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.