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Biomedical subjects

D F Levinson

Publications and source records attributed to D F Levinson.

At least 55 records · Page 3Linked to original sources

Defining the schizophrenia spectrum: issues for genetic linkage studies.

Genetic linkage studies of schizophrenia depend on accurate psychiatric diagnosis of relatives within multiply affected families. Each investigator makes a series of explicit or implicit decisions to define which relatives will be assumed to share a schizophrenia-related genotype, that is, who is an "affected relative." In this article we delineate issues that we believe should be considered in such studies and review the relevant literature. Issues include criteria for selecting probands; whether broader criteria should be used to select affected relatives; approaches to including or excluding diagnoses for which family study data suggest a relationship to schizophrenia or to affective disorders or other psychiatric disorders; clarification of diagnostic hierarchy; and issues related to substance abuse and neurological disorders. Also discussed are whether relatives without spectrum diagnoses should be considered unaffected or undiagnosed in linkage analyses, how bilateral familial affectedness should be defined, and provision for independent review of study diagnoses. As an illustration, the clinical model for the authors' schizophrenia linkage study is described.

Genetic Linkage↗

Fluphenazine dose, clinical response, and extrapyramidal symptoms during acute treatment.

Fifty-three patients with acute exacerbations of Research Diagnostic Criteria schizophrenic, schizoaffective (mainly schizophrenic), and other nonaffective psychoses completed 24 or 28 days of treatment with randomized, fixed, double-blind doses of 10, 20, or 30 mg of oral fluphenazine hydrochloride daily. In the sample as a whole, improvement was not predicted by dose but was negatively related to duration of illness and of lifetime hospitalization, and to the presence of akathisia during the study (which was unrelated to chronicity). But among patients showing 40% or greater improvement in positive symptoms, percent improvement was predicted by dose and dose per kilogram of body weight; this was not the case for negative symptoms. Severity of acute extrapyramidal symptoms (excluding acute dystonia, dyskinesia, and akathisia) was significantly correlated with dosage per kilogram. Doses greater than 0.2 mg/kg per day were associated with greater clinical improvement but also with a high incidence of extrapyramidal symptoms; doses over 0.3 mg/kg per day were associated with more severe extrapyramidal symptoms. These preliminary results suggest that there is a linear relationship between fluphenazine dosage and acute outcome, and that this relationship is observed in patients whose conditions improve to a criterion level. It is suggested that the nonresponder group may include many patients in whom dose is not relevant because they are unable (for a variety of reasons) to respond to the study treatment conditions; excluding them from analysis may allow a significant dose-response relationship to be observed. Akathisia deserves further study as a possible predictor of nonresponse.

Acute Disease↗

Prevalence of substance abuse in schizophrenia: demographic and clinical correlates.

Methodological issues involved in assessing the prevalence of substance abuse in schizophrenia are discussed, and previous research in this area is comprehensively reviewed. Many studies suffer from methodological shortcomings, including the lack of diagnostic rigor, adequate sample sizes, and simultaneous assessment of different types of substance abuse (e.g., stimulants, sedatives). In general, the evidence suggests that the prevalence of substance abuse in schizophrenia is comparable to that in the general population, with the possible exceptions of stimulant and hallucinogen abuse, which may be greater in patients with schizophrenia. Data are presented on the association of substance abuse with demographics, diagnosis, history of illness, and symptoms in 149 recently hospitalized DSM-III-R schizophrenic, schizophreniform, and schizoaffective disorder patients. Demographic characteristics were strong predictors of substance abuse, with gender, age, race, and socioeconomic status being most important. Stimulant abusers tended to have their first hospitalization at an earlier age and were more often diagnosed as having schizophrenia, but did not differ in their symptoms from nonabusers. A history of cannabis abuse was related to fewer symptoms and previous hospitalizations, suggesting that more socially competent patients were prone to cannabis use. The findings show that environmental factors may be important determinants of substance abuse among schizophrenic-spectrum patients and that clinical differences related to abuse vary with different types of drugs.

Adolescent↗

Acute dystonia during fixed-dose neuroleptic treatment.

Eighty-six patients with acute psychotic exacerbations were treated with fixed dosage regimens of oral fluphenazine up to 10-30 mg/day in randomized, double-blind studies. Dystonic reactions occurred in 33.8% of the subjects at risk. Of these, 58% occurred by the third day, 88% by the fourth day, and 100% by the ninth day of treatment; most occurred later in the interdose interval. Significant predictors of dystonic reactions were higher fluphenazine mg/kg dosage and younger age. There was a trend toward a lower risk of dystonia in patients who received amobarbital sodium for agitation. Results are discussed in relation to possible mechanisms of neuroleptic-induced dystonia.

Adult↗

Single-dose pharmacokinetics of fluphenazine after fluphenazine decanoate administration.

Fluphenazine decanoate is commonly used as part of maintenance treatment of schizophrenia, but its pharmacokinetics are poorly understood. We administered a single intramuscular dose of fluphenazine decanoate to nine patients and found that plasma fluphenazine level did not decline to 50% of the peak level by day 26 in any of the patients. This means that it has a long half-life measurable in months rather than weeks.

Adult↗

What HMOs should tell their subscribers, and what you can do about it.

All health maintenance organization (HMO) plans try to control costs by restricting choice of physicians and regulating utilization of service. Have some plans gone too far? Patient and physician can become caught in a complex web of gatekeepers and capitation arrangements, withholds, bonuses, and penalties. Patients are almost always unaware of the details of these pressures on the physician. For the free market system to operate, potential subscribers should receive all of the facts about their HMOs. This article offers practical suggestions for concerned physicians, including information about proposals for legislative requirements of disclosure statements and a list of questions patients should ask before joining an HMO.

Economic Competition↗

Exacerbation of panic disorder during propranolol therapy.

Two patients experienced new onset or worsening of panic disorder during treatment with propranolol for tachycardia or palpitations associated with a diagnosis of mitral valve prolapse. Both patients had a family history of panic disorder; one also had a family history of mitral valve prolapse and depression. As antidepressant drugs can treat both depression and panic disorder, it would not be inconsistent that propranolol might exacerbate either disorder. Other possible interpretations of these two cases are discussed.

Adult↗

Schizoaffective mania reconsidered.

Schizoaffective mania refers to a heterogeneous group of disorders characterized by mixtures of schizophrenic and manic (or bipolar) symptoms. Of the proposed diagnostic criteria, the Research Diagnostic Criteria (RDC) most clearly distinguish relevant subgroups. Family, clinical, and treatment studies suggest that the RDC's mainly affective subtype of schizoaffective mania is a variant of psychotic bipolar disorder. Limited available data suggest that the mainly schizophrenic subtype has a poorer prognosis and includes cases more closely related to schizophrenia. Schizoaffective mania also overlaps with proposed categories such as reactive and cycloid psychosis. It is premature to assume that all schizoaffective manic disorder represents a bipolar variant. Further studies that differentiate patients according to subtype, drug response, and course are needed.

Bipolar Disorder↗

Neuroleptic-induced extrapyramidal symptoms with fever. Heterogeneity of the 'neuroleptic malignant syndrome'.

From 39 reported cases of the "neuroleptic malignant syndrome," three groups were identified: those with concurrent medical problems that could cause fever that accompanied the extrapyramidal symptoms; those with medical problems less clearly related to fever; and those without other medical disorders. Dehydration, infection, pulmonary embolus, and rhabdomyolysis were the common complications of untreated extrapyramidal symptoms. Three patients died, all with medical complications. In 14 cases, no medical cause of fever was identified. Hypotheses about mechanisms for fever include psychiatric illness, disruption of dopaminergic aspects of thermoregulation, and peripheral and central effects on muscle contraction leading to excess heat production. Neuroleptic-induced rigidity should be treated vigorously, with prompt discontinuation of neuroleptic therapy and administration of dopamine agonists in severe cases with or without fever. The cases of extrapyramidal symptoms with fever are too heterogeneous to justify the assumption of a unitary and "malignant" syndrome.

Adolescent↗

The skin conductance orienting response in neuroleptic-free schizophrenics: replication of the scoring criteria effect.

It has been suggested that the use of invalid scoring criteria might be responsible for the finding of excessive nonhabituation of the skin conductance orienting response (SCOR) in schizophrenia. Certain criteria may confuse SCOR and spontaneous SC activity in subjects with high rates of the latter (Levinson et al. 1984). To replicate this finding, data were reanalyzed from a study of 25 neuroleptic-free schizophrenic patients and 23 normal male subjects. Analysis of response latency and amplitude during a habituation paradigm of 11 78.5-dB tones confirmed the predictions. Broad scoring criteria (SCOR onset 1-5 sec poststimulus, and a three-no-response-trials habituation criterion) produced significantly different habituation scores than more restrictive criteria (1.6-3.0 sec latency window and a two-trials habituation criterion). Nonhabituation was scored in five patients and six normals by the former criteria, but in no patient and one normal by the latter. Nonhabituators, defined by using the broad criteria, had higher rates of spontaneous activity. The narrow latency window contained significantly more responses than could be explained by the spontaneous activity rate, but this was not true for the added time permitted by the broad window. It is concluded that the use of more restrictive scoring criteria may help to clarify the validity of SCOR nonresponse or hyporesponse as a marker for a type of schizophrenic illness.

Acoustic Stimulation↗

The orienting response in schizophrenia: proposed resolution of a controversy.

The habituation of the skin conductance orienting response ( SCOR ) was studied in 36 schizophrenic and 11 normal male subjects. Scoring criteria significantly influenced results: more inclusive criteria (used in most SCOR studies) scored 56% of patients as nonresponders and 19% as slow habituators . More restrictive criteria scored 75% of patients as nonresponders, and the remainder as faster habituators than normals. The faster habituation of patient responders could be explained by the effects of low response amplitude. Evidence is given for the greater validity of the restrictive scoring criteria; on this basis the schizophrenic patients in this study were SCOR nonresponders or fast habituators . The data suggest that the more inclusive scoring criteria can confuse spontaneous and orienting activity. Clinical and theoretical implications are discussed.

Acoustic Stimulation↗