Quantitative Measures of Craniofacial Dysmorphology in a Family Study of Schizophrenia and Bipolar Illness.

Several laboratories, including ours, have reported an overrepresentation of craniofacial (CF) anomalies in schizophrenia (SZ). How might this dysmorphology arise in a brain-based disorder? Because the brain and face derive from shared embryologic primordia and morphogenetic forces, maldevelopmental processes may result in both CF and brain dysmorphology.Our approach is 2-pronged.

The Genetic Basis of Thought Disorder and Language and Communication Disturbances in Schizophrenia.

Thought disorder as well as language and communication disturbances are associated with schizophrenia and are over-represented in clinically unaffected relatives of schizophrenics. All three kinds of dysfunction involve some element of deviant verbalizations, most notably, semantic anomalies. Of particular importance, thought disorder characterized primarily by deviant verbalizations has a higher recurrence in relatives of schizophrenic patients than schizophrenia itself.

The power of linkage analysis of a disease-related endophenotype using asymmetrically ascertained sib pairs.

A linkage study of a qualitative disease endophenotype in a sample of sib pairs, consisting of one disease affected proband and one sibling is considered. The linkage statistic compares marker allele sharing with the proband in siblings with an abnormal endophenotype to siblings with the normal endophenotype. Expressions for the distribution of this linkage statistic, in terms of the recombination fraction are derived and (1) the genetic parameter values (allele frequency and endophenotype and disease penetrance) and (2) the abnormal endophenotype rates in the population and in classes of relatives of disease affected probands.

Model averaging in linkage analysis.

Methods for genetic linkage analysis are traditionally divided into "model-dependent" and "model-independent," but there may be a useful place for an intermediate class, in which a broad range of possible models is considered as a parametric family. It is possible to average over model space with an empirical Bayes prior that weights models according to their goodness of fit to epidemiologic data, such as the frequency of the disease in the population and in first-degree relatives (and correlations with other traits in the pleiotropic case). For averaging over high-dimensional spaces, Markov chain Monte Carlo (MCMC) has great appeal, but it has a near-fatal flaw: it is not possible, in most cases, to provide rigorous sufficient conditions to permit the user safely to conclude that the chain has converged.

Antisaccade performance in biological relatives of schizophrenia patients: a meta-analysis.

Poor performance on the antisaccade (AS) task has been interpreted as a potential indicator of genetic liability that may enhance the power of linkage studies of a multidimensional phenotype for schizophrenia. Every study has replicated the finding of significantly worse performance in schizophrenia patients regardless of which specific antisaccade paradigm was employed. In some studies involving a standard version of the antisaccade task, relatives of schizophrenia patients made an increased number of errors, but in other studies that used this same paradigm, relatives of schizophrenia patients did not differ from controls.

Linkage of eye movement dysfunction to chromosome 6p in schizophrenia: additional evidence.

Establishing the genetics of physiological traits associated with schizophrenia may be an important first step in building a neurobiological bridge between the disease phenotype and its genetic underpinnings. One of the best known of the traits associated with schizophrenia is a disorder of smooth pursuit eye tracking (ETD), which is present in 50-80% of schizophrenia patients. ETD is more than three times more prevalent in the families of a schizophrenia patient than is schizophrenia itself.

Effects of typical, atypical, and no antipsychotic drugs on visual contrast detection in schizophrenia.

Objective: Visual contrast detection has been reported in some studies to be normal in schizophrenia patients, but in other studies impairments have been reported. Because contrast detection in the visual processing system is mediated by dopamine, and because the pharmacotherapy of schizophrenia involves blocking dopamine postsynaptic receptor sites, the authors investigated the effects of dopamine-blocking antipsychotic drugs on visual contrast detection in schizophrenia.

Method: Visual contrast detection thresholds were measured in healthy subjects and schizophrenia patients receiving typical and atypical antipsychotic drugs; a two-alternative, forced-choice psychophysical method was used.

Antisaccade performance is abnormal in schizophrenia patients but not in their biological relatives.

Numerous studies have replicated the finding that schizophrenia patients make an increased number of errors on an antisaccade task. Some studies have reported that relatives of schizophrenia patients also make an increased number of antisaccade errors, a finding that has been interpreted to support the usefulness of compromised antisaccade performance as an index of genetic liability for schizophrenia. We examined performance on an antisaccade task in schizophrenia patients, nonpsychiatric controls, first-degree relatives of schizophrenia patients and first-degree relatives of nonpsychiatric controls.

Spatial and object working memory impairments in schizophrenia patients: a Bayesian item-response theory analysis.

This study reports evidence that schizophrenia patients are significantly impaired in both spatial and object (shape) working memory. A 3-s delay between exposure and recall of targets was used and Bayesian item-response theory was applied to compensate for the tasks' differential difficulty while simultaneously taking account of missing data from participant attrition. Weaker evidence was found that in schizophrenia both domains are equally impaired on average, that spatial and object working memory appear to be more highly correlated with each other in the schizophrenia population than in the normal population, and that schizophrenia patients show greater variability in spatial than object working memory performance.

Permutation tests for detecting and estimating mixtures in task performance within groups.

We propose a two-sample permutation test incorporating mixture models as a general tool for detecting and quantifying effects on task performance. We illustrate the proposed method with examples where the dependent measures under investigation are recorded for normal controls and relatives of patients with schizophrenia on a delayed response, spatial and object working memory task. Our mixture modelling in relatives allows the component distributions to arise from different continuous parametric families.