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Biomedical subjects

L E DeLisi

Publications and source records attributed to L E DeLisi.

At least 55 records · Page 3Linked to original sources
PubMed1996

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. Neither two-point nor multipoint non-parametric analyses reached significance at a level less than 0.01 for any markers examined in the region and lod score analyses were not suggestive of linkage. Based on initial findings in the present data set and recently published linkage results, two specific areas were densely covered with markers and tested for linkage disequilibrium. After correcting for multiple comparisons within each locus, no significant deviation from expected allele transmission ratios was observed. The present findings together with the published literature fail to find consistent evidence of a linkage for schizophrenia to a single locus on chromosome 6.

Adult↗
PubMed1996

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. The present report addresses some of these problems and examines the hypothesis that schizophrenia may be associated with an alteration in normal patterns of functional laterality. In addition, the relationship between patterns of laterality and cognitive functioning was assessed. Twenty-one schizophrenic patients and 24 control subjects, all right-handed, were compared on two neuropsychological batteries, one designed to test cerebral dominance and the other, cognitive performance. Cerebral dominance was measured by two dichotic listening tests (verbal and nonverbal) and three motoric tests. Cognitive ability was assessed with a comprehensive neuropsychological battery. Schizophrenic and control subjects differed significantly in performance on laterality measures, but they did not differ in patterns of functional laterality when performance was taken into account. In addition, it was shown that the relationship between cognitive ability and laterality is complex, with some aspects of laterality appearing to be beneficial to cognitive ability.

Adult↗
PubMed1996

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. We and others believe that the TATA-binding protein (TBP) is an important candidate to investigate in these diseases as it contains a highly polymorphic stretch of glutamine codons, which are close to the threshold length where the polyglutamine tracts start to be associated with disease. Thus, we examined the lengths of this polyglutamine repeat in normal unrelated East Anglians, South African Blacks, sub-Saharan Africans mainly from Nigeria, and Asian Indians. We also examined 43 bipolar affective disorder patients and 65 schizophrenic patients. The range of polyglutamine tractlengths that we found in humans was from 26-42 codons. No patients with bipolar affective disorder and schizophrenia had abnormal expansions at this locus.

Africa↗
PubMed1996

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. Many additional genes with trinucleotide repeats are believed to be expressed in the human brain. As anticipation has been reported in schizophrenia and bipolar affective disorder, we have examined allele distributions of 13 trinucleotide repeat-containing genes, many novel and all expressed in the brain, in genomic DNA from schizophrenic (n = 20-97) and bipolar affective disorder patients (23-30) and controls (n = 43-146). No evidence was obtained to implicate expanded alleles in these 13 genes as causal factors in these diseases.

Base Sequence↗
PubMed1996

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. The 2743 bp cDNA contains a 1077 bp open reading frame encoding 359 amino acids. This amino acid sequence is homologous (56% amino acid identify and 81% amino acid conservation) to the Caenorhabditis elegans cell fate-determining protein mab-21. CAGR1 is expressed in several human tissues, most prominently in the cerebellum, as a message of approximately 3.0 kb. The gene was mapped to 13q13, just telomeric to D13S220. A 5'-untranslated CAG trinucleotide repeat is highly polymorphic, with repeat length ranging from six to 31 triplets and a heterozygosity of 87-88% in 684 chromosomes from several human populations. One allele from an individual with an atypical movement disorder and bipolar affective disorder type II contains 46 triplets, 15 triplets longer than any other allele detected. Though insufficient data are available to link the long repeat to this clinical phenotype, an expansion mutation of the CAGR1 repeat can be considered a candidate for the etiology of disorders with anticipation or developmental abnormalities, and particularly any such disorders linked to chromosome 13.

Amino Acid Sequence↗
PubMed1996

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. RESULTS: A significant cortical gray matter deficit and lateral ventricular enlargement were found in schizophrenic patients relative to the comparison group. CONCLUSIONS: The presence of the cortical gray matter deficit close to onset of illness supports the role of preexisting structural brain deficits in the genesis of schizophrenia.

Adult↗
PubMed1995

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.

Chromosome Mapping↗
PubMed1995

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. Total volume reduction was noted in both hemispheres to a greater degree in patients than controls. When adjusted for total brain size, left ventricular enlargement occurred in patients, but not controls, over time. These preliminary data suggest that subtle cortical atrophy may be occurring over time after the onset of illness.

Adult↗
PubMed1995

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. When unipolar, it more often is expressed in female than male relatives (particularly mothers), and when bipolar it is more likely in males. In contrast, schizophrenia with and without depression is equally prevalent in both sexes. Unipolar illness was more common in relatives of schizophrenics whose illnesses are characterized by recurrent episodes of depression than in those whose are not. These data are consistent with the hypothesis that the same genes could contribute to susceptibility to both schizophrenia and affective disorder in some families, and that sex and phenotypic expression are in some way related. However, the phenomenon of high rates of depression in mothers of schizophrenic patients needs explanation.

Adult↗
PubMed1994

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. Small positive lod scores were obtained for loci pericentromeric, from Xp11.4 to Xq12. Lod scores were also computed separately in families selected for evidence of maternal inheritance and absence of male to male transmission of psychosis. The lod score for linkage to the locus DXS7 reached a maximum of 1.83 at 0.08% recombination, assuming dominant inheritance on the X chromosome in these families (n = 34). Further investigation of the X-Y homologous gene hypothesis focussing on this region is warranted.

Chromosome Mapping↗
PubMed1994

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. The results of this study suggest that women who are first-episode schizophrenic patients have a smaller total corpus callosum area than female controls, with no difference noted for men. In normal controls, a larger corpus callosum was associated with better cognitive function, whereas in schizophrenics, no such relationship emerged.

Adult↗
PubMed1994

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.e. dyslexia. Since disordered language is one of the hallmarks of schizophrenia, the present study focuses on the planum temporale and related superior temporal gyrus. Eighty-five first-episode schizophrenic patients and 40 controls had measurements of the sylvian fissure taken from coronal slices. The pattern of asymmetry in controls was for the right length to be longer than the left in anterior slices, and for left to be longer than right in posterior slices (corresponding to the planum temporale). Schizophrenic patients as a group demonstrated less asymmetry (R > L) in anterior slices, and female patients showed a trend for less (L > R) asymmetry in posterior slices. In contrast to the report of Barta et al. (1990), the volume of the anterior superior temporal gyrus did not differ from controls in first-episode schizophrenic patients. Neither the presence of formal thought disorder nor auditory hallucinations defined a subgroup of patients with reduced size or lateralization of the planum temporal or superior temporal gyrus.

Adult↗
PubMed1994

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. We also add two studies (of the former type) of our own--on a Swedish hospital cohort and a United States multiplex-schizophrenia family sample. These data, taken together, suggest that the sex chromosome aneuploidies, XXX and XXY, are increased in population of patients with schizophrenia, whereas too few subjects have been surveyed to determine whether an association also exists with XYY. Nevertheless, we conclude that this is consistent with a gene on the sex chromosomes having influence on the development of schizophrenia. A sex chromosome locus is compatible with an autosomal pattern of transmission if the gene is either pseudoautosomal (i.e., within the exchange region) or X-Y homologous (i.e., present in similar form in the nonrecombining regions of both X and Y chromosomes).

Adult↗
PubMed1994

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. The proband with 34 repeats inherited a chromosome that originally had 36 repeats in her father. The presence of 36 CAG repeats in members of her family and in HD patients suggests that there is an overlap between the normal and Huntington's disease CAG repeat size ranges. The more recently described CCG polymorphism in this gene was also examined in the schizophrenic and schizoaffective persons. All patients had alleles in the normal range.

Alleles↗
PubMed1993

DSM-III-R personality disorders in parents of schizophrenic patients.

This study examines the frequency of DSM-III-R personality disorders in parents of 58 patients who were admitted consecutively to a New York State psychiatric hospital with a first admission for a schizophrenia-like psychosis. For comparison, a control group of 65 families were randomly recruited who were in the same age group and denied any psychiatric history in their immediate families. Significantly more parents of the patients had a diagnosed personality disorder than controls. These were classified as schizoid, schizotypal, histrionic, and sadistic types by DSM-III-R criteria. While paranoid personality disorder was frequent, it was equally distributed among both groups of parents. These data suggest that the genetic boundaries to a "schizophrenia spectrum" disorder may extend further than previously thought and particularly the specific characteristics that are common to a wide variety of these disorders need to be examined in further analyses.

Case-Control Studies↗