Pineal gland calcification and tardive dyskinesia.
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Biomedical subjects
Publications and source records attributed to S R Kay.
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The positive-negative distinction has emerged as a meaningful basis for understanding the heterogeneity of schizophrenia and treatment alternatives, but its delineation requires carefully devised, well validated techniques. This article considers the psychometric requisites for such an instrument and describes 30 criteria associated with operationalization, scale construction, and standardization. Six prominent positive-negative scales are compared on these criteria, and most are found deficient in terms of: a formalized interview procedure; detailed definitions for levels of symptom severity; exclusion of "secondary" negative symptoms; comparative scales to assess positive symptoms, depression, and global severity of illness; broad sampling of negative symptoms; large scale standardization studies; and determination of multiple facets of reliability and validity. The Positive and Negative Syndrome Scale (PANSS) is described as an effort to approach these principles of test standardization, and its clinical and research applications are discussed.
1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) has been shown to produce a parkinsonian syndrome in humans and other primates. Recent studies have demonstrated that in humans the hypothalamus has the highest binding density for (3H) MPTP, which corresponds to monoamine oxidase type B (MAO-B). There is evidence that the conversion of MPTP to the toxic compound MPP+ takes place in the hypothalamus; subsequently, MPP+ is transported to the striatal system, where destruction of nigrostriatal dopamine neurons occurs. Thus, the hypothalamus appears to be a primary target organ of MPTP toxicity. This assumption is supported by the observation that monkeys exposed to MPTP exhibit extensive pathological lesions in the hypothalamus which are manifested clinically by the development of life-threatening anorexia requiring forced feeding to overcome. We discuss the clinical implications of MPTP-induced hypothalamic damage to the pathophysiology of MPTP-induced parkinsonism and to Parkinson disease. It is suggested that consideration of hypothalamic involvement in MPTP-induced parkinsonism may provide a broader understanding of the pathophysiology of parkinsonism and may, in addition, account for the preliminary observations that MAO-B inhibitors retard the progression of Parkinson disease and possibly prolong life expectancy.
Akathisia refers to subjective inner restlessness and a feeling of the need to move. Its occurrence in association with Parkinson disease suggests a common underlying pathophysiological mechanism. We investigated the relationship of neuroleptic-induced akathisia to drug induced parkinsonism in a group of 123 neuroleptic-treated elderly chronic schizophrenic inpatients (mean age: 63.9 +/- 8.9 years). In addition, since neuroleptic-induced akathisia has been noted to be more common in females, we studied the severity of akathisia separately by gender. Akathisia was present in 40 patients (32.5%). We found no significant differences in the severity of akathisia between patients with and these without parkinsonism. Although a significantly larger proportion of females than males had akathisia, there were no significant differences in respect of parkinsonism. Our findings do not support a major role for the dopaminergic system in the pathophysiology of akathisia might be related to dysfunction of nondopaminergic systems.
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Research and treatment of schizophrenia have been impeded by its heterogeneity and the lack of well-standardized methods for a comprehensive assessment of symptoms, including positive and negative dimensions. To study symptom profiles, therefore, we standardized and administered a well-operationalized 30-item psychiatric symptom scale to 240 schizophrenic inpatients. Principal component analysis suggested a pyramidlike triangular model of uncorrelated but nonexclusive syndromes that encompassed the spectrum of psychopathology. Negative, positive, and depressive features constituted divergent points of a triangular base, and excitement made up a separate vertical axis. Paired syndromes could account for symptoms of the paranoid (positive-depressive), disorganized (positive-negative), and catatonic (negative-depressive) diagnostic subtypes. The transversal positions in this model suggested polarized dimensions in schizophrenia, including a prognostic axis (depression-cognitive dysfunction). The findings imply that (1) negative and positive syndromes show factorial validity and distinction from depression but, alone, are insufficient to accommodate the full diversity of symptoms; (2) schizophrenic subtypes derive from a hybrid between unrelated but co-occurring dimensions that may define the fundamental elements of psychopathology; and (3) the pyramidical model is of heuristic value. The results help to clarify the heterogeneity of schizophrenia and to illuminate the path toward syndrome-specific treatments.
This article reviews the cumulative research on positive and negative syndromes in schizophrenia undertaken at the Albert Einstein College of Medicine. A strictly operationalized and standardized syndrome scale was applied in multidimensional, cross-sectional, prospective, longitudinal, phasic, and drug-free studies. The following conclusions about positive and negative syndromes were reached: they can be reliably assessed; they are normally distributed and theoretically independent, thus representing dimensions rather than coexclusive subtypes of schizophrenia; they differ in their association with premorbid functioning, family history of illness, cognitive profile, and neurological signs; their significance appears phase-specific, however, with ominous implications for a negative syndrome found only in the chronic stage; their magnitude is comparably high in all stages of the illness, challenging the view of a progressive negative state; they are stable under drug-free conditions and across months of drug therapy; they both improve with neuroleptics, with marginally better response for positive syndrome; worse long-range outcome is predicted by positive syndrome, especially by disorganized thinking, whereas worse short-term outcome is predicted by both syndromes; the positive-negative distinction, though valid, is incomplete as a model of schizophrenic phenomenology, which must include unrelated depressive and excited components; and Kraepelinian subtypes of schizophrenia seem to comprise not single pathological processes but a hybrid of unrelated, co-occurring syndromes.
It has long been suggested that abnormal functions of the pineal gland may be implicated in the pathophysiology of schizophrenia. We present evidence proposing that diminished melatonin secretion may be associated with the pathophysiology of a subgroup of schizophrenic patients characterized by cerebral atrophy and ventricular enlargement, negative symptoms, impaired cognitive and psychosexual development, onset at pubescence, poor response to neuroleptic medication, and possible increased risk of extrapyramidal symptoms. This view holds that a subnormal plasma melatonin level may be a marker of a subgroup of schizophrenia and may also denote a specific genetic susceptibility.
The purpose of this study was to determine whether schizophrenics with positive, mixed, and negative syndromes are distinguished in terms of visual stimulus registration thresholds and efficiency of information processing. Forty-five schizophrenic inpatients were classified accordingly into groups of 15 each and compared with one another and with 15 normal control subjects on a visual backward masking task. Repeated-measures analysis of variance revealed that all three schizophrenic groups were less efficient information processors than were normal subjects. Relative to the positive group, the negative group displayed significantly longer registration thresholds, fewer correct target stimulus detections, and longer time intervals to achieve their first significant improvement in performance and to first exceed chance response levels. The three syndrome groups were not significantly different in their rates of improvement over trials. Secondary correlational analyses showed that the information-processing measures were unrelated to a variety of demographic, psychiatric, and cognitive developmental variables, although shorter recognition thresholds and shorter unmasking interval scores were associated with faster psychomotor rates. Complex interrelationships were uncovered between the information-processing measures, positive and negative symptomatology, and general psychopathology. The results were interpreted as supporting the validity of the positive-negative distinction for explaining some of the heterogeneity in schizophrenia.
Fifty-one schizophrenic inpatients were divided into two groups, those with and without history of cocaine use, and compared on historical, demographic, cognitive, and psychopathological measures. Patients with a cocaine history were found to be significantly more depressed, less socialized, and more impaired in conceptual encoding and verbal memory, while less disordered in attention. The two groups did not differ in severity of illness or positive and negative syndromes. There were also no differences in control variables such as age, gender, education, intelligence, premorbid adjustment, neuroleptic dose, onset and chronicity of illness, continuity of hospitalization, paranoid subtype, and psychiatric illness in the family. Cocaine history was associated with multiple illicit drug use, but for other substances there was no increased liability for depression or cognitive deficits. The results suggest that the clinical presentation in schizophrenia is significantly associated with prior cocaine experience.
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The positive-negative distinction of schizophrenia has emerged as a valid means of clarifying its heterogeneity. Despite evidence that the two symptom classes may reflect different dimensions of the disease, there is presently no integrated model for understanding of the pathophysiology of these symptoms and their co-occurrence in schizophrenia. We propose that negative phenomena of schizophrenia may be a variant of Parkinsonism. This view is supported by the overlap with Parkinsonism in terms of clinical features, neurochemistry, pharmacology, as well as neuroradiological and neuropathological aspects. As such, negative symptoms may be a manifestation of disease of the basal ganglia and constitute the core pathology in schizophrenia. Positive symptoms, conversely, may reflect an "accessory" process related to a compensatory increase in striatal and limbic dopamine activity following an injury to the dopaminergic system. In the present communication we present a series of studies that support the association of negative schizophrenia and Parkinsonism. Based on this evidence, we suggest that schizophrenic patients with prominent negative symptoms might be managed like patients with Parkinson's disease, namely, with dopaminergic drugs and MAO-B inhibitors. Finally, the association of negative schizophrenia with Parkinsonism raises the possibility that adrenal medullary tissue transplantation, which may benefit a selected group of Parkinsonian patients, may be a future promising therapy for refractory negative schizophrenia.
The Positive and Negative Syndrome Scale (PANSS) consists of a formalized clinical interview and 30 operationally defined items for psychopathology assessment. We report here on the psychometric equivalence of a Spanish language adaptation (PANSS-S), developed to facilitate minority group, multinational, and cross-cultural studies on schizophrenia. Two bilingual psychiatrists simultaneously rated 57 psychiatric inpatients using the PANSS (N = 20), PANSS-S (N = 20), or both methods (N = 17). The PANSS-S demonstrated sound interrater reliabilities (r = .93 for positive and .74 for negative syndrome, p less than .001), which were similar to those from the current PANSS assessment and original standardization studies. In support of criterion-related validity, the means and variance of the two instruments were comparable, and significant cross-correlations were obtained for the principal scales (r = .92 for positive and .83 for negative syndrome, p less than .0001), component symptoms, and five additional psychopathology clusters. The results suggest that the PANSS-S has psychometric properties resembling those of the PANSS and may be used interchangeably in a Spanish-speaking population.
Fundamental questions about the validity and significance of positive and negative syndromes in schizophrenia were addressed by a prospective, double-blind longitudinal study that involved a drug-free placebo baseline, three to four months of neuroleptic treatment, and a three-year poststudy follow-up. From pooled data on 62 schizophrenics, the following findings were observed: (1) a high stability of both syndromes during drug-free conditions; (2) significant correlations of syndrome ratings between the placebo baseline and final neuroleptic week; (3) significant neuroleptic-related improvement in both positive and negative syndromes, with a marginally greater reduction of positive features; (4) independence of the two syndromes during the drug-free baseline but not under neuroleptic conditions; (5) greater symptomatic improvement but more residual disorder portended by both positive and negative syndromes in the drug-free baseline; and (6) poorer functional reconstitution and earlier relapse predicted by a positive syndrome alone. These data supported the validity of the positive-negative distinction in schizophrenia but challenged basic assumptions about its import.
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Because of their severe cognitive and social deficits, seriously impaired and regressed psychotics are often misdiagnosed as mentally retarded. This diagnostic confusion, which carries dire consequences for treatment, has prevailed due to the lack of objective tests directed at this problem. Procedures are needed to specifically measure and differentiate the hallmarks of the intellectual dysfunction in both conditions (i.e., cognitive abnormality [psychosis] and subnormality [mental retardation]). Such methods also must be adapted to the particular problems and limitations of these populations. We propose here the use of three long established tests and a new developmentally rooted Cognitive Diagnostic Battery, one that assesses conceptual, perceptual-motor, and social maturity. Empirical study supported the validity of this Battery for differential diagnosis between mentally and functionally retarded psychotics matched for IQ, 97% of the developmentally disabled group exhibiting deficits on all three tests of conceptual development vs. 27% in the functionally mentally retarded group.
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