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Biomedical subjects

J A Lieberman

Publications and source records attributed to J A Lieberman.

At least 109 records · Page 6Linked to original sources
PubMed1996

Compliance issues in primary care.

Primary care medical practice is a broadly based medical discipline, emphasizing continuity of care in both sickness and health and effective doctor/patient communication and involving the patient as a partner in the provision of health care services. Against this background, there is troubling evidence that psychosocial (mental health) problems are not being adequately diagnosed and treated by physicians in general, and primary care practitioners in particular. This deficiency is the first step down the road to poor compliance. This author assumes that a goodly portion of the blame can be laid on the doorstep of the medical education establishment with its emphasis on the biomedical, reductionism, and high-tech tertiary care. Physicians exit the educational system with a predisposition to deal with problems from a biomedical perspective. They are unaware that, by the very nature of the doctor/patient relationship, they possess considerable ability to effectively intervene in the psychosocial area. Suggestions are given as to how primary care practitioners can improve on this dimension of their medical practice and deal with psychosocial issues. Available evidence would indicate that effectively dealing with these issues will improve patient compliance and outcomes.

Attitude to Health↗
PubMed1996

Factors influencing treatment response and outcome of first-episode schizophrenia: implications for understanding the pathophysiology of schizophrenia.

For the majority of patients, schizophrenia is a chronic recurrent disease that leads to significant residual morbidity which occurs through a process of behavioral deterioration. The factors that influence the course of schizophrenia after its onset and the ability of treatment to modify the effects of the patient's illness are not well understood. This article examines specific clinical and biological variables that are associated with treatment response and outcome. These variables, which are both trait and state dependent, include premorbid adjustment, age and mode of onset of illness, gender, duration of psychosis, schizophrenia subtype, primary negative symptoms, and extrapyramidal signs including tardive dyskinesia and plasma HVA and brain pathomorphology. In addition, the chronic effects of antipsychotic drug treatment may influence illness course both favorably and adversely as well as potentially altering the neurobiological substrates that mediate expression of the illness and treatment response. Finally, the question of whether the active phase of the illness involves a pathologic process that leads to illness progression is discussed. In light of this discussion, we can speculate that although certain aspects of the illness in terms of its severity and course may be, to an extent, predetermined, a number of factors can exert favorable and unfavorable effects on the course of the illness and its ultimate outcome. One question for the field is to develop therapeutic strategies that minimize the morbidity of the illness in a way that does not introduce iatrogenic consequences to the patient.

Adult↗
PubMed1996

Atypical antipsychotic drugs as a first-line treatment of schizophrenia: a rationale and hypothesis.

Clozapine represented the first significant advance in the pharmacotherapy of schizophrenia since the introduction of conventional antipsychotic drugs in the 1950's. Despite its superior efficacy and potential to reduce substantially the morbidity of schizophrenia and improve the outcomes, of patients, clozapine has not been used on a widespread basis or as a first-line treatment due to its potential for agranulocytosis. With the introduction of risperidone and the imminent prospect of other atypical antipsychotic drugs (olanzapine, sertindole, quetiapine, ziprasidone), clinicians may be able to improve dramatically the methods and manner in which they treat schizophrenia and related psychotic disorders. If we accept the premise that atypical antipsychotic drug provide superior efficacy, reduced side effects, and the prospect of better compliance, their greatest impact may be when used in patients at the beginning of their illness. The following article provides a rationale and hypothesis for the use of atypical antipsychotic drugs as a first-line treatment of schizophrenia.

Adolescent↗
PubMed1995

The major histocompatibility complex region marked by HSP70-1 and HSP70-2 variants is associated with clozapine-induced agranulocytosis in two different ethnic groups.

Genes of the major histocompatibility complex (MHC) have been associated with susceptibility to drug-induced adverse reactions. We previously found that clozapine-induced agranulocytosis (CA) is associated with the HLA-DRB1*0402, DRB4*0101, DQB1*0302, DQA1*0301 haplotype in Ashkenazi Jewish patients and with the HLA-DRB1*1601, DRB5*02, DQB1*0502, DQA1*0102 haplotype in non-Jewish patients. In the present study, we tested the hypothesis that the variants of the heat-shock protein 70 (HSP-70) encoded by the HSP-70 loci located within the MHC region and known to be involved in apoptosis and regulation of cell proliferation could play an important role in molecular mechanisms of CA. First, we analyzed HSP70-2 polymorphism in risk-associated haplotypes from HLA homozygous cells and normal individuals and confirmed that the HSP70-2 9-kb variant was associated invariably with DR4 (HLA-DRB1*0402, DQB1*0302) and DR2 (HLA-DRB1*01601, DQB1*0502, DQA1*0102 and HLA-DRB1*1501, DQB1*0602) haplotypes, which were the haplotypes found increased in Jewish and non-Jewish patients with CA, respectively. The 9.0-kb variant was also found to be associated with HLA-B44, DRB1*0401 and HLA-B44, DRB1*07 haplotypes. Second, in patients with CA (12 Ashkenazi Jewish and 20 non-Jewish patients), HSP70-1 A and HSP70-2 9.0-kb variants were associated with the MHC haplotypes found by us to be markers of susceptibility to CA. The clozapine-treated control group had an excess number of HSP70-1 C and HSP70-2 8.5-kb variants, consistent with genetic resistance to CA associated with those variants. This finding supports our hypothesis that a dominant gene within the MHC region (marked by HSP70-1 and HSP70-2), but not necessarily HLA, is associated with CA in two different ethnic groups.

Agranulocytosis↗
PubMed1995

HLA associations in clozapine-induced agranulocytosis.

We previously reported preliminary results of association of clozapine-induced agranulocytosis (CA) with HLA-B38, DR4, DQ3 in five Ashkenazi Jewish patients and with HLA-DR2, DQ1 in four non-Jewish patients. In the present study, 31 additional patients with CA, 10 Ashkenazi Jewish, and 21 of non-Jewish ancestry, were studied. HLA alleles and haplotypes were compared among 52 patients (33 Ashkenazi Jewish, 19 non-Jewish) matched for ethnic background and clinical status. Our results show two associations and define the HLA allele markers for the Ashkenazi Jewish and non-Jewish haplotypes associated with CA. The most important markers for susceptibility for CA in Ashkenazi Jewish patients were DRB1*0402, DQB1*0302, and DQA1*0301, and in non-Jewish patients, HLA-DR*02, DQB1*0502, and DQA1*0102. HLA-DRB1*011 and DQB1*0301 were underrepresented in Ashkenazi Jewish patients when compared with controls. We hypothesize that genes of the major histocompatability complex, other than class I and class II, are responsible for CA; among them are the variants of the heat-shock proteins 70 or the tumor necrosis factor loci.

Adult↗
PubMed1995

Cerebellar volume asymmetries are related to handedness: a quantitative MRI study.

Four cerebellar subregions were delineated (left, right; anterior, posterior), and their volumes measured on contiguous 3.1 mm coronal MR images in 15 dextral and 8 nondextral healthy control subjects. (1) Left and right cerebellar hemisphere volume asymmetries interacted with anterior-posterior level (anterior: right > left; posterior: left > right), following a pattern commonly found in the neocortex; (2) A significant handedness effect was found (P < or =0.01) on a composite index of cerebellar asymmetry, such that dextrals showed more asymmetry than nondextrals. These data suggest that the same pattern of asymmetries observed at the neocortical level is also present in the metencephalon. These asymmetries, possibly resulting from multiple developmental growth gradients acting on the metencephalon early in gestation, are associated with handedness differences in adulthood.

Adult↗
PubMed1995

Anterior hippocampal volume reductions predict frontal lobe dysfunction in first episode schizophrenia.

This study examined relations of mesiotemporal lobe tissue volumes with neuropsychological (NP) functions in a sample of patients with first episode schizophrenia. Three contiguous compartments of the mesiotemporal lobe were measured on magnetic resonance images, comprising primarily amygdaloid, anterior hippocampal, and posterior hippocampal tissue volumes. NP measures were derived from a comprehensive battery. Decreased volume selectively in the anterior hippocampal formation was associated with lower scores on measures of executive and motor functions usually considered sensitive to the integrity of frontal lobe systems. Measures of other NP functions, and global intellectual ability, were not related to mesiotemporal volumes. The findings that morphologic abnormalities in the mesiotemporal lobe are associated with impairment of frontal lobe functions point to a defect in an integrated functional system that includes both frontal and mesiotemporal components. The findings are consistent with the hypothesis that neurodevelopmental defects affecting the morphology of the anterior hippocampal formation may be manifest later in life as impairments in fronto-limbic control. .

Acute Disease↗
PubMed1995

Clinical implications of clozapine discontinuation: report of an NIMH workshop.

In September 1994, the National Institute of Mental Health convened a group of scientists to discuss the clinical effects of rapid clozapine discontinuation, especially in light of the introduction of risperidone for the treatment of schizophrenia. Despite concern over recent reports of clinical deterioration (psychotic exacerbations, somatic withdrawal symptoms, and extrapyramidal side effects) in a few patients abruptly discontinued from clozapine, there is currently insufficient information to determine the magnitude of the problems associated with clozapine withdrawal. However, clinicians are reminded that the withdrawal schedule for clozapine indicates a gradual tapering schedule (unless the patient is experiencing severe side effects); that switching patients from clozapine to risperidone does not mean that such tapering is unnecessary; and that the use of risperidone may not produce all of the same effects as clozapine in some treatment-refractory patients.

Antipsychotic Agents↗
PubMed1995

Free radical scavenging enzyme activity and related trace metals in clozapine-induced agranulocytosis: a pilot study.

We hypothesized that patients who had experienced clozapine-induced agranulocytosis would have abnormalities in their free radical scavenging enzyme activity (FRESA) and levels of related trace metals. We therefore measured FRESA profiles and related trace metals in four groups: post-clozapine agranulocytosis (POST CLOZ AGRAN) (N = 9); clozapine no agranulocytosis (CLOZ NO AGRAN) (N = 12); West Coast controls (WC CONTROLS) (N = 14); and Long Island Jewish Medical Center controls (LIJ CONTROLS) (N = 12). Glutathione peroxidase (GSH-Px, P1) levels in plasma were slowest in the POST CLOZ AGRAN group (34.3 +/- 6.9 IU/dl [standard deviation; SD]; p < 0.002); red blood cell glutathione peroxidase (GSH-Px, RBC) was highest in the WC CONTROLS (38.7 +/- 4.7 IU/g hemoglobin [Hgb]; p < 0.008); and selenium (SE) levels in plasma were lower in both the POST CLOZ AGRAN group (111.6 +/- 14.7 ng/ml) and the CLOZ NO AGRAN group(115.0 +/- 17.8) than in the WC CONTROLS (142.5 +/- 18.3; p < 0.0006). SE was also lower in the POST CLOZ AGRAN group than in the LIJ CONTROLS (129.1 +/- 21.6; p < 0.04). The presence of at least one of the following: (1) GSH-Px, P1 < 37.6 IU/dl; (2) GSH-Px, RBC < 31.0 IU/g Hgb; or (3) SE < 112.4 ng/ml, distinguished POST CLOZ AGRAN subjects from the WC CONTROLS, but not from the LIJ CONTROLS. Data from this cross-sectional pilot study suggest that abnormalities in the body's antioxidant defense system may be involved in the pathogenesis of clozapine-associated agranulocytosis. If confirmed in large-scale, prospective studies, these preliminary findings have potential clinical application in the screening and prophylaxis of clozapine agranulocytosis.

Adult↗
PubMed1995

Prevalence and clinical correlates of extrapyramidal signs and spontaneous dyskinesia in never-medicated schizophrenic patients.

OBJECTIVE: This study assessed the prevalence of extrapyramidal signs and spontaneous dyskinesia in neuroleptic-naive, first-episode schizophrenic patients and examined the clinical correlates. METHOD: In a prospective study of the psychobiology of schizophrenia, the authors examined 89 neuroleptic-naive patients for the presence of extrapyramidal signs by using the Simpson-Angus Rating Scale and for dyskinesia by using the Tardive Dyskinesia Rating Scale. RESULTS: Fifteen patients (16.9%) had extrapyramidal signs, but only one had spontaneous dyskinesia at baseline. Presence of extrapyramidal signs was correlated with more negative symptoms and poorer treatment outcome that was reflected in a longer time to and lower level of remission. There was no correlation of spontaneous extrapyramidal signs with age of patient, age at onset of psychotic symptoms, or baseline psychopathology. There was no difference between patients with and without spontaneous extrapyramidal signs in terms of the subsequent development of persistent tardive dyskinesia, but the patients with spontaneous extrapyramidal signs were more likely to develop parkinsonian side effects after 8 weeks of antipsychotic treatment. CONCLUSIONS: Extrapyramidal signs are present in a proportion of neuroleptic-naive, first-episode schizophrenic patients, which suggests an involvement of these signs in the schizophrenic process that probably reflects basal ganglia pathology. The presence of spontaneous extrapyramidal signs seems to have prognostic significance insofar as it is linked to a poorer outcome and longer time to remission. Spontaneous dyskinesia appears to be a relatively rare finding.

Adolescent↗
PubMed1995

Plasma clozapine levels and clinical response for treatment-refractory schizophrenic patients.

OBJECTIVE: The purpose of this study was to determine if plasma clozapine levels were associated with treatment response. METHOD: To examine this question, neuroleptic nonresponsive patients with schizophrenia or schizoaffective disorder were given clozapine, which was titrated to 500 mg/day by day 14 of treatment, and the dose was held fixed at least through day 21. Subsequently, clozapine doses were adjusted as clinically indicated, up to a maximum of 900 mg/day. Plasma clozapine levels were obtained at weeks 3 and 6, and standard clinical ratings (Brief Psychiatric Rating Scale [BPRS] and Clinical Global Impression) were done at baseline and at weeks 3 and 6. RESULTS: Data from 45 subjects were analyzed. There were no correlations between plasma clozapine levels and change in BPRS scores at treatment weeks 3 and 6. However, when the subjects were classified as responders or nonresponders, therapeutic response was associated with clozapine blood levels above 350 ng/ml. CONCLUSIONS: This study suggest that clozapine blood levels are correlated with clinical response.

Adult↗
PubMed1995

Postictal and chronic psychoses in patients with temporal lobe epilepsy.

OBJECTIVE: This study sought to elucidate the relation of clinical, neuropsychological, and seizure variables to chronic and postictal psychoses in patients with temporal lobe epilepsy. METHOD: Forty-four patients with treatment-refractory temporal lobe epilepsy were given formal psychiatric evaluations; 29 patients had no psychiatric disorder or a nonpsychotic disorder, eight patients had postictal psychoses, and seven patients had chronic psychoses. Comparisons of clinical, neuropsychological, magnetic resonance imaging, and seizure variables were made between the nonpsychotic and the psychotic patients and, secondarily, between the patients with transient postictal psychoses and those with chronic psychoses. RESULTS: Bitemporal seizure foci, clustering of seizures, and absence of febrile convulsions were associated with both postictal psychoses and chronic psychoses. Younger age at onset of epilepsy and lower verbal and full-scale IQs differentiated the patients with chronic psychoses from those with postictal psychoses. CONCLUSIONS: Patients with temporal lobe epilepsy with chronic and postictal psychoses show similar profiles of clinical and seizure variables, suggesting shared etiologic factors. These factors may increase the propensity to develop psychotic symptoms, while other factors, such as time of onset of epilepsy and underlying neuropathology, may determine whether transient or chronic psychotic symptoms develop. Even among patients with treatment-refractory temporal lobe epilepsy, a specific subgroup of patients, characterized by bitemporal seizure foci, an absence of febrile convulsions, and a history of clustering of seizures, appears to be particularly prone to develop psychotic disorders. A process similar to secondary epileptogenesis may be involved in the development of the psychoses.

Adult↗