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Biomedical subjects

W G Honer

Publications and source records attributed to W G Honer.

At least 19 recordsLinked to original sources
PubMed1999

No evidence for astrogliosis in brains of schizophrenic patients. A post-mortem study.

Schizophrenia is clinically and neuropsychologically characterized by severe cognitive and functional impairment suggesting the presence of a neurodegenerative process in the brains of affected individuals. A variety of neuroanatomical changes have been described such as loss and disorientation of neurons in grey and white matter and cortical atrophy. However, the neuropathological basis for schizophrenia is still unclear. In the present study we monitored the density of GFAP-positive astrocytes in brains of 33 schizophrenic patients and 26 healthy controls. Both grey matter (entorhinal cortex and subiculum) and white matter (premotor cortex, subventricular zone of the third ventricle and next to inferior horn) structures were measured bilaterally. The overall finding was that there is no evidence for increased astrogliosis in brains of schizophrenic patients vs healthy controls. Therefore, degeneration is unlikely to be the main neuropathological mechanism in schizophrenic brains.

Astrocytes↗
PubMed1999

Assessing the machinery of mind: synapses in neuropsychiatric disorders.

Neural connectivity in postmortem human brain can now be studied with the use of antibodies that react with synapse-enriched proteins. Using a range of antibody-based techniques, the authors observed abnormalities in connectivity in Alzheimer's disease, temporal lobe epilepsy, and schizophrenia. They also found disease-related differences in the individual protein markers affected and in the anatomical distribution of differences from controls. Molecular and cellular abnormalities in neural connectivity may underlie functional abnormalities observed in vivo using positron emission tomography or functional magnetic resonance imaging.

Humans↗
PubMed1998

No evidence for linkage of the CHRNA7 gene region in Canadian schizophrenia families.

Schizophrenia patients demonstrate a deficiency in the filtering of sensory information, and one specific measure involves a response to the second of a pair of auditory stimuli. A neurophysiological measure of this consists of the electroencephalographic response to pairs of auditory signals, emitted fractions of a second apart. Schizophrenic patients and some of their unaffected relatives show a failure of inhibition of a second tone if it occurs 50 msec after the first. A recent genome scan indicated that the gating defect is linked to the alpha 7 neuronal nicotinic acetyl choline receptor gene on chromosome 15. We genotyped 5 schizophrenia families with a total of 96 subjects with a dinucleotide polymorphic marker located less than 120 kb from the first exon of the alpha 7 neuronal nicotinic acetylcholine receptor gene. Linkage analysis was undertaken using parametric and nonparametric statistical methods. The results of the parametric analysis showed negative lod scores under both narrow and broad diagnosis (lod = -3.6 and -4.8, respectively, at theta = 0), and dominant and recessive modes of transmission of the disease. Nonparametric analysis using GENEHUNTER produced nonsignificant NPL scores (NPL = -0.4 and -0.3 for broad and narrow diagnoses, respectively). In summary, we did not find any evidence that the alpha 7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is linked to schizophrenia. However, we have not been able to assess the P50 measures in these families.

Chromosomes, Human, Pair 15↗
PubMed1998

Left nostril olfactory identification impairment in a subgroup of male patients with schizophrenia.

Abnormal structural brain asymmetries have been reported in schizophrenia in brain areas which overlap with olfactory processing regions, with abnormalities more often described within the left hemisphere. We attempted to determine whether the olfactory agnosia observed in some male patients with schizophrenia was more likely left-hemisphere based. We assessed unirhinal (single nostril) olfactory identification and detection threshold in 65 male patients who met DSM-IV criteria for the diagnosis of schizophrenia and 59 healthy male control subjects. A two-way, mixed-design ANCOVA with diagnosis as the between-group factor, nostril as the within-subject factor and age as covariate was used to compare olfactory identification ability. This analysis demonstrated that patients with schizophrenia performed more poorly than the healthy controls across nostrils, but no differences were observed in either group between nostrils. However, when patients were classified according to unirhinal olfactory status (impaired left < right, impaired right < left, normosmic left < right, normosmic right < left), impaired patients were more than twice as likely to be classified as having a left nostril disadvantage than right nostril disadvantage. In contrast, within the normosmic group of patients, this pattern was reversed. Moreover, when those patients whose unirhinal olfactory scores differed by less than two points were removed from the analysis, a 2:1 ratio of left < right versus right < left was observed in the impaired patients. These results suggest that for impaired male patients with schizophrenia, olfactory identification deficits are more likely found for the left nostril, perhaps indicative of abnormalities in olfactory processing within the left hemisphere.

Adolescent↗
PubMed1998

Localization of a novel septin protein, hCDCrel-1, in neurons of human brain.

Synaptic function is critical for cell-cell communication and the characterization of proteins that function during vesicle formation, transport and fusion events will yield further insight into the mechanisms of synaptic transmission. We have cloned and characterized a gene product expressed in human brain called hCDCrel-1. This protein is a new member of the septin family of gene products that functions during cytokinesis in lower eukaryotes. In this study we characterize the expression of the hCDCrel-1 gene and localize the hCDCrel-1 protein to neurons in adult human brain. hCDCrel-1 co-purifies with SNAP-25 and synaptophysin marked synaptosomes, suggesting a novel function for this gene family in the brain. Our data indicate that members of the septin family of proteins may function in synaptic vesicle transport, fusion or recycling events in the human brain.

Adult↗
PubMed1998

Compartmental volumetry of the superior temporal gyrus reveals sex differences in schizophrenia--a post-mortem study.

Brain imaging studies have shown superior temporal gyrus (STG) volume loss and abnormal patterns of asymmetry in schizophrenia; however, these are not consistent findings. Post-mortem volumetry of three different STG regions (defined by external landmarks) was used to compare 17 schizophrenics to 20 age- and sex-matched controls. Total STG volumes did not differ. A significant gray-matter volume reduction in schizophrenics was observed in the middle compartment (reaching from the mamillary body to the lateral geniculate body). This may have been related to reduced length of this region, particularly in schizophrenic females. These results reflect the problematic issue of defining boundaries of macroscopic brain structures.

Analysis of Variance↗
PubMed1998

Olfactory deficits in patients with schizophrenia and severe polydipsia.

BACKGROUND: The present study was designed to assess olfactory function in severely polydipsic/hyponatremic patients with schizophrenia who also had intermittent water intoxication. METHODS: The University of Pennsylvania Smell Identification Test and an olfactory acuity battery were administered to three groups of male subjects: 9 patients with schizophrenia and severe polydipsia/hyponatremia, 9 control nonpolydipsic/normonatremic patients with schizophrenia, and 9 normal controls. RESULTS: Male patients with severe polydipsia/hyponatremia and intermittent water intoxication had marked olfactory acuity and identification deficits when compared to the patient control group of similar age and age at illness onset, and to normal controls. CONCLUSIONS: The finding of deficient acuity (detection threshold) in the polydipsic/hyponatremic group but not the nonpolydipsic, normonatremic group suggests that for this subgroup, abnormalities of olfactory sensory function may occur in a pattern previously reported for other brain disorders such as Alzheimer's disease.

1-Butanol↗
PubMed1998

Obstetric complications, treatment response and brain morphology in adult-onset and early-onset males with schizophrenia.

BACKGROUND: Substantial variability in age at onset of illness and course of illness exists between patients with schizophrenia. Recent studies suggest that age at illness onset may be useful in defining biologically and clinically distinct subgroups of patients. METHODS: Two hundred and ten males with schizophrenia were classified as early-onset or adult-onset according to their age at first hospitalization. Birth history, clinical functioning and treatment response was assessed in a subgroup of patients. Brain anatomy was assessed from CT scans in all patients and in 32 non-psychiatric control subjects. RESULTS: Patients with an early-onset were likely to have a history of obstetric complications, a poor response to neuroleptic treatment, and showed no relationship between ventricle size and duration of illness. Adult-onset patients were less likely to have obstetric complications, more likely to respond to treatment in the first years of illness, and showed an association between brain structure and duration of illness. CONCLUSIONS: The distinction between early- and adult-onset patients may have important aetiological and treatment implications.

Adolescent↗
PubMed1998

An open comparison of clozapine and risperidone in treatment-resistant schizophrenia.

BACKGROUND: Clozapine and risperidone are used in treatment-resistant schizophrenia. At present, there are few reported comparisons of these drugs in this population. We report on a consecutive series of treatment-resistant schizophrenics given either clozapine or risperidone in open clinical trials. METHOD: Subjects were treated with clozapine (n = 57) or risperidone (n = 29). Pretreatment GAF, CGI, and PANSS scores did not differ between the groups, nor did demographic variables including age, age at first hospitalization, years ill, number of previous hospitalizations, or gender. The mean treatment trial was 12.1 weeks, with mean doses of clozapine 420 mg, and risperidone 7.75 mg. The length of the trial did not differ significantly between the groups. Response was taken to be a 20% decrease in the PANSS score. RESULTS: Using repeated measures ANOVA, PANSS total scores (F = 5.3, p = 0.02) and positive subscore (F = 7.4, p = 0.008) showed greater improvement in the clozapine group than the risperidone group, while other PANSS subscores showed a trend toward greater improvement with clozapine. The PANSS-derived factors of excitement (F = 6.7, p = 0.01), psychosocial withdrawal (F = 3.8, p = 0.05), and psychomotor retardation (F = 3.9, p = 0.05) improved more in the group treated with clozapine. The GAF (F = 10.9, p = 0.0014), CGI (F = 11.5, p = 0.0011), and CGI improvement (p = 0.0001) scores also improved more in the clozapine group. Of the clozapine group, 25 (44%) responded, while 8 (28%) of the risperidone group responded to treatment. DISCUSSION: Clozapine had better efficacy in subjects with treatment-resistant schizophrenia compared to risperidone, although risperidone appears to yield better response rates than those previously reported for typical antipsychotics. Double-blind, controlled trials of risperidone are needed to establish its efficacy in treatment-resistant schizophrenia.

Adult↗
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

Absence of linkage for schizophrenia on the short arm of chromosome 5 in multiplex Canadian families.

A VNTR for the human dopamine transporter gene (DAT-1) has been localized to chromosome 5p15.3. Silverman et al. [1996] found evidence for genetic linkage of the D5S111 locus, located just centromeric to DAT-1, to schizophrenia and related disorders in a large Hispanic family. We evaluated five markers on 5p, including D5S111 and the DAT-1 VNTR, in five multiplex schizophrenic families, assuming autosomal dominant transmission (subjects assessed n = 122, DNAs available n = 96, individuals with schizophrenia and schizoaffective disorder n = 36, broader spectrum disorders n = 14). LOD scores were negative across all families for all markers tested, and overall LOD scores were strongly negative (<-2.0, theta = 0) across all five families for each of the markers typed. Thus, there is no evidence to support the linkage of markers in this region of chromosome 5 to schizophrenia in this sample of families.

Canada↗
PubMed1997

Increased concentrations of presynaptic proteins in the cingulate cortex of subjects with schizophrenia.

BACKGROUND: Cytoarchitectural and neurochemical studies demonstrate disorganization in the cerebral cortex in schizophrenia, which perhaps underlies the severe behavioral disturbances of the disease. This neuronal disarray should be accompanied by synaptic abnormalities. As such, presynaptic proteins have proved valuable indexes of synaptic density and their concentrations have correlated markedly with synaptic loss. Our study sought to determine whether abnormalities exist in the concentrations of presynaptic proteins in the postmortem cerebral cortex of subjects with schizophrenia. METHODS: Presynaptic protein immunoreactivities were assessed in 4 different cerebrocortical regions derived from 16 elderly controls, 19 elderly subjects with schizophrenia, and 24 subjects with Alzheimer's disease. Tissues were assayed with the monoclonal antibodies EP10 and SP4, which recognize synaptophysin, and the monoclonal antibodies SP6 and SP14, which detect syntaxin and synaptosomal-associated protein-25-kd immunoreactivities, respectively. RESULTS: In subjects with schizophrenia relative to controls, presynaptic proteins were increased in the cingulate cortex, but were unchanged in the temporal, frontal, and parietal cortices. In contrast, when cases with Alzheimer's disease were compared with controls, presynaptic proteins were decreased in the frontal, temporal, and parietal samples. CONCLUSIONS: These findings reveal changes in the synaptic organization of the cingulate cortex in schizophrenia relative to other areas examined. These changes are distinct from the deficits in presynaptic proteins observed in Alzheimer's disease.

Alzheimer Disease↗
PubMed1997

The use of risperidone in severely demented patients with persistent vocalizations.

OBJECTIVE: The hypothesis being tested was that low doses of risperidone would diminish persistent, purposeless vocalizations in two severely demented geriatric women. A secondary hypothesis was that the severe tardive dyskinesia observed in one patient would improve after risperidone treatment. DESIGN: An intrasubject on-off-on design was employed. SETTING: A chronic care facility in Canada. SUBJECTS: Two inpatients with DSM-IV (American Psychiatric Association) diagnosis of combined Alzheimer vascular dementia. MEASURES: Nursing assessment of frequency of vocalizations. Extrapyramidal System Rating Scale (ESRS) and Folstein Mini Mental State Examination (MMSE). RESULTS: With risperidone treatment, the vocalizations diminished to less than 20% of baseline ratings. For the patient with dyskinesia, ESRS dyskinetic movement scores decreased (baseline = 27; after risperidone 8 weeks = 16). No change was observed for the MMSE. CONCLUSIONS: The findings support the main hypothesis. The secondary hypothesis was also supported. Further studies of larger numbers of subjects are required to substantiate these preliminary findings.

Aged↗
PubMed1997

Cholinergic fibre loss associated with diffuse plaques in the non-demented elderly: the preclinical stage of Alzheimer's disease?

Diffuse plaques are the earliest Alzheimer-type lesions in Down's syndrome and are a putative marker for the preclinical stage of Alzheimer's disease (AD). As a cerebral cortical cholinergic deficit is one of the characteristics which defines AD, we examined the brains of individuals who had died without a history of neurological disease to determine whether this deficit is present in association with diffuse plaques. Of the 24 cases collected, 14 were older than 60 years of age (mean 69.2 years) and 10 were younger (mean 29.6 years). Of the 14 older cases, 9 had diffuse plaques in the entorhinal cortex (ECx) and/or inferior temporal gyrus (ITG). The older cases were divided into two groups (plaque-positive or plaque-negative cases). These groups did not differ significantly with respect to age, post-mortem delay, synaptophysin immunoreactivity or neurofibrillary tangle density. Cholinergic fibre densities were estimated in sections stained using acetylcholinesterase (AChE) enzyme histochemistry. Mean AChE fibre density was decreased in both the ITG and ECx (approximately 30% and 50% depletion, respectively) in the plaque-positive group compared to the plaque-negative group and in both areas the mean fibre density of the plaque-positive group was about 50% of that in the younger group. These results suggest that diffuse plaques in the non-demented elderly are associated with an accelerated age-related cortical cholinergic deficit and, therefore represent the preclinical stage of AD.

Adult↗
PubMed1997

Cingulate cortex synaptic terminal proteins and neural cell adhesion molecule in schizophrenia.

The neuronal organization and patterns of afferent innervation are abnormal in the cingulate cortex in schizophrenia, and associated changes in synaptic terminals could be present. A panel of monoclonal antibodies was defined with biochemical and fusion protein studies as detecting syntaxin (antibody SP6), synaptophysin (antibody SP4) and synaptosomal-associated protein-25 (antibody SP12). These antibodies and a polyclonal antibody reactive with neural cell adhesion molecule were used to investigate the cingulate cortex in schizophrenia. Immunocytochemistry indicated that syntaxin immunoreactivity had a considerably wider distribution than synaptophysin. Overall, multivariate analysis indicated increased synaptic terminal protein immunoreactivity in schizophrenia compared to controls (P=0.004). Controlled for age and post mortem interval, syntaxin immunoreactivity was significantly elevated in schizophrenia (P=0.004), and neural cell adhesion molecule immunoreactivity was also elevated (P=0.05). The neural cell adhesion molecule to synaptophysin ratio was increased (P=0.005), possibly indicating the presence of less mature synapses in schizophrenia. Elevated syntaxin immunoreactivity is consistent with increased glutamatergic afferents to the cingulate cortex in schizophrenia, and combined with the neural cell adhesion molecule to synaptophysin ratio results suggests that synaptic function in this region in schizophrenia may be abnormal.

Antigens↗
PubMed1997

NCAM and schizophrenia: genetic studies.

The hypothesis of a neurodevelopmental dysfunction being involved in the etiology of schizophrenia is suggested by the observation of morphological alterations in the brains of schizophrenia patients. These alterations may be caused by defects in neural cell differentiation or migration, which could lead to disrupted neuronal circuitry and to the schizophrenia symptomatology. The neural cell adhesion molecule (NCAM) plays a major role in cell migration and axon outgrowth, and is involved in synaptic plasticity mechanisms implicated in adult cognitive functions. Altered levels of the NCAM polysialylated form, PSA-NCAM, in the brain of schizophrenia patients have been reported, and are supportive of a role for this molecule in the disorder. To investigate the possible involvement of the NCAM gene in schizophrenia, we conducted a comprehensive genetic study, which included linkage analysis and an association study employing the Haplotype Relative Risk (HRR) design in nuclear families. Our results indicate that structural alterations in the NCAM gene are unlikely to play a major role in schizophrenia, although a function for the NCAM molecule in the etiology of the disease remains an intriguing hypothesis.

Adult↗
PubMed1997

Use of a quantitative trait to map a locus associated with severity of positive symptoms in familial schizophrenia to chromosome 6p.

A number of recent linkage studies have suggested the presence of a schizophrenia susceptibility locus on chromosome 6p. We evaluated 28 genetic markers, spanning chromosome 6, for linkage to schizophrenia in 10 moderately large Canadian families of Celtic ancestry. Parametric analyses of these families under autosomal dominant and recessive models, using broad and narrow definitions of schizophrenia, produced no significant evidence for linkage. A sib-pair analysis using categorical disease definitions also failed to produce significant evidence for linkage. We then conducted a separate sibpair analysis using scores on positive-symptom (psychotic), negative-symptom (deficit), and general psychopathology-symptom scales as quantitative traits. With the positive symptom-scale scores, the marker D6S1960 produced P = 1.2 x 10(-5) under two-point and P = 5.4 x 10(-6) under multipoint analyses. Using simulation studies, we determined that these nominal P values correspond to empirical P values of .034 and .0085, respectively. These results suggest that a schizophrenia susceptibility locus on chromosome 6p may be related to the severity of psychotic symptoms. Assessment of behavioral quantitative traits may provide increased power over categorical phenotype assignment for detection of linkage in complex psychiatric disorders.

Canada↗