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Biomedical subjects

W G Honer

Publications and source records attributed to W G Honer.

At least 91 records · Page 5Linked to original sources
PubMed1995

Obstetric complications and severity of illness in schizophrenia.

A history of obstetric complications (OCs) is common in schizophrenia and may lead to a severe form of the disorder. In order to test this possibility, three questions were identified: (1) Is a history of OCs in schizophrenia common in patients with a severe form of illness? (2) Do patients with OCs have more impaired function, greater severity of illness, and poorer treatment outcome than those with no identified OCs? (3) Are OCs associated with an early age at onset of illness? Obstetric history, clinical indices of functioning, and illness severity were obtained for 83 severely ill patients with schizophrenia. The proportion of patients with a history of OCs was greater in this study than has been reported previously. Subjects with a history of OCs had better functioning than those with no OCs at the time of admission but no group differences were found at discharge. No difference in age at onset of illness was found between patients with and without an OC history.

Activities of Daily Living↗
PubMed1995

A clinical study of clozapine treatment and predictors of response in a Canadian sample.

OBJECTIVE: To study the clinical response to clozapine in patients with refractory schizophrenia. METHOD: Open trial of clozapine in 61 consecutively-treated patients. RESULTS: Following clozapine, the level of function of patients was improved relative to admission (p = 0.0001) and to the highest level in the previous year (p = 0.0001). Severity of illness was decreased (p = 0.0001). Overall, 31% of the patients were classified as responders to clozapine and the responders were all identified by 32 weeks of treatment. Poor functioning in the previous year was associated with less favourable response. At a mean interval of 26 months following discharge, 72% of the patients were continuing clozapine treatment. CONCLUSIONS: This open trial of patients who were treated consecutively indicates a comparable degree of response to clozapine as observed in controlled clinical trials, and that level of functioning in the previous year was the best predictor of response.

Adolescent↗
PubMed1994

Synapse alterations in the hippocampal-entorhinal formation in Alzheimer's disease with and without Lewy body disease.

We quantified by microdensitometry the immunoreactivity (IR) to monoclonal antibodies (SP6, SP12, SP15 and SP18) against various synaptic proteins in the molecular layers of the dentate gyrus, CA4, CA3, CA1, subiculum and entorhinal cortex in Alzheimer's disease (AD), Lewy body variant of AD (LBV) and diffuse Lewy body disease (DLBD). A significant decrease in SP6 IR was observed in almost all regions in AD (28.4-70.1%, mean 41.3%), LBV (19.0-42.5%, mean 26.8%) and DLBD (19.9-31.7%, mean 27.1%) compared to controls. In addition, SP6 IR in the outer molecular layer of the dentate gyrus was strongly correlated with tangle count in the entorhinal cortex (r = -0.70, P < 0.002), suggesting loss of perforant pathway projection. Although the decrease in SP12 and SP15 IR was less pronounced, the mean values were decreased in dementia. Furthermore, SP12 and SP15 labeled a large number of neuritic plaques, and SP15 occasionally stained cortical LBs. The present findings indicate (i) that in the hippocampal-entorhinal formation, the decrease of synapse protein IR in AD is more severe than that in LBV and DLBD, (ii) that synaptic markers detect a subset of dystrophic neurites in the plaques and (iii) that synapse proteins are involved in the formation of cortical LBs.

Aged↗
PubMed1994

Temporal lobe abnormalities in multigenerational families with schizophrenia.

Brain structure in familial schizophrenia was studied with computerized tomography in 42 individuals from six multigenerational families. Sulcal enlargement in the lateral temporal cortex, and ventricular and cisternal enlargement in the medial temporal region were observed in psychotic individuals compared to unaffected family members. Genetic factors in familial schizophrenia may exert part of their effect through determining or altering temporal lobe structure.

Adult↗
PubMed1994

Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease.

Glucose metabolism is depressed in the temporal and parietal regions of the cortex in patients with Alzheimer's disease. We measured the concentrations of two glucose transporters, GLUT1 and GLUT3, in six regions of brains from both control subjects and patients with Alzheimer's disease. The concentrations of both transporters were reduced in the cerebral cortex, with larger and highly significant reductions observed for GLUT3, the putative neuronal glucose transporter. The reductions in GLUT3 were greater than the loss of synapses, and should be considered as a potential cause of the deficits in glucose metabolism.

Adult↗
PubMed1994

Topographical distribution of synaptic-associated proteins in the neuritic plaques of Alzheimer's disease hippocampus.

Studies of the molecular composition of the abnormal neuritic processes of the plaques in Alzheimer's disease (AD) have shown that these structures are immunoreactive with antibodies against growth-related molecules, synaptic/axonal proteins, and cytoskeletal proteins. These studies suggest that a subpopulation of abnormal neurites in the plaque are sprouting axons that eventually degenerate. To test this hypothesis further we studied the regional distribution of plaques in the hippocampus using a panel of monoclonal antibodies against synaptic proteins. With these antibodies we found a greater proportion of immunoreactive plaques compared to previous studies where a monoclonal antibody against synaptophysin was used. The most sensitive antibodies to detect neuritic plaques were SP11 and anti-p65, and the largest number of positive plaques was found in the entorhinal cortex and CA1 region. These results further support the theory that synaptic and axonal damage are involved in plaque formation in AD.

Aged↗
PubMed1994

Hippocampal synaptic pathology in patients with temporal lobe epilepsy.

Immunostaining of synaptic terminals was studied in the hippocampus of 26 patients who had surgical resections for intractable temporal lobe epilepsy. Two monoclonal antibodies (EP10 and SP12) reactive with distinct synaptic antigens were used on paraffin-embedded tissues. The results indicated qualitative reductions on synaptic terminals in CA4 and other regions where cell loss is reported. The inner molecular layer of the dentate gyrus was observed to have increased synaptic immunostaining. Synaptic terminal loss in CA4 and redistribution in the molecular layer were most frequent in cases with hippocampal sclerosis. However, both forms of synaptic pathology were also noted in most cases where the pathological findings were classified as indefinite, and in some cases associated with mass lesions of the temporal lobe. These results support the importance of neuronal loss and synaptic reorganization as possible mechanisms of illness in epilepsy. They also indicate that synaptic immunostaining may be a useful adjunct to routine neuropathological diagnostic techniques.

Adolescent↗
PubMed1994

Olfactory hallucinations and olfactory identification ability in patients with schizophrenia and other psychiatric disorders.

Olfactory identification ability and the prevalence of olfactory hallucinations were examined in 183 hospitalized patients from three diagnostic groups. One hundred and thirty-one patients with schizophrenia, 21 patients with major depression, 31 women with eating disorders along with 77 normal control subjects were examined using the University of Pennsylvania Smell Identification Test (UPSIT) and were questioned regarding the presence of olfactory hallucinations. Olfactory identification deficits were observed only in patients with schizophrenia. In contrast, olfactory hallucinations were reported by members of all psychiatric diagnostic categories (34.6% of patients with schizophrenia; 19% of depressed patients and 29% of eating disorders patients). For patients with schizophrenia, women were more likely to report olfactory hallucinations and had higher UPSIT scores than men.

Adolescent↗
PubMed1994

Testing Liddle's three-syndrome model in families with schizophrenia.

While the symptoms of schizophrenia can be grouped into positive and negative syndromes, increasing evidence suggests that three clusters of symptoms are present. Liddle (1987a) described a three-syndrome model comprised of reality distortion, psychomotor poverty and disorganization symptom clusters. This model was assessed in the present study using a sample of 72 members of five families segregating schizophrenia. A wide range of psychopathology was present across a spectrum of diagnoses. Data on symptoms used in Liddle's model were derived from the Positive and Negative Syndrome Scale (PANSS) and a mental status examination. Factor analysis of the data indicated the presence of three clusters of symptoms. The psychomotor poverty or negative symptom cluster was confirmed in the familial sample. However, the other two factors differed somewhat from the Liddle model. Hallucinations, delusions, disorganized thinking and inappropriate affect formed one factor; suspiciousness and stereotyped thinking formed the other. These three symptom clusters may be comparable to the catatonic, hebephrenic and paranoid classical subtypes of schizophrenia. The implications of Liddle's model for genetic studies of schizophrenia require further investigation.

Adult↗
PubMed1994

New perspectives on the clinical neurobiology of treatment response in schizophrenia.

A structured approach is used to review the rapid progress in neurobiology related to treatment response in schizophrenia. Findings are presented and discussed according to the molecular, cellular and regional levels of brain organization. The genotype-phenotype structure is used to consider potential interactions between genes, clinical manifestations of the illness and treatment response. The integration of neurobiological research into the future development of new treatment strategies for schizophrenia holds significant promise.

Animals↗
PubMed1994

Results of computerised tomography during first admission for psychosis.

A cohort of 168 psychotic patients underwent computerised tomography (CT) during their first admission. Cortical atrophy was present in 40% of patients. The frequency of atrophy increased with age, but did not differ between patients with schizophrenia, schizoaffective disorder, bipolar disorder or psychotic depression. Other CT findings of note were present in 6.6% of patients, and included four infarctions, three arachnoid cysts, and one each of venous angioma, colloid cyst, cavum vergae and post-traumatic changes. The frequency of CT findings other than atrophy was increased in the psychotic depression group. The findings support the proposal of the onset of psychosis being an indication for CT.

Adolescent↗
PubMed1994

Diagnostic reassessment and treatment response in schizophrenia.

BACKGROUND: The reasons for poor treatment response in some patients with schizophrenia remain unclear. It is possible that misdiagnosis of nonschizophrenic disorders as schizophrenia could result in suboptimal pharmacotherapy in some patients. METHOD: To assess this possibility, 110 severely ill, chronic patients with a referral diagnosis of schizophrenia were comprehensively assessed and rediagnosed according to DSM-III-R criteria. Global Assessment of Function (GAF) and Clinical Global Impressions (CGI) ratings were made at admission and at discharge from the ward, after the implementation of individualized treatment plans. RESULTS: The diagnosis of schizophrenia was confirmed in 80 patients (73%) and revised to another type of psychotic illness in 30 patients (27%). The GAF and CGI ratings were similar at admission in patients with confirmed and revised diagnoses. All patients improved by the time of discharge (p = .0001); however, patients with a revised diagnosis improved more than those with confirmed schizophrenia (p = .02). Patients with a revised diagnosis were less likely to require continued hospitalization on chronic care wards (p = .004). At admission, medication regimens were similar in the two groups of patients. At discharge, patients with a revised diagnosis were less likely to have received neuroleptics (p = .007) and more likely to have received antimanic drugs (p = .0002) or electroconvulsive therapy (p = .0004). CONCLUSION: These findings from a clinical sample suggest that diagnostic reassessment is an important first step in the management of apparently refractory schizophrenia.

Adolescent↗
PubMed1994

Evidence for anticipation in schizophrenia.

Anticipation, or increasing severity of a disorder across successive generations, is a genetic phenomenon with an identified molecular mechanism: expansion of unstable trinucleotide repeat sequences. This study examined anticipation in familial schizophrenia. Three generations of siblines from the affected side of families selected for unilineal, autosomal dominant-like inheritance of schizophrenia were studied (n = 186). Across generations more subjects were hospitalized with psychotic illness (P < .001), at progressively earlier ages (P < .0001), and with increasing severity of illness (P < .0003). The results indicate that anticipation is present in familial schizophrenia. These findings support both an active search for unstable trinucleotide repeat sequences in schizophrenia and reconsideration of the genetic model used for linkage studies in this disorder.

Adolescent↗
PubMed1993

Human synaptic proteins with a heterogeneous distribution in cerebellum and visual cortex.

Synaptic pathology is likely to be an important feature of a number of neuropsychiatric illnesses. An antibody called EP10 was used previously to demonstrate a regional reduction in a 38 kDa synaptophysin-like protein in Alzheimer's disease. The SP antibodies were developed for further study of this and other synaptic proteins in human brain. Human brain proteins immunoprecipitated with EP10 were used as the immunogen. Hybridoma screening was carried out with a sequential ELISA-immunocytochemical approach. Sixteen antibodies were obtained, the antigens clustered into five groups. Five antibodies were reactive with a 38 kDa synaptophysin-like protein. Another two antibodies were reactive with a 16 kDa antigen which may be synaptobrevin. Immunocytochemical studies indicated these two antigens appeared to be co-localized in human brain. Four antibodies were reactive with a distinct, 34-36 kDa antigen. In the cerebellum, this antigen was restricted to terminals in the molecular layer, putatively in the parallel fibre synapses. Two antibodies were reactive with a 26-27 kDa antigen. In the cerebellum, this antigen localized to a subset of terminals which included the axo-axonal contacts of the Basket and Purkinje cells. The final group of three antibodies detected a complex group of 38 kDa. 40 kDa and higher molecular weight antigens. The results suggest that heterogeneity among synapses can be defined through antibodies directed against distinct proteins. The SP antibodies may be useful probes for studies of human synaptic proteins, and for studies of pathological conditions which disrupt these molecules.

Animals↗
PubMed1993

Positive and negative symptoms in families with schizophrenia.

Positive and negative symptoms are measurable characteristics that may represent core features of schizophrenia and offer a quantitative approach for studying the genetics of schizophrenia and related disorders. The Positive and Negative Syndrome Scale (PANSS) was used to assess 72 members of five families segregating schizophrenia. The study confirmed high internal reliability of PANSS scales in this sample with diverse lifetime diagnoses. Gender but not alcoholism affected scores. Schizophrenia/schizoaffective and schizophrenia spectrum disorder groups had higher mean scores for the positive and negative scales than other lifetime diagnostic groups, consistent with genetic transmission of these symptoms. Positive and negative symptom patterns did not subtype families. The results support the validity of positive and negative symptom measures as independent dimensions in familial schizophrenia.

Adolescent↗