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M A Weiler

Publications and source records attributed to M A Weiler.

16 recordsLinked to original sources
PubMed2001

Long-term outcome of patients who receive ketamine during research.

BACKGROUND: To comprehend the pathophysiology of schizophrenia and to facilitate drug discovery, animal and human models of schizophrenia are necessary. Ketamine, a noncompetitive N-methyl-D-aspartate antagonist, has been used to probe glutamatergic function in normal and schizophrenic volunteers. These studies and others have provided data consistent with a putative involvement of a glutamatergic dysfunction in the pathophysiology of schizophrenia; however, these studies have also raised concerns about the distress inflicted on patients, the potential for adverse events, and the serious long-term effects that could possibly be induced by symptom-simulating action. METHODS: For all patient volunteers (n = 30) who participated in these studies, we reviewed the acute safety during and in the immediate postketamine administration. Patients available for long-term follow-up (n = 25) were matched to a group of patients (n = 25) who participated in research but did not receive ketamine. We compared their long-term outcome in terms of psychopathology, the need for psychiatric care, and the amount of antipsychotic medication required for optimal therapeutic response. RESULTS: There were no serious adverse events in more than 90 ketamine interviews. Distress to patients was minimal, which is shown by the lack of anxiety ratings. Over a mean follow-up period of 8 months, we found no differences between patients who did and did not receive ketamine on any measures of psychopathology, psychiatric care, or the amount of antipsychotic medication. CONCLUSIONS: In a controlled environment and paying close attention to subject safety features, administering subanesthetic doses of ketamine causes no adverse events and little distress to schizophrenic volunteers. This study strongly indicates that administering ketamine does not change any aspect of the course of schizophrenic illness.

Adult↗
PubMed2001

Effects of ketamine in normal and schizophrenic volunteers.

This study evaluates the effects of ketamine on healthy and schizophrenic volunteers (SVs) in an effort to define the detailed behavioral effects of the drug in a psychosis model. We compared the effects of ketamine on normal and SVs to establish the comparability of their responses and the extent to which normal subjects might be used experimentally as a model. Eighteen normal volunteers (NVs) and 17 SVs participated in ketamine interviews. Some (n = 7 NVs; n = 9 SVs) had four sessions with a 0.1-0.5 mg/kg of ketamine and a placebo; others (n = 11 NVs; n = 8 SVs) had two sessions with one dose of ketamine (0.3 mg/kg) and a placebo. Experienced research clinicians used the BPRS to assess any change in mental status over time and documented the specifics in a timely way. In both volunteer groups, ketamine induced a dose-related, short (<30 min) increase in psychotic symptoms. The scores of NVs increased on both the Brief Psychiatric Rating Scale (BPRS) psychosis subscale (p =.0001) and the BPRS withdrawal subscale (p =.0001), whereas SVs experienced an increase only in positive symptoms (p =.0001). Seventy percent of the patients reported an increase (i.e., exacerbation) of previously experienced positive symptoms. Normal and schizophrenic groups differed only on the BPRS withdrawal score. The magnitude of ketamine-induced changes in positive symptoms was similar, although the psychosis baseline differed, and the dose-response profiles over time were superimposable across the two populations. The similarity between ketamine-induced symptoms in SVs and their own positive symptoms suggests that ketamine provides a unique model of psychosis in human volunteers. The data suggest that the phencyclidine (PCP) model of schizophrenia maybe a more valid human psychosis/schizophrenia drug model than the amphetamine model, with a broader range of psychotic symptoms. This study indicates that NVs could be used for many informative experimental psychosis studies involving ketamine interviews.

Adult↗
PubMed2001

Abnormal patterns of regional cerebral blood flow in schizophrenia with primary negative symptoms during an effortful auditory recognition task.

OBJECTIVE: Using functional brain imaging, the authors sought to replicate their earlier finding of low metabolism in the middle frontal and inferior parietal cortices of schizophrenic patients with primary negative symptoms. METHOD: According to the presence or absence of enduring negative symptoms, patients with schizophrenia were classified as having deficit or nondeficit schizophrenia, respectively. Twelve normal volunteers and 18 drug-free schizophrenic volunteers (deficit, N=8; nondeficit, N=10) were trained in a tone discrimination task. They were trained to perform with 70%-80% accuracy and were then scanned with positron emission tomography with [(15)O]H(2)O during three conditions: rest, sensory-motor control task, and decision task. RESULTS: Levels of performance of the auditory recognition task were similar in the three groups. An initial hypothesis-driven analysis revealed that across tasks the deficit group failed to show significant activation in the middle frontal cortex. This was in contrast to both the normal volunteers and nondeficit patients. When the patient groups were contrasted, the deficit patients showed significantly less activation in the middle frontal cortex bilaterally during the control task and in the right middle frontal cortex and inferior parietal cortex during the decision task. An exploratory analysis contrasting deficit and nondeficit patients across conditions did not reveal further differences between groups. CONCLUSIONS: This study replicated the finding of low activation in the middle frontal cortex and inferior parietal cortex in deficit schizophrenia. This deficit was observed without performance confound and may provide a marker of primary negative symptoms and a target for new therapies.

Adult↗
PubMed2000

Insight and symptom change in schizophrenia and other disorders.

OBJECTIVE: This study sought to evaluate levels of insight and change in insight in subjects with schizophrenia and other major psychiatric disorders. This study also evaluated the relationship of insight to acute psychopathology. METHOD: One-hundred and eighty-seven subjects consecutively admitted to an acute care psychiatric unit and who met DSM-III-R criteria were evaluated by the Insight and Treatment Attitudes Questionnaire and Brief Psychiatric Rating Scale on admission and discharge. Relationships of insight to diagnosis, involuntary commitment status and change in insight were evaluated with analysis of variance and post hoc Tukey's Standardized Range test. Relationships of change in insight and symptoms were evaluated with analysis of covariance (ANCOVA) and correlation. RESULTS: Insight deficits were more prevalent in schizophrenia, a mixed group of other psychosis and bipolar disorder as compared with major depressive and schizoaffective disorder. Committed patients had lower insight. Insight improved across diagnoses during hospital care in both voluntary and committed patients. Significant relationships between improved symptoms and improved insight were obtained in the bipolar, schizophrenia and major depressive groups. CONCLUSION: Insight deficits are prevalent in schizophrenia and bipolar disorder. Many patients show improved insight as their acute symptoms improve. Some aspects of insight are state related during exacerbation of illness in patients with schizophrenia and bipolar disorder.

Acute Disease↗
PubMed2000

Ketamine effects on eye movements.

In order to determine if the N-methyl-D-aspartate antagonist ketamine would reproduce eye movement dysfunction in schizophrenia, we studied 12 normal control subjects with low dose (0.1 mg/kg) bolus injection of ketamine in a double-blind placebo-controlled study. Oculomotor measures were obtained during smooth pursuit that included closed loop gain and measures of gain during masking conditions. Measures during initiation of smooth pursuit included latency, open loop acceleration and velocity. Ketamine disrupted closed loop gain and open loop acceleration but not measures during the masking conditions. The ketamine partly reproduced some abnormalities seen in schizophrenia but not measures that may be more specifically linked to familial abnormalities found in family members of subjects with schizophrenia.

Adult↗
PubMed1998

Antipsychotic properties of the partial dopamine agonist (-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine(preclamol) in schizophrenia.

BACKGROUND: In an ongoing effort to characterize the clinical pharmacologic profile of the partial dopamine agonist (-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine [(-)-3PPP], we administered it to drug-free schizophrenic patients in two consecutive studies. METHODS: In a preliminary dose-finding study, 9 patients were treated using a 6-week placebo-controlled crossover design. Then, to properly demonstrate the antipsychotic effect, we carried out an early efficacy study; here 10 patients received (-)-3PPP, 300 mg B.I.D., in a 1-week placebo-controlled crossover study. RESULTS: Dose-Finding Study: (-)-3PPP showed apparent antipsychotic effect in repeated dosing, with 300 mg B.I.D. being the most effective dose for antipsychotic action; however, the apparent antipsychotic action was not sustained for longer than 1 week, presumably because of desensitization of the receptor by the agonist. Early Efficacy Study: Positive symptoms as measured by the Psychosis Change Scale decreased in 1 week by 30% with (-)-3PPP compared to placebo, and negative symptoms measured with the Brief Psychiatric Rating Scale Withdrawal subscale decreased by 28% with the drug. In both studies, (-)-3PPP lacked any evidence of motor side effects. CONCLUSIONS: These data show that psychotic symptoms decrease with (-)-3PPP and suggest that the treatment of schizophrenia with partial dopamine agonist is a promising strategy. Future attention will be directed toward testing techniques to diminish the tachyphylaxis to allow an ongoing therapeutic effect.

Adult↗
PubMed1988

EEG sleep, lithium transport, dexamethasone suppression, and monoamine oxidase activity in borderline personality disorder.

Twenty-one patients who met DSM-III criteria for borderline personality disorder (BPD) and also scored at least 7 on the Diagnostic Interview for Borderlines (DIB) were assessed on four biological markers: electroencephalographic (EEG) sleep, in vitro lithium ratio, platelet monoamine oxidase (MAO), and dexamethasone suppression test (DST). REM latency averaged 58.66 (SD 14.39); platelet MAO averaged 21.74 (SD 10.33); and lithium ratio was 0.357 (SD 0.139) in the BPD patients. All of those values were significantly abnormal. Many patients had abnormalities on three or four measures. These patients in general had multiple Axis I diagnoses from the Diagnostic Interview Schedule (DIS), and these Axis I diagnoses tended to produce patient clusters. Patients with a DIS diagnosis of schizophrenia, mania, hypomania, or schizoaffective mania had elevated lithium, low MAO, and normal EEG sleep, while those patients with coexisting major depression tended to have short rapid eye movement (REM) latency, high REM density, and normal MAO and lithium ratio. Only two patients were nonsuppressors on the DST, confirming recent reports of normal DST results in personality disorders.

Adult↗
PubMed1987

Interpretation of negative transference in nonanalytic settings.

This article presents a technique and attitude for dealing with problem or difficult patients, utilizing concepts generated from psychoanalysis for use in settings or contexts that are nonpsychoanalytic. The concepts of transference, counter-transference, resistance, and interpretation of transference are defined for use in nonanalytic contexts. The process of formulation of interpretations, and modes of patient response in nonanalytic contexts are discussed and illustrated with clinical examples. The possible benefits and limitations of this way of relating to problem patients are also discussed from clinical and theoretical perspectives.

Adult↗
PubMed1986

4 p.m. baseline cortisol level as a predictor of DST results in depression.

To assess the relationship of baseline cortisol to the 1 mg dexamethasone suppression test (DST), 4 p.m. baseline and 4 p.m. postdexamethasone blood samples were drawn on 52 consecutive depressed outpatients. Baseline cortisol correlated significantly with post-DST values, and baseline levels above 15 micrograms/dl predicted DST nonsuppression with 90.4% accuracy. These data lend some support to the usefulness of baseline cortisol determination in depressed outpatients in whom a full DST may be difficult.

Ambulatory Care↗
PubMedDate not supplied

Explorations in the relationship of dream sleep to schizophrenia using positron emission tomography.

This study explored the relationship between rapid eye movement (REM) sleep and schizophrenia using positron emission tomography. Glucose use was compared between 49 schizophrenics, 30 awake controls and 12 controls in REM sleep. Assessment of the frequency and locations of brain areas showing significant differences suggested that REM did not resemble schizophrenia. Schizophrenics were between the higher awake controls and lower REM controls in corpus callosum glucose use. Hallucinating schizophrenics showed lower left caudate glucose use.

Adult↗