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Biomedical subjects

J A Lieberman

Publications and source records attributed to J A Lieberman.

At least 163 records · Page 9Linked to original sources
PubMed1992

Volumes of ventricular system subdivisions measured from magnetic resonance images in first-episode schizophrenic patients.

In vivo brain imaging and postmortem investigations have demonstrated structural anomalies in the brains of schizophrenic patients. However, previous studies have not established clear relationships between the characteristic symptoms of the disorder and neuropathologic changes in specific brain regions. We have obtained high-resolution magnetic resonance brain images of first-episode schizophrenic and normal control subjects and, with a computerized mensuration system, determined the volumes of the different components of the entire ventricular system. Volumes of ventricular segments were significantly larger in patients than controls (differences ranged from 17% to 40%). Temporal horn enlargement consistently demonstrated significant correlations with a broad range of schizophrenic symptoms. Our data indicate that anomalies of limbic structures in the medial temporal lobe surrounding the temporal horn play a crucial pathophysiologic role in schizophrenia.

Adolescent↗
PubMed1992

Clinical profile of clozapine: adverse reactions and agranulocytosis.

The arrival of clozapine has been one of the most significant developments in antipsychotic drug treatment since the advent of chlorpromazine ushered in the psychopharmacologic era. However, its utilization has been significantly limited and complicated by its potential to cause adverse effects and agranulocytosis in particular. It must be emphasized that clozapine has a side effect profile that is in many ways distinct from standard typical antipsychotic drugs. Side effects with clozapine are common and range from the benign to the potentially lethal. The most common side effects include sedation, dizziness, and sialorrhea during sleep; the most serious are agranulocytosis, seizures and respiratory depression. Although side effects from clozapine are not necessarily preventable, they are for the most part manageable. Even with the most serious adverse effects, proper knowledge of the medication's actions, clinical vigilance, and prompt intervention can prevent the occurrence of significant morbidity and mortality as a consequence of clozapine treatment.

Adult↗
PubMed1992

Normal eye tracking is associated with abnormal morphology of medial temporal lobe structures in schizophrenia.

Eye tracking and brain morphology assessed by magnetic resonance imaging were examined in 48 patients in their first episode of schizophrenia and in 15 normal controls. Schizophrenic patients showed higher rates of eye tracking dysfunction and more abnormal brain morphology involving the lateral ventricles, medial temporal lobe (MTL) structures and the frontal-parietal cortex than controls. Enlargement of the lateral ventricles and global rating of abnormal brain morphology were significantly more prevalent in male schizophrenics than female schizophrenics. These findings indicate that abnormalities in a variety of brain regions are present in some schizophrenics during the period shortly after the first hospitalization and could not be a function of treatment or chronic illness. We found no relation between abnormal eye tracking and any single feature of abnormal brain morphology. However, normal eye tracking was significantly associated with MTL abnormalities in schizophrenics, reflecting an inverse association between quality of eye tracking and degree of abnormality in MTL structures. These results suggest that abnormal eye tracking is not mediated by the same processes that lead to structural brain anomalies in schizophrenia.

Adolescent↗
PubMed1992

First-episode psychosis: Part I. Editors' introduction.

Until recently, there has been a conspicuous lack of studies regarding the earliest phases of psychotic illness, with most research on schizophrenia and related disorders focusing on chronically ill patients. Currently, however, a number of investigators have turned their attention toward this topic, exploring the conceptual issues involved in defining the onset of psychosis, using case registers and population-based samples to do crucial epidemiologic studies on the course of schizophrenia, and developing mechanisms for identifying patients with first-episode psychosis and entering them into active research protocols. The issue of the Schizophrenia Bulletin is devoted to articles representing this full range of conceptual and empirical work on first-episode psychosis. The ultimate goal is for researchers working in this area to develop a network to enhance the sharing of concepts and data, with the eventual possibility of developing combined data bases and collaborative studies.

Female↗
PubMed1992

Prospective study of psychobiology in first-episode schizophrenia at Hillside Hospital.

Heterogeneity has been a consistent problem in the research and treatment of schizophrenia. Despite marked variation in the onset, phenomenology, treatment response and outcome of schizophrenic patients, our ability to identify subtypes is remarkably limited. A major problem in schizophrenia research has been the use of cross-sectional study designs and heterogeneous patient samples at different stages of the illness and who have been previously exposed to neuroleptics which have potentially confounding effects on the disease. This study intends to identify biologic correlates of the phenomenology and course of schizophrenia by using a prospective, longitudinal, repeated measures design assessing biologic and clinical parameters including measures of psychopathology, side effects, and social adjustment to examine clinical variables of treatment response, illness course, and outcome; measures of central nervous system dopamine activity and brain morphology in patients, from the onset of their illness. Patients were ascertained at hospital admission and assessed with a battery of clinical, neuropsychologic, and biologic measures before undergoing standardized treatment for the acute and maintenance phases of the illness. Upon completion, approximately 120 first-episode patients will have entered the study and will have been followed prospectively for up to 5 years and assessed at specific time intervals. Preliminary results reveal significant abnormalities in brain morphology, growth hormone secretion, eye movement function, and psychotogenic response to dopamine agonists in first-episode, treatment-naive patients which are associated with treatment response and outcome. This article describes the study's rationale, design, and methods, and a summary of the published results to date. These are discussed in terms of their significance for putative clinical subtypes and pathophysiological models of schizophrenia.

Adolescent↗
PubMed1992

Intellectual deficits in first-episode schizophrenia: evidence for progressive deterioration.

The developmental processes leading to neuropsychological deficits in schizophrenia are poorly understood. Both early developmental defects and subsequent deterioration may occur. Intelligence test profiles are often used to estimate premorbid ability and deterioration from prior levels of functioning. These characteristics were assessed in samples of first-episode (n = 51) and chronic (n = 50) schizophrenic patients. Although the groups showed few differences on tests to estimate premorbid intellectual ability, the chronic group performed worse on measures considered sensitive to deterioration. Dextral (right-handed) patients tended to have better performance; this effect was marked in the first-episode sample, especially on verbal tests. Male patients showed more evidence of deterioration than female patients. Subgroups differing in the time course of premorbid social dysfunction also differed in intelligence test profiles, suggesting that estimates of social and cognitive deterioration may have concurrent validity. The results support the hypothesis that patients differ in the course of cognitive decline and suggest that deterioration of function may follow the onset of overt psychosis in some patients. Prospective longitudinal studies of first-episode schizophrenic patients could directly test this hypothesis.

Adolescent↗
PubMed1992

Duration of psychosis and outcome in first-episode schizophrenia.

OBJECTIVE: This study was undertaken to assess the potential effect of duration of untreated illness on outcome in a group of first-episode schizophrenic patients. METHOD: Seventy patients with schizophrenia diagnosed according to the Research Diagnostic Criteria entered the study and were followed for up to 3 years. All patients received standardized treatment and uniform assessments both during the acute phase of their illness and throughout the follow-up period. Outcome was measured in terms of time to remission of acute psychotic symptoms as well as degree of symptom remission. RESULTS: The mean duration of psychotic symptoms before initial treatment was 52 weeks, preceded by a substantial prepsychotic period. According to survival analysis, duration of illness before treatment was found to be significantly associated with time to remission as well as with level of remission. The effect of duration of illness on outcome remained significant when diagnosis and gender variables, themselves associated with outcome, were controlled in a regression analysis. Duration of illness was not correlated with age at onset, mode of onset, premorbid adjustment, or severity of illness at entry into the study. CONCLUSIONS: Duration of psychosis before treatment may be an important predictor of outcome in first-episode schizophrenia. Acute psychotic symptoms could reflect an active morbid process which, if not ameliorated by neuroleptic drug treatment, may result in lasting morbidity. Further implications of these findings are discussed.

Adult↗
PubMed1992

On the possible mechanisms and predictability of clozapine-induced agranulocytosis.

Studies were conducted on serum removed from 15 patients before, during, and after, clozapine-induced agranulocytosis. Cytotoxic studies were compared with samples taken from patients during treatment with clozapine who did not develop agranulocytosis or treatment controls (TC); additional controls consisted of allogeneic (NC) and autogeneic serum from apparently normal people. The effect of serum on measurable functions of polymorphonuclear neutrophils (PMNs) taken from normal people was tested. Procedures under study included suppression of post-phagocytosis-induced 14CO2-indicated respiratory burst, as well as ejection of trypan blue by test PMNs. PMNs exposed to active agranulocytosis serum plus complement displayed diminished 14CO2 emission during phagocytosis or failed to eject trypan blue. PMNs exposed to serum of TC and NC continued to function normally as regards 14CO2 emission and trypan blue ejection. Five patients studied before the development of agranulocytosis showed suppressed PMN function, which increased to peak value during agranulocytosis and then disappeared within 40 days of recovery. Similar suppression of colony forming units of granulocytes and macrophages (CFU-GM) was found whenever agranulocytosis serum was included in the marrow culture. The cytotoxic material required complement for its full expression, was not dialysable, was neutralised by anti-IgM serum, and was absorbed by test PMNs. Furthermore, solutions of clozapine or 5 of its metabolites offered no similar suppression of PMN function in vitro after incubation in an aqueous medium or with normal serum. These observations favour development of an immunogenic clone in sensitive people during active treatment with clozapine, which eventually leads to precipitous depletion of PMNs and their precursors. The early appearance of this suppressive substance may offer an early warning for development of agranulocytosis.

Agranulocytosis↗
PubMed1992

Antipsychotic medication effects on neuropsychological functions.

The investigator of antipsychotic drug effects on neuropsychological functions faces a range of conceptual, methodological, and technical obstacles. Some of these hurdles are pointed out in a brief review of existing literature, and a more detailed consideration of instrumentation issues is presented. The need for hypothesis-driven assessment strategies is highlighted. Interpretive difficulties are posed by the polyfactorial nature of the most widely used neuropsychological tests, and emphasis is placed on the use and development of methods that enable isolation of specific neuropsychological constructs. Examples of this strategy are drawn from ongoing work in the Neuropsychology Unit of the Clinical Research Center for the Study of Schizophrenia at Hillside Hospital, where hypotheses about the behavioral site of action of dopamine agonists and antagonists are used to guide the construction of novel computerized tests.

Animals↗
PubMed1992

Cytotoxic activity in serum of patients with clozapine-induced agranulocytosis.

Studies were conducted on serum samples collected from 15 patients during the course of clozapine-induced agranulocytosis. During acute phases of agranulocytosis, serum was cytotoxic to peripheral polymorphonuclear neutrophils (PMNs), as indicated by complement-dependent suppression of postphagocytosis respiratory burst and by increased retention of trypan blue dye by test PMNs. Cytotoxicity was removed by adsorption with allogeneic PMNs, was attenuated by antibody to immunoglobulin M but not by antibody to immunoglobulin G antigen-binding fragment, was not dialyzable, and was partially removed by 2-mercaptoethanol and dialysis. Three patients in a longitudinal study all had perturbed postphagocytosis respiratory burst 20 days before agranulocytosis developed. In all patients cytotoxicity disappeared less than 40 days after treatment when the offending drug was discontinued. Trypan blue dye reactivity was similar when tested. At 20% of culture medium, all serum samples partially suppressed development of colony-forming units of granulocytes and macrophages (CFU-GM) in marrow cultures. At 40% of culture medium, agranulocytosis serum suppressed CFU-GM completely but did not inhibit development of colony-forming units of erythroblasts (CFU-E) or burst-forming units of erythroblasts (BFU-E). Addition of clozapine alone or to agranulocytosis serum neither enhanced nor suppressed toxicity to peripheral PMNs. Neither clozapine nor its toxic metabolic end-products directly produced equivalent cytotoxicity to cellular function or proliferation at 10(-5)mol/L. Serum from patients given clozapine who did not have agranulocytosis and samples from allogeneic normal subjects were not cytotoxic to test PMNs. Cytotoxicity was specific to granulocyte cell lines because development of CFU-GM was inhibited by agranulocytosis serum, whereas CFU-E and BFU-E were not similarly affected. Further studies are in progress to distinguish between immunogenic and non-immunogenic mechanisms.

Adult↗
PubMed1992

Incidence and correlates of acute extrapyramidal symptoms in first episode of schizophrenia.

The incidence and correlates of extrapyramidal symptoms (EPS) in neuroleptic treatment of schizophrenic patients have been reported for chronic patients but not for first-episode patients. We examined the incidence and correlates of extrapyramidal symptoms in a cohort of 70 treatment-naive patients who received fluphenazine at 20-40 mg/day for the first 10 weeks of treatment. Thirty-four percent of our sample developed parkinsonism, 18 percent developed akathisia, and 36 percent developed dystonia. Acute EPS were associated with greater baseline psychopathology. Acute EPS were also associated with better treatment outcome in terms of time to and level of remission. These findings suggest that the EPS response of neuroleptic-naive patients may differ from that of chronically ill patients and that acute EPS status may be an indicator of pharmacologic responsivity in this group.

Acute Disease↗
PubMed1991

Prospective study of tardive dyskinesia incidence in the elderly.

OBJECTIVES: To investigate the incidence of tardive dyskinesia in elderly individuals beginning treatment with antipsychotic drugs and to identify risk factors for the development of tardive dyskinesia in the elderly. DESIGN: A cohort of previously neuroleptic-naive patients was identified at the time of initiation of antipsychotic drug treatment. Patients were evaluated at baseline and followed up at 3-month intervals for periods ranging from 3 to 119 weeks. SETTING: Subjects were recruited from the psychiatric and geriatric medical services of two medical centers, a geriatric institute, and three nursing homes in the metropolitan area of New York City, NY. PATIENTS: Two hundred fifteen individuals older than 55 years have entered the study thus far. Preliminary data are presented for 160 patients who were followed up for at least 1 month. Their age range was 57 to 99 years (mean, 77 years). Seventy-two percent were women and 87% were white. Sixty-seven percent of patients had a diagnosis of organic mental syndrome and 42% had a psychiatric diagnosis. INTERVENTIONS: A naturalistic, longitudinal, repeated assessment paradigm was employed. Assessments included abnormal involuntary movements, extrapyramidal signs, psychiatric symptoms, and medical and drug treatment histories. MAIN OUTCOME MEASURE: The incidence of tardive dyskinesia was determined using a standardized rating instrument and survival analysis. RESULTS: The incidence of neuroleptic-induced dyskinesia was 31% (95% confidence interval, 20%, 42%) after 43 weeks of cumulative neuroleptic treatment. Psychiatric (as opposed to organic) diagnosis and presence of extrapyramidal signs early in treatment were associated with increased tardive dyskinesia vulnerability.

Age Factors↗