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Biomedical subjects

S R Kay

Publications and source records attributed to S R Kay.

At least 19 recordsLinked to original sources
PubMed1992

Multivantaged assessment of depression in schizophrenia.

While it is recognized that depression frequently can occur together with fundamental symptoms of schizophrenia, estimates of the prevalence of schizophrenia-related depression have been very variable. This variability may be due in part to the difficulty in clearly separating depressive symptoms from negative symptoms. A more valid method of assessing depression might combine evaluations from multiple vantage points. This study, which involved 26 hospitalized schizophrenic patients, tested the proposition that complete assessment of depression requires three separate sources of input: self-rating (subjective mood state), clinician rating (affective state), and observer rating (behavioral manifestations). In the present study, patients were evaluated on self-rating instruments for mood states, clinician-rated scales including the Hamilton Rating Scale for Depression, and observer-rated scales. These vantage points, though overlapping in some respects, were found to provide independent information on the experience of depression in schizophrenia. Clinician-rated and observer-rated assessments tended to correlate significantly, while self-rated subjective reports were discordant, thus complementing the assessments from the other two vantage points.

Adult↗
PubMed1992

Abnormal EEG and calcification of the pineal gland in schizophrenia.

Computed tomographic (CT) studies of the brain in schizophrenic patients have demonstrated a variety of structural abnormalities. We reported recently an association between pineal calcification (PC) and cortical and prefrontal cortical atrophy, and third ventricular size on CT scan in chronic schizophrenic patients. These findings indicate that in schizophrenia PC is associated with the morphological brain abnormalities associated with the disease. If PC is, indeed, related to organic cerebral pathology, then one would expect a higher prevalence of pineal gland pathology among patients with electroencephalographic (EEG) abnormalities by comparison to those with a normal EEG. To investigate this hypothesis, we studied the prevalence of PC on CT scan in a sample of 52 neuroleptic-treated schizophrenic patients (29 men, 23 women, mean age: 51.3 years SD = 9.1), of whom 10 (19.2%) had an abnormal EEG. The prevalence of PC in patients with EEG abnormalities was significantly greater by comparison to those with a normal EEG (90.0% vs. 54.8%, X2 = 4.24, p < .05). Since both groups did not differ on any of the historical and demographic data, and since PC was unrelated to neuroleptic exposure, these findings suggest that in schizophrenia PC may be related to the disease process and that it may be a marker of subcortical pathology.

Adult↗
PubMed1992

"Positive" and "negative" movement disorders in schizophrenia.

Investigations aimed at identifying the clinical characteristics that discriminate tardive dyskinesia (TD) from non-TD patients have yielded disparate findings. We have suggested, based on pharmacological and neuroradiological studies, that TD in schizophrenia may be a covariate of positive symptoms while drug-induced parkinsonism (DIP) may relate to negative symptoms. To investigate this hypothesis, we examined in 47 institutionalized schizophrenic patients the relationship of TD and DIP with psychopathology clusters rated on the Positive and Negative Syndrome Scale. We found that involuntary movements of TD were significantly associated with the activation cluster (p < .01), whereas DIP was significantly associated with the anergia cluster (p < .01). These findings thus support the position that TD is a specific facet of the positive syndrome in schizophrenia, while DIP is a specific feature of the negative syndrome. Clinically, the data suggest that schizophrenic patients with predominant positive symptoms may be at increased risk for TD, while those with prominent negative features could be at increased risk for DIP. In analogy with the positive/negative dichotomy, we propose that TD could be regarded as a "positive," while DIP as a "negative" movement disorder.

Adult↗
PubMed1991

The MCPP challenge test in schizophrenia: hormonal and behavioral responses.

In a neuroendocrine challenge paradigm, the present study investigated responses of schizophrenic patients to m-chlorophenylpiperazine (MCPP), a serotonin (5-hydroxytryptamine, 5HT) agonist. In an oral dose of 0.25 mg/kg, MCPP was administered in a placebo-controlled double-blind design to male schizophrenic patients (n = 7) and normal male controls (n = 8). Behavioral (Positive and Negative Syndrome Scale; PANSS) and hormonal (cortisol, prolactin) variables were measured over the subsequent 210 min. The schizophrenic patients experienced an overall exacerbation of psychopathology on MCPP as compared with placebo (p less than 0.05), with specific worsening of PANSS-positive symptoms (p less than 0.025) and PANSS activation (p less than 0.001). In addition, the schizophrenic patients showed significantly lower cortisol (p less than 0.05) and prolactin (p less than 0.05) responses than the normal subjects. The schizophrenic patients had lower peak MCPP blood levels than the normal subjects, although this difference was not statistically significant. The findings are discussed in terms of 5HT receptor(s) sensitivity and the pharmacokinetics of MCPP in schizophrenia.

Adult↗
PubMed1991

The relationship of pineal calcification and melatonin secretion to the pathophysiology of tardive dyskinesia and Tourette's syndrome.

Despite current intensive research, the pathophysiology of tardive dyskinesia (TD), a serious neurological side effect of neuroleptic treatment, is poorly understood. Prompted by the observation of an increased incidence and severity of abnormal perioral movements in neuroleptic-treated pinealectomized, as compared to intact rats, we suggested that the pineal gland exerts a protective effect which mitigates against the development of TD and, by inference, that reduced melatonin secretion may be related to the pathophysiology of TD. To investigate this proposition further, we studied the association of TD with pineal calcification (PC) on CT scan in chronic schizophrenic patients. Our findings revealed a significant association between TD and PC and suggest, furthermore, that PC may be a neuroradiological marker of TD. Since PC may reflect diminished secretory activity of the gland, these findings support the hypothesis that the pathophysiology of TD is linked to disturbances of melatonin secretion. The clinical and therapeutic implications of these novel findings are discussed. In the following communication, in which we introduce the hypothesis that disturbances of 5-HT and melatonin secretion are related to the pathophysiology of TD. Subsequently, we present a series of studies which relate to the association of TD with PC. We conclude by presenting the hypothesis that disturbances in melatonin secretion may also be relevant to the pathophysiology of Tourette's syndrome.

Adult↗
PubMed1991

Neuroradiological covariates of drug-induced parkinsonism and tardive dyskinesia in schizophrenia.

Computed tomographic (CT) studies have demonstrated structural brain abnormalities including cortical atrophy and enlarged lateral ventricles in a subset of schizophrenic patients including those with abnormal involuntary movements. In the following series of studies, we present our findings pertaining to neuroradiological covariates of drug-induced Parkinsonism and Tardive dyskinesia in schizophrenic patients. In these studies we have explored the relationship of Parkinsonism and Tardive dyskinesia to pineal and choroid plexus calcification. In addition, we also investigated the relationship of pineal calcification to schizophrenia, and specifically to the paranoid and nonparanoid subgroups. In a further series of studies, we investigated the neuroradiological covariates of disorders of gait and posture as well as tremor in schizophrenic patients with drug-induced Parkinsonism. In addition, we explored the relationship of Tardive dyskinesia and its subsyndromes to CT scan measurements of cortical and subcortical atrophy in schizophrenia. Our findings highlight the significance of the pineal gland in the pathophysiology of schizophrenia and drug-induced movement disorders. Furthermore, these studies underscore the heterogeneity of Parkinsonism and Tardive dyskinesia.

Adult↗
PubMed1991

Experimental models of schizophrenia.

The Kraepelinian subtypes, developed early in the century, recognize the heterogeneity of schizophrenia but do not reliably predict differences in response to classical neuroleptics. The newer distinction of positive and negative syndromes in schizophrenia carry promise as an approach to identifying meaningful clinical and neurobiological dimensions. The present review summarizes the supportive evidence from a series of investigations using the Positive and Negative Syndrome Scale (PANSS), and a hypothesis on the pathophysiology of negative and positive symptoms is advanced. Our data suggest that: (a) positive and negative syndromes in schizophrenia represent stable, independent dimensions and not co-exclusive subtypes; (b) both are unrelated to the progression of illness; (c) they are differentially related to fundamental aspects of schizophrenia, including premorbid adjustment, cognitive development, family psychiatric history, the cognitive and neuropsychiatric profiles, dopaminergic functions, drug response, and subsequent course; (d) together with depression and excitement, they comprise the fundamental symptomatic components of schizophrenia, which, in their interaction, can account for the specific Kraepelinian subtypes. We have proposed that negative symptoms represent the core pathology in schizophrenia and may be understood as a variant of parkinsonism, hence characterized by dopaminergic deficiency and increased cholinergic activity. This view is supported by the striking overlap with Parkinsonism in regard to clinical features, neurochemistry, pharmacology, neuropathology, and neuroradiology. Positive symptoms are thought to reflect increased dopaminergic activity, which may arise as a compensatory adaptive mechanism to overcome the progressive dopamine loss in the maturing brain. The early onset of schizophrenia by comparison to Parkinson's disease may explain why schizophrenia entails more pronounced positive symptoms, development deficits, and cognitive, social, and emotional impairments. We describe evidence that pineal calcification, which may reflect disturbance of melatonin functions, appears to be a nongenetic factor in schizophrenia associated with perinatal injury. This may in part underlie the negative syndrome and its response to antipsychotic compounds with serotonergic (5-HT) antagonism.

Humans↗
PubMed1991

Neuroradiological facets of cognitive abnormality in schizophrenia.

Cognitive abnormality has long been regarded as a core feature of schizophrenia, but its nature and etiopathology have been poorly understood. Predicated on new tests that characterize fundamental cognitive impairments, we investigated their relationship to four neuroradiological markers that have been previously implicated in schizophrenia: choroid plexus calcification, cerebellar atrophy, third ventricle enlargement, and pineal calcification. Twenty-three chronic schizophrenic inpatients meeting RDC and DSM-III diagnostic criteria were stabilized on chlorpromazine and assessed independently on a cognitive battery and on CT scan. The results indicated that all four neuroradiological variables were independent of one another and of demographic, historical, and general intellectual measures. The neuroradiological assessments, however, correlated significantly with different cognitive parameters, implying separate pathophysiological bases for distinct profiles of cognitive abnormality. The findings support a "dual-process model" of cognitive dysfunction that posits developmental and arousal-related components which may, more generally, underlie the positive-negative dimension of schizophrenia.

Adult↗
PubMed1991

Risk factors for neuroleptic-induced movement disorders.

Chronic neuroleptic therapy may be associated with the development of diverse movement disorders including Tardive dyskinesia (TD), Parkinsonism, dystonia, and akathisia in a subset of schizophrenic patients. It is presently unknown why only a proportion of neuroleptic-treated patients develop these movement disorders. In the following communication, we present a series of studies which demonstrate that the development of these movement disorders may be facilitated by certain risk factors including disturbances in pineal melatonin functions, diabetes mellitus, cognitive deficits, suicidal behavior, and disturbances in the functions of the choroid plexus. Recognition of these biological factors may prove useful in: (a) further understanding of the pathophysiology of these disorders, and (b) identifying patients at risk for these movement disorders.

Antipsychotic Agents↗
PubMed1991

The relationship of pineal calcification to cortical atrophy in schizophrenia.

Several recent computed tomographic (CT) studies have provided evidence for structural cerebral abnormalities in schizophrenia. CT scan findings included enlargement of the lateral cerebral ventricles, cortical atrophy, third ventricular dilatation, ventricular asymmetry, and cerebellar atrophy. In addition, there is increasing data to suggest that abnormal pineal melatonin functions are associated with the pathophysiology of schizophrenia. To explore further the relationship of the pineal gland to the pathophysiology of schizophrenia and its specific association with structural abnormalities, we investigated: (a) the relationship of pineal calcification (PC) to computerized tomographic (CT) scan measurements of cortical and subcortical atrophy in 41 chronic schizophrenic patients, and (b) the relationship of PC size to CT scan measurements and cortical and subcortical atrophy in 51 chronic schizophrenic patients. Results of the first study revealed that the presence of PC was significantly associated with measurements of prefrontal cortical atrophy (p less than .01), while there was no association with measurements of parieto-occipital atrophy, sulcal prominence, or ventricular brain ratio (VBR). These findings support the notion that the various structural brain abnormalities in schizophrenia may reflect different pathological processes and that abnormal pineal melatonin functions may be associated with the pathophysiology of prefrontal cortical atrophy. In addition, since some clinical facets of schizophrenia covary with frontal lobe dysfunction, our findings highlight the significance of abnormal pineal functions for the pathophysiology of schizophrenia. In the second study we found a significantly higher prevalence of pathologically enlarged PC (i.e., greater than 1 cm in diameter) in schizophrenia as compared to controls of similar age. In addition, we found a significant association between CT scan measurements of cortical atrophy and pathologically enlarged PC size (p less than .05). By contrast, PC size was unrelated to VBR. These findings demonstrate a specific association between pathologically enlarged PC and cortical atrophy in schizophrenia. The implications of these findings to the pathophysiology of schizophrenia and, specifically, to the morphological abnormalities that accompany the disease are discussed.

Adult↗
PubMed1991

Atrophy of the cerebellar vermis: relevance to the symptoms of schizophrenia.

Degeneration of the cerebellar vermis is a common pathological and neuroradiological feature of chronic schizophrenia, but its relationship to symptoms of the disease are poorly understood. We investigated the relationship of vermal cerebellar atrophy on CT scan to features of positive (productive) and negative (defect) dimensions of schizophrenia as well as to symptoms of general psychopathology in a sample of 23 chronic schizophrenic patients. For comparison, we also studied the relationship of third ventricular width (TVW), which reflects periventricular and diencephalic atrophy, to these features of schizophrenic symptomatology. Vermal cerebellar atrophy was found in 43.5% of patients and correlated significantly with general psychopathology and, more specifically, with feelings of guilt and disturbance of volition. It was unrelated to global positive or negative features of schizophrenia. By contrast, TVW was uniquely associated with global negative syndrome. These observations indicate that degeneration of the cerebellar vermis and enlargement of the third ventricle are integral aspects of schizophrenia, and that each contributes independently to specific clinical aspects of the disease.

Atrophy↗
PubMed1991

Tobacco addiction as a marker of age at onset of schizophrenia.

Schizophrenia is a heterogenous disorder, with diversity in symptoms, course, prognosis, and probably etiology. The timing of its onset (i.e., early vs. late) not only predicts outcome of illness, but also corresponds to fundamental neurochemical and neuroendocrine distinctions. There is recent evidence that early age at onset of schizophrenia is associated with more prominent negative symptoms, which are associated with decreased dopaminergic functions in the limbic system. Since addictive behaviour may be related to decreased dopamine activity in the mesolimbic reward circuitry, we predict a higher prevalence of tobacco addiction in patients with an earlier age at onset of schizophrenia. To investigate this hypothesis, we studied the association of cigarette smoking to age at onset of illness in a sample of 142 chronic schizophrenic inpatients, 73 of whom were smokers. We found that patients who smoked had a significantly earlier age at onset of psychiatric illness as compared to the nonsmokers (p less than .01). Since damage to dopaminergic systems at the lateral hypothalamic level of the medial forebrain bundle and in the ventral tegmental reward system produces the strongest indication of reward, our data suggest that alterations in dopaminergic functions in these systems may be linked to the timing of onset of schizophrenic symptoms.

Aged↗
PubMed1990

Neurological signs and the positive-negative dimension in schizophrenia.

Schizophrenic patients have been observed to manifest a variety of abnormal neurological signs, but the nature of their association with differing clinical presentations is less well established. To address this issue, we administered a newly compiled neurological inventory to 28 well-characterized chronic schizophrenic inpatients and separately assessed them on the Positive and Negative Syndrome Scale and on control variables that included measures of global pathology, chronicity of illness, neuropsychological and intellectual integrity, and extrapyramidal dysfunction. We found, first, that our neurological battery provided statistically independent measures of apraxia, fine motor function, and prefrontal, parietal, and nonlocalizing signs. A significant association emerged between negative symptomatology and neurological signs of prefrontal impairment (p less than 0.01), which could not be accounted for by any of the control variables. Positive symptoms were associated with an absence of parietal and nonlocalizing signs; however, these correlations were mediated by higher neuroleptic doses in these patients. There was no association between any neurological sign and age, extrapyramidal symptoms, general neuropsychological integrity, education, IQ, or severity or chronicity of illness. We concluded that the negative syndrome in schizophrenia represents a distinct dimension of psychopathology that is related specifically to prefrontal deficit.

Adult↗