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Biomedical subjects

J P Docherty

Publications and source records attributed to J P Docherty.

At least 55 records · Page 3Linked to original sources
PubMed1982

Long-term pimozide pretreatment differentially affects behavioral responses to dextroamphetamine in schizophrenia. Further exploration of the dopamine hypothesis of schizophrenia.

In ten of 30 schizophrenic patients treated with pimozide for five weeks, 20 mg of dextroamphetamine sulfate induced an increase in psychosis. The number of patients becoming more psychotic with the dextroamphetamine challenge was not significantly different from the number who worsened after dextroamphetamine challenge when pretreated with placebo. Half of the patients who showed a psychotic response to dextroamphetamine during placebo pretreatment responded to dextroamphetamine with an increase in psychosis after pimozide treatment. Dextroamphetamine induced a worsening in patients who had improved with pimozide. The stability of the preinfusion condition is more important to the type of response to dextroamphetamine than long-term pretreatment with a dopamine receptor blocker. The activation-euphoria response to dextroamphetamine was unaffected by pimozide pretreatment, which suggests that the changes in psychosis and activation may be regulated by different mechanisms. These findings question the postulated relationship between the antipsychotic drug response and dopamine receptor blockade.

Adolescent↗
PubMed1982

d-Amphetamine-induced heterogeneous changes in psychotic behavior in schizophrenia.

In this placebo-paired, double-blind study, 13 of 45 schizophrenic patients showed an acute improvement in schizophrenic symptoms following d-amphetamine infusion (20 mg). The 18 patients who worsened tended to have higher CSF 3-methoxy-4-hydroxyphenylglycol levels than did those who improved. d-Amphetamine blood levels and clinical descriptors of schizophrenic subgroups did not differentiate patients who improved from those who worsened; however, patients who improved had been significantly more psychotic before the infusion. Patients who worsened had been more psychotic than those who did not change. The authors suggest that those who did not change. The authors suggest that sensitivity to dopamine stimulation in schizophrenia is state-dependent rather than trait-dependent and that the simple, undirectional hypothesis of schizophrenia needs to be reformulated.

Adolescent↗
PubMed1982

Prediction of early relapse after pimozide discontinuation by response to d-amphetamine during pimozide treatment.

Thirteen schizophrenic patients underwent a d-amphetamine infusion while being treated with pimozide, an antipsychotic agent and a relatively specific dopamine (DA) blocker. Six patients who showed an acute increase in psychosis with d-amphetamine relapsed within 3 months after pimozide withdrawal. Of the seven patients who did not change in psychosis with d-amphetamine, six did not relapse after pimozide discontinuation (Fisher's exact test, p less than 0.005). Retrospectively, the psychosis-inducing effects of d-amphetamine were found to be predictive of psychotic exacerbation following subsequent pimozide withdrawal. Pimozide failed to block the psychotogenic effects of d-amphetamine in six patients indicating that other mechanisms besides DA may play a role in psychotic decompensation. The d-amphetamine infusion paradigm should be studied further to determine its clinical value for identifying which schizophrenic patients are at risk for relapse after discontinuation of neuroleptic treatment.

Acute Disease↗
PubMed1981

Acute amphetamine response predicts antidepressant and antipsychotic responses to lithium carbonate in schizophrenic patients.

Acute behavioral changes following a 20 mg i.v. d-amphetamine predicted the small antipsychotic and antidepressant effects of the third week of lithium treatment in schizophrenic patients. Multivariate regression models accounted for 95% of the variance predicting the antipsychotic effects and for 89% of the variance predicting the antidepressant effects in postpsychotic depressed patients. The greater the increases in the d-amphetamine-induced changes in the thought disorder cluster of the Brief Psychiatric Rating Scale, the greater the antipsychotic effects of lithium. The data suggest that the modest behavioral changes observed with lithium in schizophrenia are most likely drug-induced.

Acute Disease↗
PubMed1981

Dopamine receptor supersensitivity and schizophrenia: a review.

Advances in knowledge of brain neurochemistry have lent impetus to the biological study of schizophrenia. A prominent example is the dopamine hypothesis. Increasing additions to and refinements of neurochemical knowledge, particularly the study of receptors, have continued to support biological hypotheses of schizophrenia. A recently proposed hypothesis is that schizophrenic patients suffer from dopamine receptor supersensitivity at certain phases of their illness. The present article selectively reviews data that are relevant to this refinement of the dopamine hypothesis.

Adenylyl Cyclases↗
PubMed1981

Trends in emergency psychiatry in the last two decades.

Emergency psychiatric services provide essential care. Their utilization may also be assumed to reflect the health care needs of a population. The authors observed trends in an emergency psychiatric service over a 17-year period by comparing 400 randomly selected patient visits in 1977 with date from 1960 and 1970. They found a decrease in the number of patients seeking treatment, decreased patient age and socioeconomic status, increased use by men, increased night visits, little change in diagnostic categories, and a striking increase in hospitalization since 1970. These data support the importance of assessing trends in emergency psychiatric services over time to ensure that they meet the needs of the population being served.

Adult↗
PubMed1980

Lack of behavioral supersensitivity to d-amphetamine after pimozide withdrawal. A trial with schizophrenic patients.

The dopamine hypothesis of schizophrenia claims that increased dopamine activity underlies psychotic behavior. This hypothesis gets major support from the reported d-amphetamine-induced worsening of psychosis, because amphetamine increases dopamine activity in the brain. Dopamine receptor supersensitivity has been shown to be present in animals during the postneuroleptic period. In this study the postulated relationships between psychotic decompensation as observed after d-amphetamine infusion and the dopamine receptor supersensitivity expected to be present during the neuroleptic withdrawal period were examined. Twenty milligrams of d-amphetamine administered intravenously did not cause a stronger psychotogenic effect in 12 schizophrenic patients. One week after discontinuation of pimozide treatment, the d-amphetamine-induced change as indicated by the Brief Psychiatric Rating Scale (BPRS) paranoid disturbance cluster score, was not significantly different from the response to a similar infusion during the drug-free state. Unexpectedly, the increase in the BPRS mannerisms and posturing item and in the pulse rate response to d-amphetamine were decreased. These results raise questions about the role of dopamine in d-amphetamine effects and suggest postneuroleptic dopamine receptor subsensitivity. They challenge a simple dopamine hypothesis of schizophrenia.

Adolescent↗
PubMed1980

Platelet MAO and amitriptyline treatment.

Some tricyclic antidepressants have been reported to inhibit monoamine oxidase (MAO) activity in vitro in addition to blocking the reuptake of norepinephrine and/or serotonin. While the inhibition of MAO is reversible, platelet MAO activity in depressed patients responding to amitriptyline treatment has been reported to be reduced after drug treatment. In a reverse design, we measured platelet MAO activity and drug levels in patients chronically being treated with amitriptyline and again 2 and 4 weeks after stopping the medication. Although tricyclic drug concentrations were initially within the therapeutic range and undetectable on placebo treatment, platelet MAO activities were unchanged.

Amitriptyline↗
PubMed1980

Effects of dopamine blockade on gonadotropins and testosterone in men.

The authors found that plasma luteinizing hormone (LH), prolactin, and testosterone were initially normal in nine acutely psychotic males with schizophrenia or schizo-affective disorder; follicle-stimulating hormone (FSH) was normal in eight of the nine. When patients were treated with pimozide, a relatively specific dopamine receptor blocker, there were statistically significant declines in FSH and LH, although levels remained within normal limits. Prolactin rose significantly, but testosterone did not change. The observed reductions in FSH and LH concentrations are consistent with the hypotheses that dopamine and/or prolactin play a role in gonadotropin secretion. The maintenance of normal levels of gonadotropins and testosterone, however, suggests that these patients possessed relatively normal hypothalamic-pituitary-gonadal axis function before and during a course of neuroleptic treatment.

Adult↗
PubMed1979

Predicting drug-free improvement in schizophrenic psychosis.

In a sample of 22 psychotic schizophrenic patients, eight improved substantially during a 30-day drug-free period. The drug-free improver group differed from the nonimprover group in demonstrating a later age of onset, briefer psychotic episodes, shorter hospitalizations, and better prognostic scores on the Phillips Scale, Strauss-Carpenter Modified Prognostic Scale, and the Vaillant Scale. After drug withdrawal, drug-free improvers frequently demonstrated further improvement when treated with doses of neuroleptic drugs that were substantially lower than the clinically recommended doses. The authors raise the question as to whether the drug-free improvers may represent a subgroup of schizophrenic patients who are being overtreated presently by standard neuroleptic practice.

Adolescent↗
PubMed1979

Subtypes of schizophrenia: descriptive models.

Descriptive approaches to subtyping schizophrenia use symptoms, signs, and functioning characteristics as diagnostic criteria. Such approaches often appear superficially to be obvious, simple, and atheoretical; in reality, however, there are many ways in which descriptive data can be selected and organized to subtype patients. This report describes these various approaches. Selection of diagnostic criteria can focus primarily either on cross-sectional or longitudinal characteristics of patients. Alternative ways of organizing descriptive data include typological and dimensional approaches and two increasingly common complex models, multiaxial and hierarchical subtyping. Examples and implications of these alternative approaches are described, and methods for choosing among them are suggested.

Cross-Sectional Studies↗
PubMed1979

Psychological factors in the prognosis of malignant melanoma: a prospective study.

Sixty-four patients with Stage I or II malignant melanoma who were apparently disease free rated the amount of adjustment needed to cope with their illness on a scale of 1 to 100. The resultant figure was called the melanoma adjustment score. Twenty-nine patients who relapsed within 1 year of surgery reported a score of 53 +/- 31 (mean +/- SD); 35 nonrelapsers reported a score of 80 +/- 20, p less than 0.001. Based upon analysis of indivual melanoma adjustment scores in the first 31 patients, we predicted that subjects scoring greater or equal to 65 would stay in remission, whereas those scoring greater than 65 would relapse. Applying this prospectively to the next 33 patients we correctly identified 25 of 33 outcomes (76%), p less than 0.03. This psychological variable was independent of known biological prognostic factors, which did not predict 1 year survival. The melanoma adjustment score was also independent of the number of positive lymph nodes, which did correlate with outcome in these patients. The results suggest a role for psychological factors in the one year prognosis of this malignancy.

Adolescent↗
PubMed1979

Intrapsychic structural effects of psychiatric research.

The authors observed that many psychotic patients on a clinical/research ward incorporated various aspects of research organization into their own evolving intrapsychic structures. This process had either beneficial or deleterious clinical effects, depending on the attributes of the research and the specific mental functions to which these attributes became attached. The observations resulted in the development of a set of recommendations for maximizing the therapeutic usefulness of this phenomenon and minimizing its countertherapeutic drawbacks.

Adaptation, Psychological↗