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W T Carpenter

Publications and source records attributed to W T Carpenter.

At least 73 records · Page 4Linked to original sources
PubMed1993

Diagnosis and classification of schizophrenia.

Schizophrenia is a clinical syndrome of both extraordinary importance and extraordinary complexity. Its conceptual history contains many perspectives on the "essential" nature of the illness. For example, Kraepelin in 1919 emphasized primarily onset and course, although he also stressed the importance of some symptoms such as changes in affect and volition. Bleuler in 1911 took a more cross-sectional approach and attempted to identify fundamental characteristic symptoms, especially stressing fragmenting of thought processes. Schneider's (1959) approach was cross-sectional, stressing a group of "first-rank symptoms." DSM-III and its successors attempted to achieve a synthesis of these concepts. Nevertheless, heterogeneity in the clinical presentation of schizophrenia is certain, and heterogeneity in pathophysiology and etiology is likely. Although we can now define a particular construct of schizophrenia with reasonable agreement, the construct must be recognized as provisional and based on a need to achieve consensus about definitions rather than on an understanding of pathophysiology and etiology. The major challenge confronting the student of schizophrenia is to identify its mechanisms and causes in order to develop improved strategies for treatment and prevention. Several different approaches have been proposed to achieve this goal. Early attempts to explore and validate the construct of schizophrenia stressed descriptive and epidemiological techniques; the "validity" of a given construct of schizophrenia would be determined by evaluation of familial aggregation, course and outcome, response to treatment, and laboratory tests. This earlier approach to validation is now complemented by one that draws on techniques from neuroscience and attempts to understand schizophrenia in terms of underlying neural mechanisms. While the earlier approach conceptualized schizophrenia primarily in terms of a single disease entity, the second approach is particularly useful for the exploration of subtypes or dimensions. Research strategies for the study of schizophrenia have been developed to explore its heterogeneity. Three different competing models are discussed: (1) A single etiopathological process leading to diverse manifestations, similar to multiple sclerosis; (2) multiple disease entities leading to schizophrenia by different etiopathological processes, similar to the syndrome of mental retardation; and (3) specific symptom clusters within schizophrenia reflecting different disease processes that come together in different ways in different patients. Each of these models has strengths and weaknesses for the identification of etiology and pathophysiology.

Humans↗
PubMed1993

Structural abnormalities in deficit and nondeficit schizophrenia.

OBJECTIVE: Previous studies have suggested the involvement of the frontal and parietal cortices and thalamus in a neural circuit underlying the production of primary enduring negative or deficit symptoms of schizophrenia. The purpose of this study was to examine whether structural changes in the proposed circuit are associated with the production of deficit symptoms. METHOD: Magnetic resonance imaging was used to measure the volume of selected circuit brain regions (i.e., the prefrontal region and caudate) and noncircuit brain regions (i.e., the amygdala/hippocampus complex) in 17 deficit and 24 nondeficit schizophrenic outpatients and 30 normal comparison subjects. RESULTS: Right and left total prefrontal volumes discriminated deficit from nondeficit patients, with prefrontal volumes being smaller in nondeficit patients. There were no differences between the two schizophrenic subgroups in left caudate or right and left amygdala/hippocampus complex volumes. The right caudate was larger in deficit patients, but the difference between the two schizophrenic subgroups was not significant. There were no differences between deficit and normal subjects on any prefrontal region measure. Nondeficit patients had smaller total right and left prefrontal volumes than normal subjects. Both schizophrenic subgroups had larger left caudate volumes and smaller right and left amygdala/hippocampus complex volumes than the normal subjects. There was a trend for deficit patients to have larger right caudate volumes. CONCLUSIONS: These results suggest that structural changes in the prefrontal region are not responsible for deficit symptoms. The caudate, particularly the right caudate, may be associated with the production of these symptoms.

Frontal Lobe↗
PubMed1993

Clozapine treatment of outpatients with schizophrenia: outcome and long-term response patterns.

OBJECTIVE: The purpose of the study was to examine the effects of clozapine in treating moderately ill schizophrenic outpatients and to determine the length of medication trial needed to identify responders and nonresponders. METHODS: Rates of clinical responses, relapses and hospitalizations, and levels of symptomatology and functioning were assessed for 30 chronic schizophrenic outpatients who received clozapine for one year. For some patients, data on relapse and hospitalization during treatment were compared with data from the year before treatment. RESULTS: Eighteen of the 30 patients met criteria for sustained response; 17 of the responders were identified within the first four months of treatment. Patients experienced significantly fewer relapses and hospitalizations during treatment than in the previous year. Improvement in positive symptoms, general symptomatology, and levels of functioning reached a plateau during the first six months of treatment and remained at that level during the second six months. Negative symptoms and quality of life showed nonsignificant improvements at 12 months. CONCLUSIONS: Results support the use of clozapine in treating chronic, residually symptomatic schizophrenic outpatients. A four-month clozapine trial may be adequate to detect clinical responders in this population.

Adult↗
PubMed1992

Plasma prolactin as a predictor of relapse in drug-free schizophrenic outpatients.

A low plasma prolactin concentration has been reported to be associated with an increased risk of subsequent relapse in patients with schizophrenia. Prolactin concentration was measured in samples from stable schizophrenic men who were outpatients just prior to neuroleptic withdrawal. No relationship between prolactin concentration and time to subsequent relapse was found. Prolactin concentration may predict time to relapse only in populations characterized by specific demographic features or medication history.

Administration, Oral↗
PubMed1992

Clinical predictors of relapse following neuroleptic withdrawal.

The validity of previously hypothesized predictors of elapse following neuroleptic discontinuation was examined. One hundred sixty-two outpatients, with either Research Diagnostic Criteria schizophrenia or schizoaffective disorder, were discontinued from neuroleptic medication for a 28-day period or until judged to be relapsed. Pre-discontinuation neuroleptic dosage level, the severity of psychotic symptoms, and the presence of dyskinetic movements prior to neuroleptic discontinuation were the predictor variables. Of the 162 patients, 62.7% did not relapse during the study period. There were no differences in the survival rates between the patients withdrawn from oral versus depot neuroleptics. Neuroleptic dosage, but not severity of psychotic symptoms or dyskinetic movements, predicted relapse. These results support the hypothesis that pre-withdrawal neuroleptic dosage level predicts relapse, but fail to validate either severity of psychotic symptoms or presence of dyskinetic movements as predictors of relapse.

Administration, Oral↗
PubMed1992

Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome.

A hypothesis of psychosis localization in schizophrenia was derived from studying metabolic alterations in rat brain in response to phencyclidine hydrochloride administration. Since phencyclidine and its selective agonist dizocilpine maleate (MK801) induced overlapping and long-lasting metabolic alterations predominantly in limbic areas, the hypothesis developed that schizophrenic patients with psychosis would evidence functional abnormalities in limbic circuits compared with normal controls. Accordingly, 12 actively psychotic, drug-free patients with schizophrenia and matched normal controls underwent functional brain scans using positron emission tomography and fluorodeoxyglucose. Regions of interest were identified on five matched axial slices in each patient and control subject, and average metabolic rates were calculated. Patients with schizophrenia showed a significantly lower regional cerebral metabolic rate of glucose in the hippocampus and the anterior cingulate cortex than did normal controls, but not in neocortical areas or in the extrapyramidal system. When the group of schizophrenic patients was divided into deficit and nondeficit types, a preliminary exploratory analysis suggested thalamic, frontal, and parietal cortical hypometabolism in the deficit subgroup, with normal metabolism in the nondeficit patient group in those areas; in contrast, hippocampal and anterior cingulate cortical metabolism was reduced in both deficit and nondeficit subtypes. These results suggest that the limbic system, especially the hippocampus, is functionally involved in schizophrenic psychosis and that different manifestations of schizophrenia may involve different neuronal circuits.

Adolescent↗
PubMed1992

Risk factors in schizophrenia. Season of birth, gender, and familial risk.

The risk for schizophrenia among first-degree relatives of schizophrenic probands obtained from an epidemiological sample using family history methods was examined to determine whether month of birth of the proband was associated with familial risk. The results of this study of the first-degree relatives of 106 female schizophrenics and 275 male schizophrenics suggested that the relatives of probands born in the months February to May had the highest risk, although the association between month of birth and familial risk among the male probands was present only for those relatives who had onset of schizophrenia before the age of 30.

Adult↗
PubMed1991

Carbamazepine maintenance treatment in outpatient schizophrenics.

A double-blind crossover trial was used to evaluate carbamazepine as the sole maintenance treatment of chronic, nonmanic schizophrenic outpatients whose conditions had been stabilized with the use of neuroleptics prior to study. Criteria of treatment effectiveness included the number of patients relapsing and time to relapse over a 95-day neuroleptic-free period during which either carbamazepine or placebo was administered. Relapse was determined by the concordance of psychiatric ratings and independent clinical judgements indicating significant worsening. Results for 27 patients (13 receiving carbamazepine and 14 receiving placebo) involved in the first phase of this treatment comparison were nondifferentiating. Corroborating descriptive findings in the second phase were available for 14 of these patients. There was no evidence supporting the existence of a treatment-relevant subgroup defined by episodic dyscontrol phenomena.

Adult↗
PubMed1991

The prediction of outcome in schizophrenia. IV: Eleven-year follow-up of the Washington IPSS cohort.

Two- and five-year follow-up observations of the International Pilot Study of Schizophrenia's Washington cohort provided data bearing on several controversial issues regarding the course of schizophrenia. Forty schizophrenic patients have now been observed 11 years after their index admission. Social, occupational, hospital utilization, and symptom areas of functioning continue to be only modestly correlated with one another and do not become increasingly uniform over time. Initial prognostic variables continue to be more predictive of long-term outcome than are cross-sectional symptom manifestations. Restricted affect at the initial evaluation had been a predictor of 5-year outcome, but it was not a significant predictor of outcome at 11 years. While serious long-term consequences of illness are observed, the follow-up data suggest that the illness tends to reach a plateau of psychopathology early in the course, with as many patients tending to improve in the long-term as those who tend to show further deterioration.

Adolescent↗
PubMed1990

Immunopathology and viral reactivation. A general theory of schizophrenia.

A theory is proposed that explains a broad range of clinical manifestations in schizophrenia. It is a heuristic device for organizing research in the neuroimmunology and virology of schizophrenia. This approach is different from other immune and viral theories of schizophrenia and defines testable hypotheses for further theory refinement or rejection. Defective alpha-interferon (aIFN) regulation resulting in excessive effect is postulated to cause schizophrenia. The role of aIFN in the regulation of development and its induction within the brain by the reactivation of viruses that are commonly present in the normal central nervous system (CNS) are the primary pathophysiological mechanisms. Biological properties of aIFN include neural excitation, opiate and adrenocorticotropic hormone activity, and inhibition of cellular proliferation and differentiation. Psychosis results from in situ viral stimulation of aIFN production in the CNS of a vulnerable host having defective regulation of either sensitivity or production. Negative symptoms result from aIFN effects on CNS development and the behavioral toxicity of aIFN. Biological developmental abnormalities, gender differences in severity, and decline in psychotic symptoms with age are discussed in the context of the theory. Research strategies and specific testable hypotheses are presented.

Adult↗
PubMed1990

Schizophrenia: age at onset, gender and familial risk.

In a family history study of 366 schizophrenic probands and their 1851 first-degree relatives, we found a relationship between age at onset of psychosis in the male probands and the risk for schizophrenia in their relatives. The relatives of male schizophrenic probands whose onset of psychosis occurred when they were younger than 17 years of age had an increased risk of schizophrenia when compared with the relatives of male probands with an age at onset greater than 17. We did not find an association between age at onset of psychosis in the female probands and familial risk. Cox proportional hazards models permitted us to examine the relationship between age at onset of psychosis in the probands and familial risk while controlling for possible confounding effects.

Adolescent↗
PubMed1990

Clinical correlates of the deficit syndrome of schizophrenia.

The authors propose using primary and enduring negative or deficit symptoms for dichotomizing schizophrenic patients into two groups, deficit and nondeficit. The validity of this approach was examined by comparing 17 deficit and 17 nondeficit patients for differences in premorbid adjustment and degree of neurological impairment. Deficit patients were characterized by poorer premorbid adjustment and greater neurological impairment. Neurological impairment was not related to premorbid adjustment in either group or in the total patient population. These findings support the utility of deficit symptoms for defining a more homogeneous subgroup of schizophrenia.

Adult↗