- and right-hand skill at the age of 11 years, and compared the performance of 34 children who by age 28 had developed schizophrenia and 21 who had developed affective psychosis with 12,782 in the total population. In the total population, verbal skill is decreased in those who are close to the L=R line. Children premorbid for schizophrenia are less lateralized and their verbal skill is lower than predicted by their hand skill, with a similar trend in children premorbid for affective psychosis. Thus pre-psychotic children deviate from the general population in the trajectory of lateralization of words. The findings are consistent with the concept that in psychosis at some critical stage in development there is a failure of lateralization of the components of language.

Principal curve analysis avoids assumptions of dependence between measures of hand skill.

The relationship between laterality and performance is unclear, and using laterality indices to explore this relationship can be misleading. An alternative approach is to consider laterality as a bivariate construct. A scatterplot of measures on each side will allow the distribution of values in a population to be visualised. However, determining where mean values lie in a population is problematic. Even nonparametric regression techniques such as lowess make assumptions about one variable being independent and the other dependent. Such assumptions are arbitrary in the case of measures by side. Assumptions of dependence are avoided using principal curve analysis. The results of two nonparametric fitting techniques (lowess regression and a principal curve analysis) are compared using hand skill data on 12,782 11-year-olds from a UK national birth cohort. The lowess regression is misleading. The principal curve analysis shows that absolute right-left performance differences increase with hand skill to a maximum about the point of average hand skill, and the difference is then constant up to extremes of hand skill.

Word acquisition reflects lateralization of hand skill.

Right hand preference distinguishes Homo sapiens from our closest primate relative, the chimpanzee. Are differences in degrees of handedness associated with differences in the rate of language development? To answer this question, verbal performance is examined in relation to hand skill in a UK national birth cohort dataset. Using 3-D data plots, we show that increasing dominant-hand skill is associated with increasing verbal ability, and stronger lateralization is associated with earlier acquisition of words. Thus, right-handed bias is relevant to the lateralization of language; variation along this dimension may represent species-specific genetic or 'epigenetic' diversity.