PubMed Health⌕ Search

Biomedical subjects

J A Lieberman

Publications and source records attributed to J A Lieberman.

At least 127 records · Page 7Linked to original sources
PubMed1995

Gender differences in onset of illness, treatment response, course, and biologic indexes in first-episode schizophrenic patients.

OBJECTIVE: Gender differences in onset of illness, response to treatment, course, and biologic measures have been consistently reported in patients with chronic schizophrenia. Patients with first-episode schizophrenia were examined to determine whether gender differences also occur in these patients. METHOD: Fifty-four neuroleptic-naive schizophrenic patients (29 men and 25 women) were studied beginning in an initial stage of the first hospitalization for psychosis while undergoing treatment with a standardized medication regimen. Before antipsychotic drug treatment and during 1 year of follow-up each patient was rated on the Schedule for Affective Disorders and Schizophrenia--Change Version (psychosis and disorganization items), Scale for the Assessment of Negative Symptoms, Clinical Global Impression, modified Simpson Tardive Dyskinesia Scale, and Simpson-Angus Rating Scale for extrapyramidal side effects. Methylphenidate challenge testing was done at study entry. Plasma neuroleptic, homovanillic acid (HVA), and prolactin levels were determined weekly for the first 6 weeks. RESULTS: The female schizophrenic patients had a later onset and better treatment response than the men. Plasma HVA levels at baseline and week 1 and changes in prolactin levels from baseline to weeks 1 through 6 were greater among the women. CONCLUSIONS: Gender differences in onset and degree of treatment response in first-episode schizophrenic patients are similar to those of chronic patients and are apparent at early stages of the illness. The greater pharmacologic responsivity of the female patients, as indicated by the neuroendocrine results, is consistent with the gender difference in degree of symptom improvement with medication.

Adolescent↗
PubMed1995

Do white-cell count spikes predict agranulocytosis in clozapine recipients?

The use of clozapine is limited by the risk of agranulocytosis. The incidence of agranulocytosis after 1 year was .80 percent in 11,555 patients registered in the Clozaril Patient Management System (CPMS) who received clozapine from February 1990 to April 1991. We noticed a tendency for white-cell counts to spike upward before agranulocytosis occurred. We analyzed the CPMS data to test whether a white-cell count spike at least 15 percent above the previous measurement predicted agranulocytosis within 75 days, with a 21-day lag to allow white-cell counts to decline to levels indicative of agranulocytosis. The occurrence of a spike, entered as a time-dependent covariate in proportional hazards regression, significantly predicted development of agranulocytosis (risk ratio, 3.02; 95% confidence interval, 1.38 to 6.57). Spikes were sensitive though nonspecific predictors, occurring frequently in patients who did not develop agranulocytosis. These results, while exploratory, indicate the potential usefulness of these spikes as guidelines to govern the use of clozapine.

Agranulocytosis↗
PubMed1995

A comparison of European and American dosing regimens of schizophrenic patients on clozapine: efficacy and side effects.

We present a comparison of the results from two studies of patients on clozapine. The American study (n = 84; Hillside Hospital, Glen Oaks, NY) and the European study (n = 63; Innsbruck University Clinics, Innsbruck, Austria) both examine efficacy and side effects in schizophrenic patients on this atypical neuroleptic. There is a very substantial difference in the dosing regimen used on both continents and this is reflected in the studies reported. A question with major clinical implications is whether the higher doses commonly used in the United States lead to a better outcome or a different profile of side effects. Outcome as a function of serum concentration will be examined. Results confirm a lower dose, lower clozapine blood level, and a lesser degree of side effects in the Austrian cohort when compared to the American sample. Surprisingly, the clinical efficacy of the lower dosing regimen was superior to the higher dose. Reasons for this anomaly are explored.

Adult↗
PubMed1995

Neuroleptic treatment of elderly patients.

Data from an ongoing longitudinal study of the development of tardive dyskinesia were analyzed to examine the indications for neuroleptic treatment, continuity of treatment and dosage, and the effects of treatment on ratings of psychopathology and cognitive functioning during the first year of followup. Subjects were 266 elderly patients who had just begun neuroleptic treatment. Patients were predominantly (75%) female; their mean (+/- SD) age was 76.9 (+/- 9.2) years. A psychiatric diagnosis was recorded for 44 percent, primarily major depressive disorder; organic mental syndrome was diagnosed in 65 percent of the patients. Symptom ratings indicated 82 percent of the patients had psychosis, with or without agitation. Haloperidol was prescribed for 68 percent of the patients. Most were on neuroleptic medication continuously during the first month of followup; the average starting dose was 80 mg/day in chlorpromazine equivalent units. Symptom ratings at 1 month and 6 months showed significant improvement from baseline; ratings of dementia were unchanged.

Aged↗
PubMed1994

Dopamine D4 receptor variant, D4GLYCINE194, in Africans, but not in Caucasians: no association with schizophrenia.

Because antipsychotic drugs selectively block dopamine receptors and since dopamine D4 receptors are elevated sixfold in postmortem schizophrenia brain, we searched for possible abnormalities in the coding region of the genomic DNA sequence for the dopamine D4 receptor in control and schizophrenia tissues. The DNA sequence for the first 250 bases of exon 3 of this receptor was examined in the genomic DNA from 296 control individuals and 58 schizophrenics. Twenty-three out of 183 control blacks (12.6%) and 3 out of 24 (12.5%) schizophrenic blacks revealed a replacement of T by G, predicting a substitution of valine by glycine at amino acid position 194. The identical prevalence of 12.5% indicates that the variant is not associated with schizophrenia. The amino acid replacement occurs one amino acid away from a serine amino acid which is critical for the attachment of dopamine. None of the 147 Caucasians (113 controls; 34 schizophrenics) revealed this variant, termed D4GLYCINE194.

Adult↗
PubMed1994

Methylphenidate response, psychopathology and tardive dyskinesia as predictors of relapse in schizophrenia.

Despite the proven efficacy of acute and maintenance pharmacotherapy in schizophrenia, practical methods for identifying patients who require continuous treatment to prevent relapse have not been established. We hypothesized that a pathologic overactivity of mesolimbic and mesocortical dopamine neural systems, that mediates positive psychotic symptoms in the acute phase of the illness, persists in some outpatients who are vulnerable to relapse despite appearing clinically stable. To test and determine if putative measures of central nervous system dopamine activity predict outcome, 41 stable outpatients receiving neuroleptic maintenance treatment underwent provocative tests with methylphenidate in a randomized double-blind placebo controlled design in which behavioral, neuromotor, biochemical, and cardiovascular responses were measured. Patients were then withdrawn from medication and monitored for 52 weeks, or until relapse. The results indicate that psychotic symptoms and their activation by methylphenidate, and the presence of tardive dyskinesia are associated with each other and with a higher risk of relapse. These findings partially support our hypothesis and offer potentially useful measures for the identification of candidates for reduced dose neuroleptic maintenance treatment strategies in schizophrenia.

Adolescent↗
PubMed1994

Women are at greater risk than men for malpositioning of the endotracheal tube after emergent intubation.

OBJECTIVES: To investigate the occurrence of endotracheal tube malpositioning after emergent intubation in critically ill adults and to determine the need for a routine postintubation chest radiography to assess endotracheal tube position. DESIGN: Prospective study. SETTING: All adult critical care and acute care units of a 560-bed university teaching hospital. PATIENTS: Study of 297 consecutive intubations (185 intubations in males and 112 intubations in females) in 238 adult patients. METHODS: Emergent endotracheal intubations were performed by resident physicians with supervision from an intensive care unit (ICU) or anesthesia attending physician or an anesthesia resident. After intubation, proper positioning of the endotracheal tube was verified by the intubating physician using clinical criteria, including auscultation of bilateral breath sounds, symmetric chest expansion, and palpation of the endotracheal tube cuff in the suprasternal notch. The endotracheal tube position relative to the lower anterior incisors or alveolar ridge was recorded using the centimeter markings printed on the endotracheal tube. A chest radiograph was obtained after intubation to verify endotracheal tube position. Appropriate endotracheal tube position on chest radiograph was defined as between > 2 and < or = 6 cm above the carina. MEASUREMENTS AND MAIN RESULTS: Of the 297 intubations, 26 were excluded from analysis because a chest radiograph was not obtained or the patient was not of normal stature. For the remaining 271 intubations, 42 (15.5%) endotracheal tubes were inappropriately placed, according to the radiographic assessment. The percentage of malpositioned endotracheal tubes was significantly higher in women than in men (61.9% vs. 38.1%, respectively; chi-square: p < .001). Thirty-three (78.6%) of 42 malpositioned endotracheal tubes were placed < 2 cm from the carina, with the highest occurrence (24/33) of proximal malposition occurring in women. Positioning of endotracheal tubes using the centimeter markings printed on the tube referenced to the lower incisors did not accurately identify malposition as documented by chest radiograph. CONCLUSIONS: Emergent endotracheal intubations result in a significant occurrence of malpositioned endotracheal tubes that are undetected by clinical evaluation. Malpositioning is not detected by routine clinical assessment, but only by chest radiograph. Women are at greater risk than men for endotracheal tube malpositioning after emergent intubation; in women, the endotracheal tube is more likely to be positioned too close to the carina. A chest radiograph for confirmation of endotracheal tube position after emergent intubation should remain the standard of practice.

Adult↗
PubMed1994

The deficit state in first-episode schizophrenia.

OBJECTIVE: The prevalence, clinical correlates, and outcome of the deficit syndrome were determined for 70 patients ascertained in their first episode of schizophrenia and then followed through their recovery. METHODS: Patients were treated in a standardized manner and underwent baseline assessments of symptoms and adverse effects that were repeated at intervals throughout their inpatient and subsequent outpatient course. Forty-seven patients were followed for a minimum of 6 months after remission of their positive symptoms, allowing for an assessment of their deficit syndrome status. RESULTS: Using modified criteria of Carpenter et al. for the deficit syndrome, the authors found that two patients (4%) met all criteria for the deficit syndrome, nine (19%) had deficit symptoms (questionable deficit state), and 36 (77%) had no deficit symptoms. When patients who had not fully remitted or had remitted for less than 6 months were included, seven (10%) met deficit syndrome criteria, 11 (16%) had deficit symptoms, and 52 (74%) had no deficit symptoms. CONCLUSIONS: The prevalence of the deficit syndrome in first-episode schizophrenia varies depending on the criteria used and is lower than that previously described in more chronic patient samples. Patients without deficit symptoms had better premorbid functioning and a better global outcome than patients with deficit symptoms.

Adult↗
PubMed1994

Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs.

OBJECTIVE: This study examined the pathomorphology of the caudate nuclei in first-episode schizophrenic patients with minimal previous neuroleptic exposure. METHOD: Magnetic resonance imaging (MRI) of the brain was used to examine longitudinally the caudate pathomorphology in 29 first-episode schizophrenic patients and 10 healthy comparison subjects. MRI scans were obtained after the subjects entered the study and at 18-month follow-up. The patients were treated with standardized neuroleptic regimens during the 18-month period. Volumetric assessments of the cerebral cortex, lateral ventricles, and caudate nuclei were performed on T1-weighted coronal brain sections. In addition, the patients were systematically evaluated for psychopathology at baseline and during treatment. RESULTS: Caudate volumes increased 5.7% in the patients during the 18-month treatment interval, whereas they decreased 1.6% in the comparison subjects over the same time period. Greater amounts of antipsychotic medication received by patients before the first scan and younger age at the time of the first scan were associated with larger increases in caudate volume. CONCLUSIONS: Caudate enlargement occurs early in the course of treatment in young first-episode schizophrenic patients. This may be a result of an interaction between neuroleptic treatment and the plasticity of dopaminergic neuronal systems in young patients.

Adult↗
PubMed1994

Absence of regional hemispheric volume asymmetries in first-episode schizophrenia.

OBJECTIVE: The goal of this study was to determine whether patients experiencing their first episode of schizophrenia differ from healthy subjects in regional cerebral hemispheric volumes or asymmetries. METHOD: Regional volumes corresponding to prefrontal, premotor, sensorimotor, occipitoparietal, and temporal lobes in each hemisphere were measured on contiguous coronal magnetic resonance images in 70 patients experiencing their first episode of schizophrenia and in 51 healthy comparison subjects. RESULTS: Patients did not differ from the comparison subjects in regional or total hemispheric volumes, but they had abnormal hemispheric asymmetries. Subjects in the comparison group had significant lateral asymmetries in each region: their occipitoparietal and sensorimotor regions were larger on the left, and their premotor, prefrontal, and temporal regions were larger on the right. Patients lacked lateral asymmetries and showed significantly less asymmetry than healthy subjects in occipitoparietal, premotor, and prefrontal regions. Absence of the normal asymmetry was more common among patients initially diagnosed with the undifferentiated than with the paranoid subtype of schizophrenia and was associated with more severe negative symptoms among men. Asymmetries were related to sex and handedness regardless of diagnosis; specifically, dextral men showed more asymmetry than nondextral men or dextral women. CONCLUSIONS: The absence of normal hemispheric asymmetries suggests an anomaly in the development of laterally specialized cerebral systems in schizophrenia, and this may be associated with an initial presentation of nonparanoid psychosis.

Adult↗
PubMed1994

Clinical effects of clozapine in chronic schizophrenia: response to treatment and predictors of outcome.

OBJECTIVE: This study addressed the unique clinical properties attributed to the atypical antipsychotic clozapine, including its efficacy in patients with treatment-refractory psychosis and against negative symptoms, its lack of acute extrapyramidal side effects, and the longer time course of its therapeutic effects. METHOD: The clinical responses of 84 schizophrenic inpatients (66 with treatment-refractory illness and 18 who were intolerant of antipsychotic treatment) were examined. After all previous antipsychotic medications had been withdrawn, the patients were treated with clozapine according to a standardized titration and dosage schedule. Patients who tolerated and responded to treatment were discharged and maintained on a regimen of clozapine for up to 52 weeks. Patients were evaluated for behavioral response and side effects after weeks 3, 6, 12, 26, 39, and 52 of treatment. RESULTS: Fifty percent of the patients with treatment-refractory illness and 76% of the treatment-intolerant patients responded to clozapine in up to 52 weeks. The optimal period for a trial of clozapine appeared to be 12-24 weeks. Clozapine exhibited therapeutic effects on negative symptoms, but these were not clearly independent of its effects on positive symptoms and extrapyramidal side effects. Several variables, including early age at onset of illness and female gender, were found to be predictors of poor response to treatment. Predictors of good response included the presence of extrapyramidal side effects during previous treatment with classic neuroleptics and a diagnosis of paranoid schizophrenia. CONCLUSIONS: These findings have important implications for the use of clozapine and our understanding of the pathophysiology of treatment-resistant schizophrenia.

Adolescent↗
PubMed1994

Predictors of response to clozapine.

Clinical and biological measures were examined for their relationship to clinical response to clozapine. Associations were found between therapeutic response and the following variables: male gender, paranoid schizophrenia subtype diagnosis, older age at onset of illness, shorter duration of illness, higher levels of pretreatment acute EPS, low pretreatment CSF HVA/5-HIAA, greater decrease in prolactin (PRL) and increase in growth hormone (GH) response to apomorphine stimulation pretreatment and greater inhibition by clozapine treatment of PRL and GH response to apomorphine, and plasma clozapine levels above 350 ng/mL. These results are consistent with other investigators' findings and have practical and heuristic implications for the use of clozapine and understanding its mechanism of action.

Adult↗
PubMed1994

Agranulocytosis: incidence and risk factors.

The use of clozapine has been limited by the risk of agranulocytosis. The cumulative incidence of agranulocytosis is 0.80% after 1 year and 0.91% after 1 1/2 years. Risk is greatest during the first 3 months of treatment and greater among women and the elderly. White-cell counts tend to spike upward before the occurrence of agranulocytosis. The occurrence of a white-cell count spike of > or = 15% above the previous count predicts development of agranulocytosis within 75 days (risk ratio = 3.02; 95% confidence interval, 1.38-6.57). Our results indicate that hematologic monitoring is necessary and effective. They also suggest that the frequency of monitoring could be reduced after the initial period of maximal risk.

Adult↗
PubMed1994

HSP70-2 9.0 kb variant is in linkage disequilibrium with the HLA-B and DRB1* alleles associated with clozapine-induced agranulocytosis.

In order to extend the analysis of the association between class I and class II HLA markers and HSP-70 alleles, we studied the genetic polymorphism of HSP70-2 genes by restriction fragment length polymorphism analysis in a panel of HLA-homozygous cell lines carrying the HLA-B alleles known to be associated with clozapine-induced agranulocytosis. We have found a linkage disequilibrium between the 9.0 kb variant of HSP70-2 with the class I antigens HLA-B7, B38, and B44 and with the class II antigens HLA-DR2 and DR4. We discuss the importance of analyzing the variants of HSP70-2 in patients with agranulocytosis to confirm that the 9.0 kb allele is a genetic marker for the disease. If that is the case, HSP-70 variants could explain the different associations of HLA alleles in individuals of Jewish and non-Jewish ancestry because the HLA alleles are in linkage disequilibrium with the 9.0 kb band. We postulate that HSP-70 molecules could also play a significant role in determining the molecular mechanisms that induce agranulocytosis by clozapine.

Agranulocytosis↗
PubMed1994

Cerebral morphometry and clozapine treatment in schizophrenia.

Studies of brain morphology in schizophrenia may be informative about basic pathophysiologic processes, provide clinically useful indicators of treatment response, and lead to the identification of markers for selective treatment effects. This paper reviews findings from magnetic resonance imaging studies of patients with schizophrenia conducted at Hillside Hospital, with special attention to (1) findings that have helped distinguish patients who respond well to typical neuroleptics from those who have gone on to trials of clozapine, (2) the capacity of morphological measures to predict clozapine treatment response, and (3) the possibility that selective hypertrophy of striatal structure may be caused by chronic treatment with typical neuroleptics, but not by clozapine.

Atrophy↗
PubMed1994

Clozapine, negative symptoms, and extrapyramidal side effects.

The importance of persistent negative symptoms in schizophrenia as a limiting factor in psychosocial and vocational rehabilitation has been increasingly emphasized. As a result, treatment trials and new drug development programs are focusing more attention on negative symptoms. Unfortunately, there is enormous phenomenological overlap between negative symptoms and neuroleptic-induced parkinsonism. We report data from a cohort of 56 clozapine-treated patients demonstrating significant correlations between measures of akinesia and anergia. Despite an average drug washout of over 2 weeks, the persistence of drug-induced parkinsonism can confound the assessment of therapeutic drug effects on negative symptoms.

Adolescent↗