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Profiles of the pharmacologic response of positive and negative symptoms in schizophrenia

Published online by Cambridge University Press:  28 April 2020

D. Pickar ,
A. Breier ,
O.M. Wolkowitz  and
C. Pato
D. Pickar*
Affiliation:
Section on Clinical Studies, Clinical Neuroscience Branch, National Institute of Mental Health, BLDG 10, RM 4N212, 9000 Rockville Pike, Bethesda, MD20892
A. Breier
Affiliation:
Section on Clinical Studies, Clinical Neuroscience Branch, National Institute of Mental Health, BLDG 10, RM 4N212, 9000 Rockville Pike, Bethesda, MD20892
O.M. Wolkowitz
Affiliation:
University of California (San Francisco), Dept Psychiatry, San Francisco, CA
C. Pato
Affiliation:
Section on Clinical Studies, Clinical Neuroscience Branch, National Institute of Mental Health, BLDG 10, RM 4N212, 9000 Rockville Pike, Bethesda, MD20892
*
Corresponding author: Correspondance à adresser à: David Pickar, M.D. Chief, Section on Clinical Studies, Clinical Neuroscience Branch, NIMH, NIH Bldg 10, Rm 4N212, 9000 Rockville Pike, Bethesda, MD 20892 (USA)
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Summary

The delineation of the symptoms of schizophrenia into positive and negative types has been an important trend in psychiatric research over the past decade. This approach reflects renewed interests in clinical description and in developing etiologic hypotheses. The responsivity of positive and negative symptoms to neuroleptic and other pharmacotherapies, an issue of considerable clinical and research importance, however, remain in controversy.

We have observed that double-blind fluphenazine administration to 19 schizophrenic inpatients who had been maintained free from neuroleptic treatment for an extended period of time resulted in significant decreases in both positive as well as negative symptoms. The time course of symptom change differed, however, and the change in symptoms was not correlated, suggesting that the underlying pathophysiologies of positive and negative symptoms are only partially overlapping. The relative balance between positive and negative symptoms in individual patients, a putative schizophrenia trait characteristic, was found to be significantly altered by neuroleptic treatment, raising questions about the reliability of this classification approach.

In longitudinal studies in which plasma levels of the dopamine metabolite, homovanillic acid (HVA), were measured, change in negative symptoms associated with neuroleptic withdrawal and treatment were correlated, respectively, with changes in levels of plasma HVA. These data further support a relationship between negative symptoms and dopaminergic function. In addition to neuroleptic-induced reductions in negative symptoms, the augmentation of neuroleptic antipsychotic effects by the triazolobenzodiazepine, alprazolam, includes improvement in negative and positive symptoms in responsive patients.

These data including longitudinal studies of individual patients suggest that negative as well as positive symptoms respond to pharmacologic intervention. The clinical and research implications of these findings are discussed.

Résumé

Résumé

La division des symptômes de la schizophrénie en deux types, positif et négatif, a été un aspect important de la recherche en psychiatrie ces dernières années. Cette approche est le reflet d'intérêts nouveaux dans la description clinique et le développement d’hypothèses étiologiques. La réponse des symptômes positifs et négatifs aux neuroleptiques et autres thérapeutiques pharmacologiques, d’importance considérable sur le plan clinique et de la recherche, reste cependant controversée.

Nous avons observé que l'administration en double aveugle de fluphênazine à 19 schizophrènes hospitalisés, non soumis à un traitement aux neuroleptiques pendant une longue période, a induit une diminution significative des symptômes aussi bien positifs que négatifs. L’évolution des symptômes était cependant variable, et les symptômes n’étaient pas corrélés entre eux, suggérant que les pathophysiologies sous-jacentes ne se recoupent que partiellement. L’équilibre relatif entre symptômes positifs et négatifs chez chaque sujet pris individuellement, qui était une caractéristique possible du type de schizophrénie, s’est révélée significativement modifiée par le traitement neuroleptique, mettant en question la fiabilité de cette classification.

Les études longitudinales des taux plasmatiques du métabolite de la dopamine, l’acide homovanillique (HVA), indiquent que les modifications des symptômes négatifs associés au traitement neuroleptique ou à son arrêt sont corrélés avec les variations des taux d'HVA plasmatique. Ces données sont en faveur d'une relation entre les symptômes négatifs et la fonction dopaminergique. La réduction des symptômes négatifs induite par les neuroleptiques jointe à l'augmentation des effets antipsychotiques des neuroleptiques par la triazolobenzodiazépine, l’alprazolam, améliore les symptômes négatifs et les symptômes positifs chez les patients répondeurs.

Ces résultats, en particulier les études longitudinales chez des patients individuels, suggèrent que les symptômes, tant négatifs que positifs, répondent à la pharmacologie. Les implications sur le plan clinique et de la recherche sont discutées.

Keywords

Negative symptomsPositive symptomsSchizophreniaDopamineNeurolepticsAlprazolamSymptômes déficitairesSymptômes productifsSchizophrénieDopamineNeuroleptiquesAlprazolam
Type
Research Article
Information
Psychiatry and Psychobiology , Volume 2 , Issue 4 , 1987 , pp. 277 - 287
Copyright
Copyright © European Psychiatric Association 1987

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