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R D Sanders

Publications and source records attributed to R D Sanders.

At least 37 records · Page 2Linked to original sources
PubMed1999

CAG repeat length in the hKCa3 gene and symptom dimensions in schizophrenia.

BACKGROUND: Long CAG repeats in the hKCa3 potassium channel gene have been associated with schizophrenia. We sought evidence for associations between this polymorphism and aspects of the schizophrenia phenotype. METHODS: Associations were investigated between CAG repeat length and gender, age of illness onset, and psychotic symptom dimensions in 203 unrelated individuals with DSM-IIIR schizophrenia. RESULTS: No association was found between CAG repeat length and gender or age of onset. Long CAG repeats were associated with higher negative symptom dimension scores. CONCLUSIONS: This study provides preliminary evidence that genetic liability to negative symptoms in schizophrenia may be partly mediated through the hKCa3 gene.

Adult↗
PubMed1999

A two-stage genome scan for schizophrenia susceptibility genes in 196 affected sibling pairs.

We undertook a systematic search for linkage in 196 affected sibling pairs (ASPs) with DSMIV schizophrenia. In stage 1 we typed 97 ASPs with 229 microsatellite markers at an average inter-marker distance of 17.26 cM. Multipoint affected sib pair analysis identified seven regions with a maximum lod score (MLS) at or above the level associated with a nominal pointwise significance of 5%, on chromosomes 2q, 4p, 10q, 15q, 18p, 20q and Xcen. In stage 2 we genotyped a further 54 markers in 196 ASPs together with parents and unaffected siblings. This allowed the regions identified in stage 1 to be typed at an average spacing of 5.15 cM, while the region of interest on chromosome 2 was typed to 9.55 cM. Analysis was performed on the whole data set. Simulation studies suggested that we would expect one multipoint MLS of 1.5 per genome scan in the absence of linkage. An MLS of 3 would be expected only once in every 20 genome scans and thus corresponds to a genome-wide significance of 0.05. We obtained three multipoint MLSs >1.5 and, on this basis, the results on chromosomes 4p, 18q and Xcen can be considered suggestive. However, none approached a genome-wide significance of 0. 05. The power of this study was >0.95 to detect a susceptibility locus of lambda(s)= 3 with a genome-wide significance of 0.05, but only 0.70 to detect a locus of lambda(s)= 2. Our results suggest that common genes of major effect (lambda(s)> 3) are unlikely to exist for schizophrenia.

Chromosome Mapping↗
PubMed1999

Dimensions of psychosis in affected sibling pairs.

Factor analytical studies of schizophrenia symptoms have consistently suggested three or more symptom dimensions, but it is not known whether any of these dimensions have a genetic basis. The purpose of this study was to investigate to what extent the dimensions show familial aggregation. Symptom ratings were made using the SAPS and SANS and the OPCRIT checklist on the members of 109 sibling pairs with DSM-IV schizophrenia or schizoaffective disorder. Factor analyses were performed on the ratings of both instruments, and correlations were made of within-pair factor scores. Analyses were also performed on the 89 pairs in which both members had a diagnosis of schizophrenia. Factor analysis of SAPS and SANS ratings resulted in positive, negative, and disorganization factors; analysis of OPCRIT ratings resulted in positive, negative, disorganization, and first-rank delusion factors. Only the disorganization dimension showed significant within-pair correlations, but these were of modest size and not significantly greater than the correlations for the other dimensions. None of the dimensions showed sufficient familial aggregation to suggest that they are close markers of genetic or common environmental factors that contribute liability to schizophrenia. They may be weakly associated with such factors and with factors that do not contribute liability to schizophrenia but do influence the form taken by the illness.

Adult↗
PubMed1999

An open trial of olanzapine in patients with treatment-refractory psychoses.

Olanzapine's structural similarities to clozapine and the results of premarketing clinical trials suggested potential usefulness in treating patients with treatment-refractory psychoses. Sixteen inpatients from the state hospital with severe, refractory schizophrenic or schizoaffective psychoses received olanzapine in a prospective, 12-week, open-label trial. The olanzapine dose was 10 mg/day for at least the first 6 weeks and never exceeded 20 mg/day. Mood stabilizers and other antipsychotic agents were discontinued before olanzapine was started. Patients frequently became more agitated within the first several weeks of initiating treatment, requiring the increased use of benzodiazepines and often leading to the discontinuation of olanzapine. Two patients improved significantly. Overall, significant clinical improvement was noted only for motor side effects. This study concluded that olanzapine was not effective in this heterogeneous group with chronic, severe, treatment-resistant psychosis when used in this manner. Further research is needed to explain the tendency toward agitation upon transition to olanzapine, which is reminiscent of reported risperidone complications. Clinicians should be alert for this complication and should minimize concomitant medication changes that might add to the risk of emergent agitation.

Adult↗
PubMed1998

Inter-rater reliability of the neurological examination in schizophrenia.

Neurological Examination Abnormalities (NEA) are prevalent in schizophrenia, but the significance of this is obscured by methodological problems. The Neurological Evaluation Scale (NES), the most widely used structured neurological examination in schizophrenia research, has had limited study of its inter-rater reliability (IRR). An augmented version of the NES was jointly administered (one examiner-rater and one observer-rater) by three pairs of psychiatrists to two populations of patients with idiopathic psychotic disorders. In addition to the ordinal and categorical data yielded by the original NES, continuous data were recorded in one of the series. Reliability analyses of our populations and a previously published study, reveal consistently adequate IRR in 12 of the 26 items assessed, and inconsistently adequate IRR in an additional 11. Consistent with studies using other NEA schedules, IRR was unacceptably low for some items that rely on subjective severity ratings. Certain rare abnormalities, which posed difficulties for the estimation of IRR, are probably not generally useful in the study of schizophrenia. Reliability estimates of continuous, ordinal and dichotomous data were comparable in most cases. We recommend that certain items from the NES be deleted, and that other studies of NEA in psychiatry follow similar procedures before undertaking further analyses.

Adolescent↗
PubMed1998

Sibling pairs with schizophrenia or schizoaffective disorder: associations of subtypes, symptoms and demographic variables.

BACKGROUND: Affected sibling pairs provide a valuable means of investigating the familial basis of clinical heterogeneity in schizophrenia. METHODS: Associations of schizophrenia subtypes, psychotic symptoms (defined by SAPS/SANS and OPCRIT), affective episodes and demographic variables were studied in 109 sibling pairs with DSM-IV schizophrenia or schizoaffective disorder. RESULTS: None of the subtypes or affective episodes were significantly associated within pairs. A broad definition of positive formal thought disorder, grandiose delusions and delusions of influence (all from OPCRIT) were modestly associated. There was no excess of same-sex pairs. There were modest associations for age of illness onset, pre-morbid adjustment and illness severity. Caution is required in interpreting the results because many statistical tests were carried out. CONCLUSIONS: None of the variables appears to be closely associated with specific genetic or shared environmental factors that contribute liability to schizophrenia. They are at best only weakly associated with such factors, and/or are associated with factors unrelated to the aetiology of schizophrenia.

Adult↗
PubMed1998

Linked polymorphisms upstream of exons 1 and 2 of the human cholecystokinin gene are not associated with schizophrenia or bipolar disorder.

The evidence for a significant genetic contribution to the functional psychoses (schizophrenia and bipolar disorder) is now well established. However, in both cases, the non-mendelian mode of inheritance has made the identification of susceptibility loci particularly challenging. The neuropeptide cholecystokinin (CCK) is present both in the gut and the CNS. Studies of CCK-like immunoreactivity and CCK mRNA levels in human brains have revealed high concentrations in numerous loci and shown colocalisation of CCK with, for example, dopamine and tyrosine hydroxylase. Furthermore, antagonists of CCK-B receptors, which are found most frequently in the brain, inhibit the activity of brain dopamine neurons. Such findings suggest that, with respect to neuropsychiatric disorders, CCK is a suitable candidate for analysis using methods to detect gene variations which have the potential to affect protein structure or expression. In the present study, mutation analyses were carried out on the human CCK gene. Linked polymorphisms were found in the promoter region and in intron 1 close to the 3' mRNA splice acceptor site. However, the allele frequencies of these polymorphisms in samples of individuals affected with either schizophrenia (n=117) or bipolar disorder (n=124) did not differ from those of control subjects (n=234), suggesting that these variations do not confer a predisposition to either of the functional psychoses.

Alleles↗
PubMed1998

Further support for an association between a polymorphic CAG repeat in the hKCa3 gene and schizophrenia.

A recent study has suggested that a polymorphism in the hKCa3 potassium channel may be associated with raised susceptibility to schizophrenia. Despite its modest statistical significance, the study is intriguing for two reasons. First, hKCa3 contains a polymorphic CAG repeat in its coding sequence, with large repeats more common in schizophrenics compared with controls. This is interesting in view of several repeat expansion detection (RED) studies that have reported an excess of large CAG repeats in psychotic probands. Second, the hKCa3 gene is a functional candidate gene because studies of antipsychotic and psychotogenic compounds suggest that glutamatergic systems modulated by SKCa channels may be important in schizophrenia pathogenesis. In the light of the above, we have tested the hypothesis of an association between schizophrenia and the hKCa3 CAG repeat polymorphism using a case control study design. Under the same model of analysis as the earlier study, schizophrenic probands had a higher frequency of alleles with greater than 19 repeats than controls (chi 2 = 2.820, P = 0.047, 1-tail). Our data therefore provide modest support for the hypothesis that polymorphism in the hKCa3 gene may contribute to susceptibility to schizophrenia.

Alleles↗
PubMed1998

The neurologic examination in adult psychiatry: from soft signs to hard science.

Of the proliferating approaches to neuropsychiatric assessment, a relatively neglected technique is the venerable, accessible, noninvasive, and inexpensive neurologic examination. This article organizes and synthesizes the literature on neurological findings in adult psychiatric patients. Problems in conducting and interpreting research in this area are examined, clinically pertinent empirical findings are surveyed, and directions for future investigation are outlined. Most of the "soft signs" can be reliably evaluated, and many have been validated against other techniques. Several psychiatric diagnoses are associated with impaired neurologic performance. Prognosis and treatment selection may also be informed by neurologic findings. The neurologic exam should be regarded as a collection of neurobiologic probes rather than as a single irreducible variable. Future work must better establish interrater and test-retest reliability of individual elements of the neurologic exam in psychiatric populations and focus on developing the clinical utility of individual and combined elements of the neurologic exam.

Adult↗
PubMed1994

Neurological examination abnormalities in neuroleptic-naive patients with first-break schizophrenia: preliminary results.

The authors report preliminary findings from an ongoing prospective study of neuroleptic-naive patients with first-break schizophrenia. They evaluated 17 of these patients and 15 normal subjects with a structured neurological examination before the patients received any medical treatment. The patients with schizophrenia showed significantly greater neurological impairment than did the normal comparison subjects.

Adult↗
PubMed1993

Frontal lobe metabolism and cerebral morphology in schizophrenia: 31P MRS and MRI studies.

The relation between frontal lobe membrane phospholipid metabolism as measured by 31Phosphorus magnetic resonance spectroscopy (31P MRS) and cerebral morphology as measured on magnetic resonance images (MRI) was examined in nine first episode neuroleptic naive schizophrenic patients. Total corpus callosal area was significantly correlated with phosphodiester concentration. When examined separately, this relation was confined to the rostral quartile (genu) of the corpus callosum. The pathophysiological significance of this finding is discussed in relation to neurodevelopmental hypotheses of schizophrenia.

Adult↗
PubMed1991

The value of symptom directed evaluation in the surveillance for recurrence of carcinoma of the breast.

Specific postoperative tests used to diagnose recurrent carcinoma of the breast were evaluated for their ability to have an impact on the over-all course of the disease. Sixty-four patients with recurrent or new contralateral primary disease were divided into two groups based on the method of diagnosis. Those patients with a new complaint at an interval between scheduled follow-up visits and who went on to have tests to document a recurrence were categorized as interval follow-up. Those who were seen at a prearranged regular follow-up period and received tests as recommended by the attending physician or surgeon and had a documented recurrence were classified as routine follow-up. Thirteen patients presented with new contralateral primary disease and 51 with metastatic disease (16, bone; 13, lung; 11, local; three, liver, and eight, multiple). The median time to discovery of recurrence from the primary treatment was 29 and 28 months for the interval and routine groups, respectively. Ninety per cent of the failures occurred by 53 months. The survival time after recurrence was significantly greater in those patients diagnosed routinely (p = 0.003). However, the over-all survival time (from primary therapy to death) was only significantly improved for the routine group when the contralateral new primary diseases were included (p = 0.009). The method of diagnosis of a contralateral primary carcinoma was physical examination and mammogram. Strong recommendations for follow-up testing can be limited to mammogram and physical examination.

Breast Neoplasms↗
PubMed1990

Morphometry of the corpus callosum in monozygotic twins discordant for schizophrenia: a magnetic resonance imaging study.

The corpus callosum (CC) has been the focus of several morphometric studies of patients with schizophrenia, but the results of these studies have been contradictory. In an attempt to improve the reliability of morphometric measurements of the corpus callosum, a computerised image analysis system was used to measure the shape, area, thickness and length of the CC on magnetic resonance imaging (MRI) in 12 pairs of monozygotic twins discordant for schizophrenia (SC). No differences in CC area (anterior, middle, posterior thirds and total), length or vertical thickness of the CC body (at three levels) were demonstrated by t test comparisons of the affected SC and unaffected twins. Statistical analysis of a Fourier expansion series suggested differences in shape between normal and SC cotwins in the second harmonic of the anterior and middle segments and effects of gender on posterior CC shape. These results fail to replicate previous findings of altered length, thickness and area in the schizophrenic CC, but implicate disease-related shape differences in the anterior and middle segment of the corpus callosum and gender-related differences in splenium shape. The disease-related shape distortion suggest ventriculomegaly rather than an intrinsic abnormality of the corpus callosum.

Adult↗
PubMed1989

Axonal counts of the corpus callosum of schizophrenic patients.

This study attempted to identify microscopic correlates to the structural abnormalities reported in the corpus callosum of schizophrenic patients. Sections of the genu, body, and splenium of the corpus callosum were taken from formalin-fixed brains of deceased patients with schizophrenia and nonschizophrenic control subjects. Photomicrographs of stained tissue were projected, and nerve fibers were counted. There were no significant differences (p greater than 0.4) in axonal counts between schizophrenic and control patients for any of the sites sampled. Our results suggest that morphometric abnormalities of the corpus callosum of schizophrenic patients, if present, are not the consequence of a primary process within this structure.

Adult↗
PubMed1983

Interstate migration in Mexico: variations on the Todaro theme.

"This study of migration in Mexico is based upon a modified Todaro approach and utilizes census data in a simultaneous equations model of 13 variables. It is unique in several ways: (a) it introduces proxy variables for employment probability and cost of migration that have not heretofore been found in the literature, but for which data are often available; (b) it illustrates that in some important cases census data have advantages not available through surveys; and (c) it finds that in some sense land reform in Mexico may have operated perversely. Finally, the study opens a new avenue for the study of informal sector growth."

Agriculture↗