Faculty Bibliography

Reviews studies that have used response to the serotonergic challenge probe metachlorophenylpiperazine (m-CPP) to investigate central serotonin (5-hydroxytryptamine [5-HT]) receptor sensitivity and treatment response prediction in schizophrenia. Results concerning hormonal and other physiologic effects, behavioral effects, and the heterogeneity of behavioral and hormonal responses in m-CPP challenge studies are discussed as well as the blockade of m-CPP response by clozapine and the limitations of the m-CPP paradigm.

Reviews research by the author and others on the Positive and Negative Syndrome Scale (P

In order to examine the effect of neuroleptic medication on the factor structure of schizophrenic symptomatology, 517 DSM-III-R schizophrenic in-patients enrolled in a multicenter phase II drug study were evaluated on their pre-existing neuroleptic at screening on the Positive and Negative Syndrome Scale (PANSS) and after a one-week drug-free period. Separate principal components analyses of the PANSS were done at each time point. PANSS total and component scores were assessed for differences utilizing paired t-tests. Both factor analyses confirmed the five factor model (negative, positive, cognitive, excitement and depression components) explaining 51.7 and 56.2% of the variances at each time point. After medication wash-out psychopathology significantly worsened as measured by total PANSS score and by each of the components. The overall worsening of component scores appeared global and uniform, as evidenced by the fact that at washout, the proportion of individual component scores to total psychopathology remained constant for most components. The lack of change of most components in proportion to the psychopathology total is evidence for the stability of these individual psychopathological dimensions of patients while on and off neuroleptics. The results further support the validity of the five-factor model of schizophrenic psychopathology as measured by the PANSS.

Negative symptoms in schizophrenia comprise a psychopathologic and pathophysiologic syndrome which is absent from normal mental function. Renewed interest in negative symptoms has led to the development of better measuring instruments, among which is the Positive And Negative Syndrome Scale (PANSS), which provides a way of measuring and reporting positive and negative symptoms in a balanced and convenient form. A number of strategies are being investigated for treating negative symptoms. Dopamine agonists such as levodopa, amphetamines and bromocriptine have been shown to produce improvements in negative symptoms, although good, well-controlled clinical trials are lacking. Partial dopamine agonists, such as MAR 327, are also currently under investigation and results are expected soon. Tricyclic, selective serotonin reuptake inhibitors and monoamine oxidase antidepressants appear to be able to modify negative symptoms in schizophrenia, although, once again, carefully designed trials are needed. Modification of GABAergic transmission has shown little promise, but the use of glycine to augment transmission at N-methyl-D-aspartate (NMDA) synapses suggests that the strategy may be beneficial. These results also imply that altered glutamate receptor function may be partly responsible for negative symptoms. One strategy that has been shown to have a beneficial effect against negative symptoms is combined serotonin/dopamine antagonism. Clozapine was found to have this profile after its introduction, and the recently introduced antipsychotic, risperidone was developed intentionally to be a combined 5-HT2/D2 antagonist. Both risperidone and clozapine have been shown to be effective against negative symptoms. One problem associated with the assessment of drug effects on negative symptoms, however, is that drugs can act on both primary and secondary negative symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Schizophrenic psychopathology is heterogeneous and multidimensional. One of the more fruitful strategies to investigate more homogenous domains of psychopathology has been the positive-negative syndrome approach. However, this approach is unable to address a number of important issues. Most schizophrenics present a mixed syndrome; the criteria for what constitutes a positive and negative syndrome are variable; distinguishing primary from secondary negative symptoms can be difficult. In order to address some of these problems, we propose the introduction of a 5-syndrome model based on a reanalysis of factor-analytic procedures used on 240 schizophrenics assessed with the Positive and Negative Syndrome Scale: A negative, positive, excitement, cognitive and depression/anxiety factor. This 5-factor solution is supported by 4 independent and comparable factor analyses. Data on internal consistency of the 5 factors and on initial validation using demographic and clinical variables are presented

Schizophrenic psychopathology is heterogeneous and multidimensional. Various strategies have been developed over the past several years to assess and measure more accurately discrete domains of psychopathology. One of the more fruitful strategies to investigate more homogenous domains of psychopathology has been the positive-negative syndrome approach. However, this approach is unable to address a number of important issues. Most schizophrenics present a mixed syndrome; the criteria for what constitutes a positive and negative syndrome are variable; distinguishing primary from secondary negative symptoms can be difficult. In order to address some of these problems, we propose the introduction of a five-syndrome model based on a reanalysis of factor analytic procedures used on 240 schizophrenics assessed with the Positive and Negative Syndrome Scale. We present data on a five-factor solution that appears to best fit the psychopathological data and that is supported by three independent and comparable factor analyses; negative, positive, excitement, cognitive, and depression/anxiety domains of psychopathology give patients their individual mark. Data on internal consistency of the five factors and on initial validation using demographic and clinical variables are presented.