Cortical gray matter volume deficit in patients with first-episode schizophrenia.

Objective: A cortical gray matter deficit has been found in cross-sectional studies of patients with chronic schizophrenia. The purpose of this study was to examine whether this deficit is present early in the course of illness.

Method: The authors measured cortical gray matter volume on magnetic resonance images acquired within 6 months of onset of illness from 22 patients with first-episode schizophrenia and 51 age-matched comparison subjects from the Stony Brook First Episode Study.

Linkage analyses of schizophrenia to chromosome 6p24-p22: an attempt to replicate.

The present study evaluates evidence for linkage of schizophrenia to chromosome 6p24-p22. An independent sample of 211 families ascertained on the basis of having an affected sib-pair diagnosed with schizophrenia or schizoaffective disorder was assessed with seventeen polymorphic markers spanning a 37cM region. Linkage analysis was performed with parametric and non-parametric methods to test for cosegregation using 4 models of inheritance.

Chromosome 18 translocation (18;21) (p11.1;p11.1) associated with psychosis in one family.

In the course of recruiting families with 2 schizophrenic siblings for genome screening and linkage studies, a family was found with mental retardation, schizophrenia, and/or other related psychotic illnesses in individuals who also had an unbalanced or balanced translocation between chromosomes 21-18 [t(18;21)(p11.1;p11.1)].

Functional asymmetries in schizophrenia and their relationship to cognitive performance.

Previous accounts of cerebral dominance in schizophrenic patients have been conflicting. While many studies report decreased patterns of functional laterality in schizophrenic subjects, others report increases or no differences. Conceptual differences in the definition of laterality and its effects on behavior may be a reason for the poor concordance among studies.

Analysis of polyglutamine-coding repeats in the TATA-binding protein in different human populations and in patients with schizophrenia and bipolar affective disorder.

A new class of disease (including Huntington disease, Kennedy disease, and spinocerebellar ataxias types 1 and 3) results from abnormal expansions of CAG trinucleotides in the coding regions of genes. In all of these diseases the CAG repeats are thought to be translated into polyglutamine tracts. There is accumulating evidence arguing for CAG trinucleotide expansions as one of the causative disease mutations in schizophrenia and bipolar affective disorder.

cDNA cloning of a human homologue of the Caenorhabditis elegans cell fate-determining gene mab-21: expression, chromosomal localization and analysis of a highly polymorphic (CAG)n trinucleotide repeat.

The two most consistent features of the diseases caused by trinucleotide repeat expansion-neuropsychiatric symptoms and the phenomenon of genetic anticipation-may be present in forms of dementia, hereditary ataxia, Parkinsonism, bipolar affective disorder, schizophrenia and autism. To identify candidate genes for these disorders, we have screened human brain cDNA libraries for the presence of gene fragments containing polymorphic trinucleotide repeats. Here we report the cDNA cloning of CAGR1, originally detected in a retinal cDNA library.

Analysis of thirteen trinucleotide repeat loci as candidate genes for schizophrenia and bipolar affective disorder.

A group of diseases are due to abnormal expansions of trinucleotide repeats. These diseases all affect the nervous system. In addition, they manifest the phenomenon of anticipation, in which the disease tends to present at an earlier age or with greater severity in successive generations.

A combined analysis of D22S278 marker alleles in affected sib-pairs: support for a susceptibility locus for schizophrenia at chromosome 22q12. Schizophrenia Collaborative Linkage Group (Chromosome 22).

Several groups have reported weak evidence for linkage between schizophrenia and genetic markers located on chromosome 22q using the lod score method of analysis. However these findings involved different genetic markers and methods of analysis, and so were not directly comparable. To resolve this issue we have performed a combined analysis of genotypic data from the marker D22S278 in multiply affected schizophrenic families derived from 11 independent research groups worldwide.

Failure to find a chromosome 18 pericentric linkage in families with schizophrenia.

A recent report of a possible linkage of bipolar affective disorder to a pericentric region of chromosome 18 initiated the present investigation to search for a similar linkage in 32 families with schizophrenia. The results of a study using 5 markers mapped to this region show negative lod scores and only weak evidence for any linkage by nonparametric analyses. If the previously reported finding is a true positive linkage for bipolar disorder, then either it is unlikely to be related to the genetics of schizophrenia, or the proportion of families linked to this region is small.

A prospective follow-up study of brain morphology and cognition in first-episode schizophrenic patients: preliminary findings.

Brain morphological abnormalities have been reported in several independent investigations of chronic schizophrenic patients. The present study is a prospective 4-year follow-up of first-episode schizophrenic patients to determine whether some of these abnormalities may be a consequence of regional brain structural change over time after the onset of a first psychotic episode. Whole hemisphere, temporal lobes, superior temporal gyrus, hippocampus, caudate, corpus callosum, and lateral ventricles were measured in a series of MRI scans taken over a 4-year period in 20 patients and five controls.

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.

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.

Gender differences in corpus callosum size in first-episode schizophrenics.

Previous studies indicate differences between schizophrenics and normals in thickness and overall size of the corpus callosum, particularly in female subjects. The present study compares the area of the corpus callosum as measured by magnetic resonance imaging (MRI) in men and women experiencing first-episode cases of schizophrenia. The corpus callosum area is also correlated with measures of neuropsychological function.

Search for linkage to schizophrenia on the X and Y chromosomes.

Markers for X chromosome loci were used in linkage studies of a large group of small families (n = 126) with at least two schizophrenic members in one sibship. Based on the hypothesis that a gene for schizophrenia could be X-Y linked, with homologous loci on both X and Y, our analyses included all families regardless of the pattern of familial inheritance. Lod scores were computed with both standard X-linked and a novel X-Y model, and sib-pair analyses were performed for all markers examining the sharing of maternal alleles.

Asymmetries in the superior temporal lobe in male and female first-episode schizophrenic patients: measures of the planum temporale and superior temporal gyrus by MRI.

Schizophrenia has been hypothesized to be associated with an underlying brain developmental anomaly, specifically affecting normal brain asymmetries. The most pronounced asymmetries are present on the superior surface of the temporal lobes, the left plane, as measured along the sylvian fissure (planum temporale) being longer than the right in the majority of normal individuals. These asymmetries encompass Wernicke's area, the anatomical substrate for language, and have been found to be less pronounced in individuals with developmental language problems, i.

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.

Linkage analysis between schizophrenia and a microsatellite polymorphism for the D5 dopamine receptor gene.

Using 23 multiplex pedigrees we tested for linkage between schizophrenia and a microsatellite polymorphism for the D5 dopamine receptor gene (DRD5). Assuming autosomal dominant inheritance and a maximum penetrance of 0.6, an overall lod score of -4.

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.

Increased prevalence of cavum septum pellucidum in schizophrenia.

A previous report that the presence of a cavum septum pellucidum was significantly more common in schizophrenic patients than in control subjects (DeGreef et al., 1992) stimulated the present study of an independent but similar population of first admission schizophrenic patients. A high prevalence of this developmental anomaly (44.

Search for a genetic event in monozygotic twins discordant for schizophrenia.

When monozygotic twins are discordant for the diagnosis of schizophrenia, this discordance has been traditionally attributed to environmental factors acting upon a genome susceptible for the schizophrenia phenotype. The study presented here was designed to examine the occurrence of a genetic event, such as a postzygotic mitotic crossover, that could account for the discordance. Such a postzygotic event could affect cis-acting sequences and result in a phenotype of variable severity.