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C A Kaufmann

Publications and source records attributed to C A Kaufmann.

At least 37 records · Page 2Linked to original sources
PubMed1994

Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative.

This article reports on the development and reliability of the Diagnostic Interview for Genetic Studies (DIGS), a clinical interview especially constructed for the assessment of major mood and psychotic disorders and their spectrum conditions. The DIGS, which was developed and piloted as a collaborative effort of investigators from sites in the National Institute of Mental Health (NIMH) Genetics Initiative, has the following additional features: (1) polydiagnostic capacity; (2) a detailed assessment of the course of the illness, chronology of psychotic and mood syndromes, and comorbidity; (3) additional phenomenologic assessments of symptoms; and (4) algorithmic scoring capability. The DIGS is designed to be employed by interviewers who exercise significant clinical judgment and who summarize information in narrative form as well as in ratings. A two-phase test-retest (within-site, between-site) reliability study was carried out for DSM-III-R criteria-based major depression, bipolar disorder, schizophrenia, and schizoaffective disorder. Reliabilities using algorithms were excellent (0.73 to 0.95), except for schizoaffective disorder, for which disagreement on estimates of duration of mood syndromes relative to psychosis reduced reliability. A final best-estimate process using medical records and information from relatives as well as algorithmic diagnoses is expected to be more reliable in making these distinctions. The DIGS should be useful as part of archival data gathering for genetic studies of major affective disorders, schizophrenia, and related conditions.

Adult↗
PubMed1994

Effects of pharmacologic catecholamine manipulation on smooth pursuit eye movements in normals.

The pathophysiology of schizophrenia may be related directly or indirectly to abnormal dopaminergic activity. Both subcortical excess and frontal cortical deficiency of dopamine have been suggested, and primary or downstream failures of dopamine activation to the prefrontal cortex has been posited to explain some of the cognitive deficiencies in schizophrenia patients. Although the prefrontal cortex may also be a site for the disruption of smooth pursuit eye movements (SPEM), the most substantially described psychophysiological marker for schizophrenia vulnerability, no relationship of SPEM to dopaminergic activity has been demonstrated. In this study we explored the effect of altered dopamine function on SPEM quality through pharmacological manipulation of catecholamine tone in 11 healthy subjects. The subjects had SPEM measured at baseline, and under challenge conditions including amphetamine (0.3 mg/kg), haloperidol (2 mg), placebo, and combined amphetamine with haloperidol. Changes in the profile of mood scale (POMS) confirmed the expected subjective central nervous system effects the agents. Placebo and amphetamine had no effect on qualitative ratings of SPEM, but haloperidol, alone and in combination with amphetamine, disrupted eye tracking, producing a pattern of small saccadic intrusions characteristic of patients with schizophrenia. These findings link dopaminergic blockade with SPEM disruption in normal subjects.

Adult↗
PubMed1994

Prenatal nutritional deprivation as a risk factor in schizophrenia: preclinical evidence.

We will review evidence from preclinical literature that prenatal nutritional deprivation produces neurochemical, morphological, and electrophysiological effects reminiscent of those seen in clinical studies of schizophrenia. We will focus on effects of nutritional deficiency that are likely to have implications for schizophrenia. These include disruption of neurotransmitter systems such as dopamine and serotonin and dysgenesis of the hippocampal formation. Preclinical studies show enhanced release and turnover of dopamine and serotonin following prenatal and early postnatal nutritional deficiency. Morphology of the hippocampus, as well as electrophysiology and hippocampally-mediated behaviors are also altered. Although intriguing, these studies have not been conducted with schizophrenia in mind, and thus, outcome measures that may be more specifically related to schizophrenia have not been examined. We propose that further preclinical studies that examine the consequences of prenatal nutritional deficiency, which may lead to altered neuronal migration and other developmental abnormalities, may be useful in understanding the etiology of schizophrenia.

Animals↗
PubMed1994

Minor physical anomalies in schizophrenia.

Using the Waldrop scale, minor physical anomalies were studied in 82 Caucasian subjects, including 41 schizophrenic and 8 bipolar adults, as well as 14 normal and 19 mentally retarded adults. An increased incidence of minor physical anomalies was found in the mentally retarded adults relative to the other groups. Consistent with previous studies, there was a trend for the total mean Waldrop score of the schizophrenic group to be higher than the mean score of the normal group. Minor physical anomalies (assessed by the Waldrop scale), however, appear to be of questionable utility in identifying "congenital" schizophrenia, at least as this putative subgroup of schizophrenia is currently conceptualized.

Adolescent↗
PubMed1994

Odor discrimination deficits in schizophrenia: association with eye movement dysfunction.

Odor discrimination deficits were found in 80% of 20 schizophrenia patients and in none of the 20 age- and sex-matched comparison subjects. Olfactory discrimination was reliably measured in the patients. Twelve patients in this study also had smooth pursuit eye movement (SPEM) qualitatively recorded. The olfactory discrimination scores were highly correlated to SPEM but not to other clinical measures. This correlation suggests a shared neurobiology, possibly involving working memory.

Adult↗
PubMed1992

Clathrin light chain B: gene structure and neuron-specific splicing.

The clathrin light chains are components of clathrin coated vesicles, structural constituents involved in endocytosis and membrane recycling. The clathrin light chain B (LCB) gene encodes two isoforms, termed LCB2 and LCB3, via an alternative RNA splicing mechanism. We have determined the structure of the rat clathrin light chain B gene. The gene consists of six exons that extend over 11.9 kb. The first four exons and the last exon are common to the LCB2 and LCB3 isoforms. The fifth exon, termed EN, is included in the mRNA in brain, giving rise to the brain specific form LCB2 but is excluded in other tissues, generating the LCB3 isoform. Primary rat neuronal cell cultures express predominantly the brain specific LCB2 isoform, whereas primary rat cultures of glia express only the LCB3 isoform, suggesting that expression of the brain-specific LCB2 form is limited to neurons. Further evidence for neuronal localization of the LCB2 form is provided using a teratocarcinoma cell line, P19, which can be induced by retinoic acid to express a neuronal phenotype, concomitant with the induction of the LCB2 form. In order to determine the sequences involved in alternative splice site selection, we constructed a minigene containing the alternative spliced exon EN and its flanking intron and exon sequences. This minigene reflects the splicing pattern of the endogenous gene upon transfection in HeLa cell and primary neuronal cell cultures, indicating that this region of the LCB gene contains all the necessary information for neuron-specific splicing.

Alternative Splicing↗
PubMed1992

Characterization of a synaptic antigen of interest in neuropsychiatric illness.

Monoclonal antibodies exhibiting relative differences in binding to brain homogenates from diseased versus control brains may be useful probes into the molecular pathology of neuropsychiatric illness. To be of value, the antibodies must be useful in characterization of the antigens putatively involved in the illness. An antibody called EP10 showed some differences in binding to homogenates from a small sample of schizophrenia brains compared with controls. In the present study, the antigen for this antibody was characterized in control brains using quantitative, immunocytochemical, and biochemical techniques. The antigen is a 38,000 dalton synaptic vesicle protein, which is identical to synaptophysin by immunological criteria. However, the EP10 epitope is of interest, as this binding site does not appear to be present in rat or bovine synaptophysin. Brain regional studies using EP10 indicate that the antigen may be present in only a subset of synaptic terminals. Further studies are required to fully characterize the epitope, and to determine the significance of the earlier findings related to schizophrenia.

Animals↗
PubMed1992

Blood-CSF barrier permeability and central nervous system immunoglobulin G in schizophrenia.

The ratio of albumin in cerebrospinal fluid (CSF) to serum may serve as an index of the integrity of the blood-CSF barrier, with increases in this ratio indicating increased permeability. The ratio of immunoglobulin G (IgG) in CSF to serum (divided by the albumin ratio to correct for variance in blood-CSF permeability) represents an index of the endogenous production of IgG in the central nervous system (CNS), with increases reflecting a possible infectious and/or autoimmune process stimulating central IgG synthesis. We analyzed simultaneously collected CSF and serum samples from 46 schizophrenic subjects, 8 of whom were studied both on and off neuroleptic treatment, and samples from 20 normal controls. The data indicated increases in CSF/serum albumin ratios or CSF/serum IgG indices in 22% and 20%, respectively, of the schizophrenic patients. Only 3 patients showed elevations in both indices. Comparison of values on and off neuroleptics indicated no significant effect of neuroleptics on these indices.

Adolescent↗
PubMed1992

Association of schizophrenia and partial trisomy of chromosome 5p. A case report.

A normal balanced chromosome 5 translocation carrier (5:14) (p14.1; q32.3) produced one offspring with a 5p deletion syndrome (cri du chat syndrome) and two with a partial trisomy (one with schizophrenia and the other with refractory epilepsy). We had hypothesized that the translocation might be complex and involve 5q, overlapping with a schizophrenia associated area described by Bassett et al., (1988). Cytogenetic study, however, indicated that there was no overlap in the involved chromosome 5 trisomy for this individual with schizophrenia and the trisomic region previously described. The probands with the trisomy and the cytogenetic findings are described in this report. Alternative interpretations are suggested to explain the association of schizophrenia and chromosomal abnormalities.

Adolescent↗
PubMed1989

Monoclonal antibodies to study the brain in schizophrenia.

Twelve monoclonal antibodies were developed which show selective reactivity with brain tissue homogenates from 4 patients with schizophrenia compared to 4 normal controls. Certain antibodies were more reactive with tissue from cases with schizophrenia, others with control tissue. Patterns of reactivity also depended on brain region tested. Differences in reactivity generally ranged from 2- to as much as 8-fold. This panel of monoclonal antibodies may be useful to investigate the pathophysiology of schizophrenia.

Adult↗
PubMed1989

Deletion mapping of DNA markers to a region of chromosome 5 that cosegregates with schizophrenia.

Two independent lines of evidence support the localization of a schizophrenia susceptibility locus to the proximal long arm of chromosome 5. A partial trisomy of chromosome 5 (5q11.2-q13.3) cosegregates with the disorder in a Canadian family of Chinese descent, and DNA markers from proximal 5q cosegregate with schizophrenia (plus related disorders) in families of British and Icelandic descent. We constructed a human:hamster hybrid cell line (HHW 1064) whose only human complement is a chromosome 5 that is missing the trisomic region associated with schizophrenia. In combination with a "matched" cell hybrid (HHW 105) containing an intact chromosome 5, we physically mapped DNA markers relative to the trisomy. "Schizophrenia-linked" DNA markers p105-153Ra (D5S39) and p105-599Ha (D5S76) map within the trisomy and proximal to the 5q11.2 breakpoint, respectively. The hybrid cell lines HHW 105 and HHW 1064 together provide a means to identify and generate syntenic DNA markers to further investigate the location of a schizophrenia locus.

Animals↗
PubMed1989

Physical mapping, linkage analysis of a putative schizophrenia locus on chromosome 5q.

Two recent studies have suggested that a schizophrenia susceptibility locus may lie on the proximal long arm of chromosome 5. Partial trisomy of a 20-30 centimorgan region of chromosome 5 (5q11.2-13.3) was found to cosegregate with schizophrenia in a Canadian family of Chinese descent. Moreover, DNA markers from proximal 5q (D5S39, D5S76) were found to be linked to schizophrenia and related disorders in seven British and Icelandic families. We now report an initial physical map of DNA markers relative to the partial trisomy chromosome 5, as well as preliminary evidence against linkage of this region to schizophrenia in four American families.

Chromosome Mapping↗
PubMed1989

Genetics and psychiatry: past discoveries, current dilemmas, and future directions.

Family, twin, and adoption studies have suggested an important role for hereditary factors in the etiology and pathogenesis of several psychiatric disorders. Advances in molecular and statistical genetics may very well reveal the identity of these factors, which may include single genes. Linked markers, critical to the discovery of abnormal genes in several medical conditions, have been reported for Huntington's disease, Alzheimer's disease, bipolar disorder, and schizophrenia. Psychiatric disorders pose particular problems (etiologic heterogeneity, incomplete penetrance, variable expressivity) for genetic research. New practical and ethical questions also arise. Nevertheless, knowledge may emerge that will suggest new approaches to diagnosis, prevention, and treatment.

Diseases in Twins↗
PubMed1988

Intracerebral inoculation of experimental animals with brain tissue from patients with schizophrenia. Failure to observe consistent or specific behavioral and neuropathological effects.

To test the possibility that some cases of schizophrenia result from infection with a transmissible slow viral agent, 57 experimental animals (six chimpanzees, 12 Old World monkeys, 17 New World monkeys, and 22 guinea pigs) were inoculated intracerebrally with brain tissue from ten patients and followed up for six years. Behavioral comparisons with control animals revealed no consistent behavioral differences. Histological, immunohistochemical, and morphometric examination of brains of animals that died revealed no specific neuropathological abnormalities. These findings do not support a role for a virus-induced slow infection in the pathogenesis of schizophrenia but must be weighed against methodological limitations in animal susceptibility, disease communicability, and assay sensitivity.

Adult↗
PubMed1987

Cerebrospinal fluid amino acid concentrations in chronic schizophrenia.

The concentrations of the excitatory amino acid, glutamate, the inhibitory amino acids, glycine and taurine, and the inactive amino acids, glutamine and alanine, were determined in cerebrospinal fluid samples from 12 neurological control and 17 chronic schizophrenic patients. No significant differences were observed in any amino acid between the study groups. Within the schizophrenic group, no differences were observed between paranoid and undifferentiated patients. The concentrations of these amino acids in samples obtained from six schizophrenic patients during drug-free as compared to haloperidol-treatment periods also did not differ. These results do not support the glutamate hypothesis of schizophrenia.

Adult↗