The clinical features of patients who satisfy a variety of criteria for the negative syndrome can be arranged in five groups of phenomena: (a) poverty of thought and speech, (b) blunted affect, (c) decreased motor activity, (d) apathy and abolition, and (e) diminished interpersonal interaction. We have shown that depressed mood and depressive cognition are not related to the negative syndrome, but there is some overlap between the specific phenomena of depressive illness and negative symptoms in schizophrenia. Items measuring cognitive impairment have a moderate correlation with the negative syndrome, but the negative syndrome accounts for less than half of the variance of cognitive performance. These items that define the negative syndrome can be as reliably measured as depressive and positive symptoms.
A very large number of therapeutic trials of antidepressant drugs have been reported in the scientific literature. Until now, the comparison of one drug with another, or with placebo, has been performed typically by comparing the scores on depression rating scales of the two groups of patients at fixed points of time after the beginning of therapy. It was postulated in 1989 that the curves of the recovery scores followed an exponential curve of the formula y = ae-bx + c. This hypothesis was tested in a double-blind controlled trial of the antidepressant minaprine, with the use of the scores on the Hamilton Rating Scale for Depression (HAM-D). We found that the correlation coefficient, Pearson's r, between the log of the HAM-D value and the week number of the study was -0.99. This gives a coefficient of determination of 0.98, which makes it clear that the model adequately fits the data. We conclude that the use of the formula gives a method of testing the statistical significance of the difference between treatments as a valuable alternative to traditional tests. We believe that this would give a much more sensitive discrimination between treatments because all of the data points are used to calculate a single parameter--the slope of the curve.
Investigation of the relationships between negative schizophrenic symptoms, abnormal involuntary movements and age in 179 chronic schizophrenic patients confirmed that both orofacial and trunk and limb dyskinesia are associated with negative symptoms, but only orofacial dyskinesia showed a significant increase in prevalence with increasing age. Estimation of the mean age of onset of orofacial dyskinesia from the observed variation in prevalence of orofacial dyskinesia with age indicated that patients having negative symptoms tend to develop orofacial dyskinesia at an earlier age. The estimated mean age of onset was 43.6 years in patients with substantial negative symptoms, and 54.6 years in patients without substantial negative symptoms. These findings support the proposal that the pathological process underlying negative symptoms can contribute to the occurrence of both orofacial and trunk and limb dyskinesia, but, in the case of orofacial dyskinesia, there is a synergistic interaction between the pathological process underlying negative symptoms and age-related neuronal changes.
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