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E F Torrey

Publications and source records attributed to E F Torrey.

At least 91 records · Page 5Linked to original sources
PubMed1993

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. We used molecular genetic methods to evaluate such an event with 94 microsatellite repeat polymorphic markers distributed on all autosomes and the X chromosome in five pairs of monozygotic twins discordant for schizophrenia. In this search, no genetic marker discordances were identified between the co-twins. The lack of a genetic difference may implicate nongenetic factors that are responsible in eliciting or suppressing the phenotype. However, the experiments performed in this study cannot eliminate the possibility that a tissue-specific mitotic crossover might have occurred in one of the discordant twins, which could not have been detected in our current study.

Adult↗
PubMed1993

Handedness in twins with schizophrenia: was Boklage correct?

Boklage's report of increased non-right handedness among monozygotic twins with schizophrenia has been cited as evidence to support an association of abnormal brain lateralization with the development of schizophrenia. The present study found no such association. Two previous attempts to replicate Boklage's findings (Luchins et al. 1980; Lewis et al. 1989) also reported little support. Studies of twin handedness do not appear to support an association of brain lateralization and schizophrenia.

Adolescent↗
PubMed1993

Learning and memory in monozygotic twins discordant for schizophrenia.

Learning and memory were assessed in 24 monozygotic (MZ) pairs of individuals discordant for schizophrenia or delusional disorder and seven normal pairs of MZ twins. On declarative memory tasks, the affected group displayed a pattern that might best be characterized as dysmnesic in that they performed significantly worse than the discordant unaffected group on story recall, paired associated learning, and visual recall of designs, but they learned over time, had relatively preserved recognition memory, and did not show profoundly accelerated rates of forgetting. Effortful, volitional retrieval from the lexicon, measured by verbal fluency, was also compromised in the affected group. On the other hand, procedural learning of the motor skill in a pursuit rotor task was relatively intact in the affected group. Comparisons of the normal group and unaffected group indicated that the latter group had very mild impairments in some aspects of episodic memory, namely, immediate and delayed recall of stories and delayed recall of designs. It is highly unlikely that the impairments observed in the affected group can be attributed to differences in genome, family environment, socioeconomic circumstance, or educational opportunity, as all of these were controlled by the twin paradigm. Rather, the impairments appear to be related to the intercession of disease. The neuropsychological profile is consistent with frontal lobe and medial temporal lobe dysfunction, as noted in this sample as well as other samples of schizophrenic singletons. Significant correlations between many measures of memory and global level of social and vocational functioning within the discordant group were also found. Thus difficulties in rapidly acquiring new information and propitiously retrieving old information may burden patients with schizophrenia in many of the transactions of everyday life.

Adolescent↗
PubMed1993

Seasonality of schizophrenia and stillbirths.

A study of the birth pattern of 30,467 patients with schizophrenia and 428,406 stillbirths in New York State showed a significant winter-month excess in both schizophrenia births (p = 0.0000) and stillbirths (p = 0.0000). Excess births of individuals with schizophrenia in November and December provided additional evidence to refute the age-incidence explanation for the observed seasonality. Time series spectral analysis showed coherence in the pattern of schizophrenia births and stillbirths of 0.898 (p < 0.003) with schizophrenia births preceding stillbirths by 13 days. These results suggest that a common etiological seasonal factor affects a subgroup of births of individuals who later develop schizophrenia and a subgroup of stillbirths. Nutritional factors, temperature, and infectious agents known to cause both central nervous system disease and stillbirths are possible candidates.

Adult↗
PubMed1993

Quality and cost of services for seriously mentally ill individuals in British Columbia and the United States.

OBJECTIVE: To better understand the strengths and weaknesses of systems of services for seriously mentally ill individuals in Canada and the United States, the quality and cost of services in the province of British Columbia (population 3.2 million) were compared with those of services in the 50 states. METHODS: A survey of selected psychiatric facilities, data from the Canadian Ministry of Health, and information from families and consumers were assessed using methods similar to those used in a 1990 survey that rated services for individuals with serious mental illness in the 50 states. Separate scores were given for hospitals, outpatient and community support services, rehabilitation services, housing, and children's services. RESULTS: British Columbia scored higher than any single state in the United States and more than twice as high as 40 states on the quality of services for seriously mentally ill individuals. Compared with the states, British Columbia ranked ninth in cost of services per capita. When ratings of quality and cost were combined, British Columbia appeared to be delivering services almost twice as good as those in New York State at about half the cost. However, recent trends, such as shortages of inpatient beds and increasing numbers of seriously mentally ill persons among the homeless population, suggest that British Columbia's services may be deteriorating. CONCLUSIONS: Probable reasons for the superior services for seriously mentally ill individuals in British Columbia include single-source funding, a strong mandate to treat such individuals, and a comprehensive approach to providing services. The Canadian health system, as implemented in British Columbia, has definite advantages for individuals with serious mental illnesses.

Adult↗
PubMed1992

Regional cerebral blood flow in monozygotic twins discordant and concordant for schizophrenia.

We addressed several questions regarding hypofunction of the prefrontal cortex ("hypofrontality") in schizophrenia by measuring regional cerebral blood flow during three different cognitive conditions in monozygotic twins who were discordant or concordant for schizophrenia or who were both normal. These questions included the prevalence of hypofrontality, the importance of genetic predisposition, and the role of long-term neuroleptic treatment. Significant differences between affected and unaffected discordant twins were found only during a task linked to the prefrontal cortex, the Wisconsin Card Sorting Test. During this condition, all of the twins with schizophrenia were hypofrontal compared with their unaffected co-twins, suggesting that, if appropriate cognitive conditions and control groups are used, hypofrontality can be demonstrated in the majority of, if not all, patients with schizophrenia. When unaffected co-twins of patients with schizophrenia were compared with twins who were both normal, no differences were observed, suggesting that nongenetic factors are important in the cause of the prefrontal physiologic deficit that appears to characterize schizophrenia. When concordant twins with a high- vs a low-dose lifetime history of neuroleptic treatment were compared, the twin receiving the higher dose was more hyperfrontal in six of eight pairs, suggesting that long-term neuroleptic treatment does not play a major role in hypofrontality.

Adult↗
PubMed1992

Dichotic listening in monozygotic twins discordant and concordant for schizophrenia.

Emotional and neutral word versions of the fused rhymed words dichotic listening test were administered to members of 18 pairs of monozygotic twins discordant for schizophrenia, 7 pairs concordant for schizophrenia, and 7 pairs of normal twins. In the discordant group, affected twins had smaller right ear advantages than did their unaffected cotwins for neutral words. The difference was completely attenuated with the presentation of emotional words or in less powerful between-group comparisons that included twins concordant for schizophrenia and normal twins. It is unlikely that this finding reflects an abnormality in the lateralized representation of language, both because we did not find a correlation between handedness scores and dichotic listening scores and because emotional stimuli normalized results. The finding may reflect abnormalities in the allocation of attention for priming language centers in the left hemisphere. 'At risk' subjects, i.e., the unaffected members of the discordant pairs, did not differ significantly from normal monozygotic twins on measures of dichotic listening.

Adult↗
PubMed1992

Are we overestimating the genetic contribution to schizophrenia?

That genetic factors contribute to the etiology of schizophrenia is no longer debated; the nature and magnitude of that contribution, however, are still open for discussion. In this article, concordance rates for twin studies of schizophrenia are reviewed as one means of assessing the magnitude of the genetic contribution. Using only those studies in which representative samples were used and zygosity was determined with reasonable certainty, the pairwise concordance rate for schizophrenia was found to be 28 percent for monozygotic (MZ) and 6 percent for dizygotic (DZ) twins. Review of twin studies of other central nervous system diseases reveals that schizophrenia is most similar to multiple sclerosis (MZ concordance rate 27%). Although genetics remains as the single most clearly defined etiological factor in schizophrenia, the question remains whether we are overestimating the magnitude of the genetic contribution.

Central Nervous System Diseases↗
PubMed1992

Second-trimester markers of fetal size in schizophrenia: a study of monozygotic twins.

OBJECTIVE: Since the second prenatal trimester is the critical period of massive neural cell migration to the cortex, and fingertip dermal cells migrate to form ridges during this same period, the authors sought to determine whether there are differences in fingertip ridge count in pairs of monozygotic twins discordant for schizophrenia, possibly indicating that a prenatal anatomical insult affected the twins differently. METHOD: The fingertip dermal ridges of 30 pairs of monozygotic twins (23 pairs in which the twins were discordant for schizophrenia and seven pairs in which both twins were normal) were counted by two persons trained in anthropometric research. Intrapair differences in the counts were then measured, and the differences among the pairs of normal twins were compared with the differences among the pairs discordant for schizophrenia. RESULTS: The twins discordant for schizophrenia had significantly greater absolute intrapair differences in total finger ridge count and significantly greater percent intrapair differences than the normal twins; i.e., their fingerprints were significantly less "twin-like." CONCLUSIONS: The study suggests that various second-trimester prenatal disturbances in the epigenesis of one twin in a pair discordant for schizophrenia may be related to the fact that only one of the twins expresses his or her genetic predisposition toward schizophrenia. This is consistent with a "two-strike" etiology of schizophrenia: a genetic diathesis plus a second-trimester environmental stressor.

Adult↗
PubMed1992

Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins.

OBJECTIVE: The authors previously reported that in monozygotic twins discordant for schizophrenia the affected twin almost invariably had a smaller anterior pes hippocampus, measured with magnetic resonance imaging (MRI), and invariably had less regional cerebral blood flow (rCBF) in the dorsolateral prefrontal cortex during performance of the Wisconsin Card Sorting Test. The present study was an investigation of the relationship between hippocampal pathology and prefrontal hypofunction in the same twin pairs. METHOD: Nine pairs of monozygotic twins discordant for schizophrenia underwent MRI scanning for determination of anterior hippocampal volume and xenon-inhalation rCBF testing for determination of prefrontal physiological activation associated with the Wisconsin Card Sorting Test. RESULTS: The differences within twin pairs on the MRI and rCBF measures were strongly and selectively correlated. Specifically, the more an affected twin differed from the unaffected twin in left hippocampal volume, the more they differed in prefrontal physiological activation during the Wisconsin Card Sorting Test. In the affected twins as a group, prefrontal activation was strongly related to both left and right hippocampal volume. These relationships were not found in the group of unaffected twins. CONCLUSIONS: This finding is consistent with the notion that schizophrenia involves pathology of and dysfunction within a widely distributed neocortical-limbic neural network that has been implicated in, among other activities, the performance of cognitive tasks requiring working memory.

Adult↗
PubMed1991

Subtle signs of prenatal maldevelopment of the hand ectoderm in schizophrenia: a preliminary monozygotic twin study.

Genes that predispose to psychosis may act by making individuals more vulnerable to the disruptive effects of various prenatal insults. Fetal organogenesis is mostly completed in the first prenatal trimester. The second trimester is a critical period of massive neuronal migration from the periventricular germinal matrix to the cortex. A peripheral appendage developing simultaneously with this neural migration to the cortex is the distal upper limb. The ectodermal cells of the fetal upper limb migrate to form the hand skin during the fourth and fifth months of gestation (first two-thirds of the second prenatal trimester). Discrepancies in hand morphology between two identical (monozygotic [MZ]) co-twins may be temporal markers, that is, the "fossilized" evidence of various ischemic and other nongenetic insults that may have affected one fetus more than his MZ co-twin during that early part of the second trimester. In twins, prenatal insults (e.g., ischemia) frequently do not affect both co-twins to the same extent, so we examined seven putative markers of prenatal injury to the hand in 24 MZ twin pairs discordant for schizophrenia or delusional disorder. Compared with well co-twins, the affected co-twins had significantly higher total scores of fourth- and fifth-month dysmorphological hand anomalies.

Delusions↗
PubMed1991

A viral-anatomical explantation of schizophrenia.

Recent neuropathological and neuroradiological studies of schizophrenia have pointed to the medial temporal cortex, especially the hippocampus, parahippocampal gyrus, and amygdala, as the areas primarily affected by this disease. Localization of the disease process to these structures may be explained anatomically because they are immediately contiguous to the foramen rotundum. Some viruses are known to ascend the trigeminal nerve and enter the cranial cavity through the foramen rotundum. They might latently infect the medial temporal cortex and be reactivated in early adulthood, producing the symptoms of schizophrenia. The distance from the nasal mucosa to the medial temporal cortex is less than 2 cm in infants. An anatomical explanation of schizophrenia could account for the seasonality of schizophrenic births, the observed excess birth trauma in schizophrenic individuals, the clinical aspects of schizophrenia, such as auditory hallucinations, and the genetic component of the disease.

Encephalitis↗
PubMed1990

Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia.

Recent neuroradiologic and neuropathological studies indicate that at least some patients with schizophrenia have slightly enlarged cerebral ventricles and subtle anatomical abnormalities in the region of the anterior hippocampus. Using magnetic resonance imaging (MRI), we studied 15 sets of monozygotic twins who were discordant for schizophrenia (age range, 25 to 44 years; 8 male and 7 female pairs). For each pair of twins, T1-weighted contiguous coronal sections (5 mm thick) were compared blindly, and quantitative measurements of brain structures were made with a computerized image-analysis system. In 12 of the 15 discordant pairs, the twin with schizophrenia was identified by visual inspection of cerebrospinal fluid spaces. In two pairs no difference could be discerned visually, and in one the twin with schizophrenia was misidentified. Quantitative analysis of sections through the level of the pes hippocampi showed the hippocampus to be smaller on the left in 14 of the 15 affected twins, as compared with their normal twins, and smaller on the right in 13 affected twins (both P less than 0.001). In the twins with schizophrenia, as compared with their normal twins, the lateral ventricles were larger on the left in 14 (P less than 0.003) and on the right in 13 (P less than 0.001). The third ventricle also was larger in 13 of the twins with schizophrenia (P less than 0.001). None of these differences were found in seven sets of monozygotic twins without schizophrenia who were studied similarly as controls. We conclude that subtle abnormalities of cerebral anatomy (namely, small anterior hippocampi and enlarged lateral and third ventricles) are consistent neuropathologic features of schizophrenia and that their cause is at least in part not genetic. Further study is required to determine whether these changes are primary or secondary to the disease.

Adult↗