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Biomedical subjects

E F Torrey

Publications and source records attributed to E F Torrey.

At least 19 recordsLinked to original sources
PubMed1998

No evidence of expansion of CAG or GAA repeats in schizophrenia families and monozygotic twins.

Many diseases caused by trinucleotide expansion exhibit increased severity and decreased age of onset (genetic anticipation) in successive generations. Apparent evidence of genetic anticipation in schizophrenia has led to a search for trinucleotide repeat expansions. We have used several techniques, including Southern blot hybridization, repeat expansion detection (RED) and locus-specific PCR to search for expanded CAG/CTG repeats in 12 families from the United Kingdom and 11 from Iceland that are multiplex for schizophrenia and demonstrate anticipation. The unstable DNA theory could also explain discordance of phenotype for schizophrenia in pairs of monozygotic twins, where the affected twin has a greater number of repeats than the unaffected twin. We used these techniques to look for evidence of different CAG/CTG repeat size in 27 pairs of monozygotic twins who are either concordant or discordant for schizophrenia. We have found no evidence of an increase in CAG/CTG repeat size for affected members in the families, or for the affected twins in the MZ twin sample. Southern hybridization and RED analysis were also performed for the twin and family samples to look for evidence of expansion of GAA/TTC repeats. However, no evidence of expansion was found in either sample. Whilst these results suggest that these repeats are not involved in the etiology of schizophrenia, the techniques used for detecting repeat expansions have limits to their sensitivity. The involvement of other trinucleotide repeats or other expandable repeat sequences cannot be ruled out.

Base Sequence↗
PubMed1998

Olfactory function in monozygotic twins discordant for schizophrenia.

OBJECTIVE: Abnormalities of olfactory identification ability have been proposed as a marker of cerebral dysfunction in schizophrenia. The authors studied the potential role of genetic factors in olfactory dysfunction by assessing monozygotic twins discordant for schizophrenia and matched comparison subjects. METHOD: The subjects were 12 pairs of monozygotic twins discordant for schizophrenia and 12 healthy subjects matched for sex and age. Each subject completed the University of Pennsylvania Smell Identification Test. RESULTS: The combined twin group scored significantly lower on smell identification than did the comparison group. The affected and unaffected twin groups did not differ from each other. CONCLUSIONS: Genetic factors may contribute to cerebral dysfunction as assessed by olfactory identification ability.

Adult↗
PubMed1997

Multivariate analysis of RNA levels from postmortem human brains as measured by three different methods of RT-PCR. Stanley Neuropathology Consortium.

The analysis of RNA from postmortem human brain tissue by reverse transcription-polymerase chain reaction (RT-PCR) provides a practical method to measure both normal and abnormal brain gene expression. A major limitation in using human material is that yields can vary dramatically from individual to individual, making comparisons between samples difficult. In this report, we study the association of pH and several pre- and postmortem factors on the RNA yields from 89 postmortem human occipital cortices. Glyceraldehyde phosphate dehydrogenase (GAPdH) mRNA levels were measured by RT-PCR. A major variant in this method is the priming used in the reverse transcription reaction. Three different methods of reverse transcription were performed and the resultant levels of products compared against the pre- and postmortem factors and pH. The levels of GAPdH correlated significantly to pH and pH itself to the rapidity of death (RoD) (agonal state) indicating that premortem factors may play the greatest role in determining postmortem RNA levels. The three methods of priming showed different sensitivities, most notably that oligo dT priming alone is vulnerable to long freezer intervals (FI). We conclude that premortem factors are the major affectors of RNA levels variations and that the polyA tail region of the molecule appears to be adversely affected by extended freezer storage.

Autopsy↗
PubMed1997

Seasonality of births in schizophrenia and bipolar disorder: a review of the literature.

More than 250 studies, covering 29 Northern and five Southern Hemisphere countries, have been published on the birth seasonality of individuals who develop schizophrenia and/or bipolar disorder. Despite methodological problems, the studies are remarkably consistent in showing a 5-8% winter-spring excess of births for both schizophrenia and mania/bipolar disorder. This seasonal birth excess is also found in schizoaffective disorder (December-March), major depression (March-May), and autism (March) but not in other psychiatric conditions with the possible exceptions of eating disorders and antisocial personality disorder. The seasonal birth pattern also may shift over time. Attempts to correlate the seasonal birth excess with specific features of schizophrenia suggest that winter-spring births are probably related to urban births and to a negative family history. Possible correlations include lesser severity of illness and neurophysiological measures. There appears to be no correlation with gender, social class, race, measurable pregnancy and birth complications, clinical subtypes, or neurological, neuropsychological, or neuroimaging measures. Virtually no correlation studies have been done for bipolar disorder. Regarding the cause of the birth seasonality, statistical artifact and parental procreational habits are unlikely explanations. Seasonal effects of genes, subtle pregnancy and birth complications, light and internal chemistry, toxins, nutrition, temperature/weather, and infectious agents or a combination of these are all viable possibilities.

Bipolar Disorder↗
PubMed1997

Urban birth and residence as risk factors for psychoses: an analysis of 1880 data.

It is known that social drift to cities increases the urban prevalence for severe mental illnesses. Recent studies in England and Sweden have reported that being born in, or raised in, an urban area is also a risk factor for later developing schizophrenia. The present study utilized 1880 census data, the most complete enumeration of severely mentally ill individuals ever done in the United States, to examine the association of urban residence and severe mental illnesses. Individuals identified as having one of seven forms of 'insanity' (n = 91959) were allocated to their county of origin (n = 2661) in the census. Rates of 'insane' persons per 1000 population were calculated for each county. The counties were then divided by degree of urbanization based on the largest cities and the percentage of population living in towns of 4000 or more. The point prevalence of 'insanity' in the United States as a whole in 1880 was 1.8 per 1000. There was a significant association between 'insanity' by county and degree of urbanization, with odds ratios of 1.66 for urban, 1.46 for semi-urban, and 1.44 for semi-rural, and 1.37 for rural, using completely rural counties as a baseline. Most completely rural counties with high rates included mining camps, lumbering camps, or fishing villages, and not farming areas. In addition to urban drift, urban birth and residence appear to be risk factors for developing severe mental illnesses. Psychological and biological explanations have both been proposed. However, recent studies reporting winter birth and urban birth or residence as synergistic risk factors favor the latter.

Cluster Analysis↗
PubMed1997

Metabolites of the antipsychotic agent clozapine inhibit the replication of human immunodeficiency virus type 1.

Schizophrenia is a serious and often debilitating neuropsychiatric disease of worldwide importance. Current therapy relies on the use of typical antipsychotic medications, which specifically inhibit binding of ligand at the D2 dopamine receptor, and atypical medications which display little activity for this receptor interaction. While atypical antipsychotic agents have been shown to variably inhibit other neuroreceptor-ligand interactions, the exact mechanisms for the therapeutic efficacy of these medications have not been completely defined. Clozapine, an atypical antipsychotic, and nine of its metabolites were studied in vitro for possible antiviral activity against a model of a human neurotropic virus, human immunodeficiency virus type 1 (HIV-1). In an assay for inhibition of virus-induced cytopathic effect (CPE) two metabolites demonstrated antiviral activity (ID50 = 37-85 micrograms/ml) (119-289 microM), while other atypical or novel antipsychotics as well as typical medications had no effect. Based on an ELISA, four chemically similar metabolites inhibited the production of p24, the major internal antigen of HIV (ID50 = 11.6-15.7 micrograms/ml) (38-51 microM). These data suggest that the therapeutic efficacy of some antipsychotics may be due in part to an ability to inhibit viral replication. Antiviral agents may prove to be effective adjuncts in the treatment of schizophrenia.

Anti-HIV Agents↗
PubMed1997

Monozygotic twins discordant for schizophrenia are discordant for N-CAM and L1 in CSF.

While schizophrenia has a genetic component, its pathogenesis is unknown. Abnormal concentrations of two cell recognition molecules (CRMs), neural-cell adhesion molecule (N-CAM) and L1 antigen have been described in the cerebrospinal fluid (CSF) of patients with schizophrenia. Studies of monozygotic twins discordant for schizophrenia may help separate genetic and environmental contributions to the disease. In the present study of monozygotic twins discordant for schizophrenia, the affected twins had increased N-CAM and decreased L1 antigen in their CSF. Non-affected twins were not different from normals. Although processes related to genetic instability cannot be entirely ruled out, these results suggest that these abnormalities are not a part of the genetic predisposition to become schizophrenic. Thus the changes in N-CAM and L1 antigen may reflect either the events which precipitated the onset of schizophrenia, or events which are associated with the experience of having the disease.

Analysis of Variance↗
PubMed1997

A quantitative analysis of smooth pursuit eye tracking in monozygotic twins discordant for schizophrenia.

BACKGROUND: Previous studies of discordant monozygotic (MZ) twins have suggested that abnormal smooth pursuit eye tracking is an indicator of genetic liability for schizophrenia. We attempted to replicate this in a different sample of twins. METHODS: Probands from 12 sets of MZ twins discordant for schizophrenia who met DSM-III-R criteria for schizophrenia or schizoaffective disorder and their co-twins without psychiatric diagnosis (except 2 with a history of substance abuse) and 12 sets of normal control MZ twins. Psychiatric diagnosis was based on Structured Clinical Interview; monozygosity was based on analysis of 19 red blood cell antigens. Smooth pursuit eye movement gain (equal to the ratio of eye-target velocity) and numbers, amplitudes, and subtypes of saccadic eye movements were compared. Measures were derived from computer analysis of digitized infrared oculographic recordings of constant velocity (16.67 degrees per second) smooth pursuit eye tracking. RESULTS: Quantitative measures of eye tracking for the affected twin were inferior to those of the unaffected co-twin, with affected twins showing significant decreases in gain and significant increases in numbers and amplitudes of total and intrusive saccades. Moreover, whereas means for the group of affected twins differed significantly from those of normal controls on measures of gain and total saccades, means for the group of unaffected co-twins were well within the normal range. CONCLUSIONS: These data are consistent with the hypothesis that abnormal eye tracking is associated with the expression of illness, or phenotype, in schizophrenia, at least in this twin sample. The data raise questions regarding the use of eye tracking measurement for identifying putative gene carriers among at-risk relatives in genetic linkage studies of schizophrenia.

Adolescent↗
PubMed1996

Cortical gyral anatomy and gross brain dimensions in monozygotic twins discordant for schizophrenia.

BACKGROUND: This study combines recent advances in three-dimensional neuroimaging technology and the genetic constraints inherent in monozygotic (MZ) twins to examine surface gyral anatomy and gross brain dimensions in monozygotic twin pairs discordant for schizophrenia. Results are presented and evaluated with respect to prior observations of cortical anomalies in schizophrenia and the hypothesis that schizophrenia involves cortical maldevelopment. DESIGN: Three-dimensional renderings from volumetric magnetic resonance imaging (MRI) data of 13 MZ twin pairs discordant for schizophrenia and nine normal MZ pairs were studied. Qualitative assessments of left and right hemisphere surfaces were made by raters blind to diagnosis in an effect to identify developmental gyral abnormalities such as vertical temporal gyri or microgyria. Measurement of brain hemisphere length, area, and volume were also determined. These data were compared within discordant MZ schizophrenia pairs, within normal MZ pairs, and between matched unaffected discordant and normal MZ groups. RESULTS: Raters did not identify qualitatively abnormal gyri in the schizophrenia subjects to enable distinction from their unaffected co-twins or from normal controls. Brain hemisphere volumes in the affected DS were significantly smaller bilaterally by about 3% compared with their unaffected DS co-twins, who did not differ from normals on this measure. CONCLUSIONS: We were unable to confirm previous reports of vertical gyri or localized gyral thinning as being characteristic of the cortical anatomy of schizophrenia. If cortical maldevelopment is associated with schizophrenia it does not appear to disrupt gross gyral pattern formation in these ways. The quantitative results of diminished hemisphere volume and length in the twins with schizophrenia are consistent with previous reports of smaller brain size in schizophrenia. Our results suggest that this is a bilateral phenomenon that may be dependent, at least in part, on environmental factors.

Adult↗
PubMed1996

Birth seasonality in bipolar disorder, schizophrenia, schizoaffective disorder and stillbirths.

BACKGROUND: More than 40 studies have been done on seasonal birth patterns for schizophrenia, but only two small studies have been done for DSM-III-R bipolar disorder and none for schizoaffective disorder. Two studies have also reported a significant relationship between schizophrenia births and stillbirths. METHODS: In the largest study to date, birth data from four states was obtained on 126,987 state psychiatric hospitals inpatients divided into 'process' schizophrenia (disorganized, catatonic, undifferentiated), paranoid schizophrenia, schizoaffective disorder, bipolar disorder and major depression. Time series analysis compared these births to all general births and to stillbirths. RESULTS: 'Process' schizophrenia, paranoid schizophrenia, schizoaffective disorder and bipolar disorder all had statistically significant seasonal excess births from December through March (p = 0.0000). The largest excess was 5.8% for bipolar disorder. Major depression had significant excess births from March through May. Time series analysis showed statistically significant coherences between major depression and bipolar disorder (0.995) and between schizoaffective disorder and both 'process' schizophrenia (0.977) and bipolar disorder (0.977). Unexpectedly, a significant coherence was also found between paranoid schizophrenia and bipolar disorder (0.972). Excess stillbirths were found for each month from January through June and a significant coherence was found between stillbirths and paranoid schizophrenia (0.998). CONCLUSIONS: This study demonstrates that DSM-III-R bipolar disorder and schizoaffective disorder both have an excess of winter births, similar to that found in schizophrenia. Time series analysis, however, suggests that the causes may not be identical. Major depression, by contrast, has an excess of spring births.

Bipolar Disorder↗
PubMed1996

Plasma protein variations in monozygotic twins discordant for schizophrenia.

Monozygotic twins discordant for schizophrenia were analyzed by two-dimensional (2-D) gel electrophoresis to identify extrahereditary factors important in the development of schizophrenia. Plasma protein patterns in 2-D gels of monozygotic twins discordant for schizophrenia were found to be significantly less alike than those of normal control monozygotic twins. Several polypeptide spots were found to be elevated in the plasma of the schizophrenic twin. One of these polypeptides, spot 782, was also found to be significantly (p < .001) elevated when schizophrenic patients were compared to unrelated normal control individuals. Spot 782 may be an isoform of haptoglobin. Quantitative variations in some plasma haptoglobin levels were seen between discordant twins, but not between unrelated schizophrenic and normal control individuals.

Adult↗
PubMed1996

Search for viral nucleic acid sequences in brain tissues of patients with schizophrenia using nested polymerase chain reaction.

BACKGROUND: We used polymerase chain reaction to search for nucleic acid sequences of several viruses in DNA and RNA extracted from brain tissues of schizophrenic and control subjects. METHODS: We extracted DNA and RNA templates from frozen brain specimens of 31 patients with schizophrenia and 23 nonschizophrenic control patients with other diseases. The extracts were subjected to polymerase chain reaction with oligonucleotide primers for 12 different viruses (cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1, human herpesvirus type 6, varicellazoster virus, measles virus, mumps virus, rubella virus, the picornavirus group, influenza A virus, human T-cell lymphotropic virus type I, and St Louis encephalitis virus), several of which have been suspected of involvement in schizophrenia. Nested primers were used to increase the sensitivity of the method. RESULTS: No amplified nucleic acid sequences encoded by the selected viral genomes were detected in extracts of any brain specimens from either schizophrenic or control patients. CONCLUSIONS: These data agree with previous studies that failed to find sequences of a number of viruses in the cerebrospinal fluid or selected areas of the brains of schizophrenic patients. Additional efforts should be undertaken to identify other known and unknown pathogens in schizophrenia, sampling more areas of the brain from subjects with a variety of clinical types of schizophrenia.

Brain↗