Christian Scharfetter

Metabolic hyperfrontality and psychopathology in the ketamine model of psychosis using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG)

To date, the ketamine/PCP model of psychosis has been proposed to be one of the best pharmacological models to mimic schizophrenic psychosis in healthy volunteers, since ketamine can induce both positive and negative symptoms of schizophrenia. At subanesthetic doses, ketamine has been reported to primarily block N-methyl-D-aspartate (NMDA) receptor complex giving support to a glutamate deficiency hypothesis in schizophrenia. Positron emission tomography was used to study ketamine-induced psychotic symptom formation in relation to cerebral metabolic alterations in healthy volunteers. Our study shows that NMDA receptor blockade results in a hyperfrontal metabolic pattern. Increased metabolic activity in the frontomedial and anterior cingulate cortex correlated positively with psychotic symptom formation, in particular with ego pathology. Analysis of correlations between syndrome scores and metabolic rate of glucose (CMRglu) or metabolic gradients (ratios) revealed that each psychopathological syndrome was associated with a number of metabolic alterations in cortical and subcortical brain regions, suggesting that not a single brain region, but distributed neuronal networks are involved in acute psychotic symptom formation.

Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis

The effects of the indolehallucinogen psilocybin, a mixed 5-HT2 and 5-HT1 agonist, on regional cerebral glucose metabolism were investigated in 10 healthy volunteers with PET and [F-18]-fluorodeoxyglucose (FDG) prior to and following a 15- or 20-mg dose of psilocybin.Psychotomimetic doses of psilocybin were found to produce a global increase in cerebral metabolic rate of glucose (CMRglu) with significant and most marked increases in the frontomedial and frontolateral cortex (24.3%), anterior cingulate (24.9%), and temporomedial cortex (25.3%). Somewhat smaller increases of CMRglu were found in the basal ganglia (18.5%), and the smallest increases were found in the sensorimotor (14.7%) and occipital cortex (14.4%). The increases of CMRglu in the prefrontal cortex, anterior cingulate, temporomedial cortex, and putamen correlated positively with psychotic symptom formation, in particular with hallucinatory ego disintegration. The present data suggest that excessive 5-HT2 receptor activation results in a hyperfrontal metabolic pattern that parallels comparable metabolic findings associated with acute psychotic episodes in schizophrenics and contrasts with the hypofrontality in chronic schizophrenic patients.

Classification of Schizo-Affective Patients by Multidimensional Scaling and Cluster Analysis

269 patients with schizophrenia, schizo-affective or affective disorders admitted to a hospital in Zürich were examined by the AMP system and the syndrome checklist of Wing and co-workers. The data were analyzed using a special set-theoretical similarity measure for nonlinear graduations, multidimensional scaling to achieve a metric representation of the similarity matrices, and a cluster analysis, originally described by Meisel in 1972.

Stability of psychotic symptomatology (delusions, hallucinations), affective syndromes, and schizophrenic symptoms (thought disorder, incongruent affect) over episodes in remitting psychoses

SummaryA study was made on 140 schizophrenics, 40 schizoaffectives, 59 unipolar depressives, and 30 bipolar affective disorder patients in order to determine the quality of psychopathology over multiple episodes. The schizoaffectives were the most likely to have multiple episodes. Among the schizophrenics, there were few episodes that lacked psychotic symptoms, but almost half of the episodes for the schizoaffectives were asscociated with an absence of psychotic symptoms. Three-quarters of the patients with unipolar depression and bipolar illness showed no psychotic symptoms either congruent or noncongruent. There was a striking finding that all diagnoses were associated with a decrease in psychotic symptoms over time. These psychotic symptoms (delusions and hallucinations) became particularly more scarce among the schizoaffectives, unipolars, and bipolars. There was a 50% to 67% decrease of episodes with psychotic symptoms as more episodes occurred. For schizophrenia and schizoaffective disorder the first ten episodes were very similar to each other for affective syndromes, formal thought disorder and/or incongruent affect, and delusions and hallucinations. It was not until much time had passed that the symptom pictures changed.

A family study of psychotic symptomatology in schizophrenia, schizoaffective disorder, unipolar depression, and bipolar disorder

SummaryAn evaluation was made of schizophrenics (140), schizoaffectives (40), unipolar depressives (59), and bipolars (30), and their relatives who had a chart diagnosis of psychosis or depressive neurosis. The purpose was to determine whether the psychosis (delusions and hallucinations) was transmitted independently of the illness itself. If this were true, there would be an excess of pairs of probands and relatives both positive for psychosis and pairs of relatives and probands both negative for psychosis when compared to relatives and probands who were not concordant for the variable. This was found to be true in schizophrenia and schizoaffective disorder and is probably the result of the simple transmission of an illness which includes the presence of psychotic symptoms in the definition. Thus, this would be a manifestation of the genetic propensity in schizophrenia. For the affective disorders there was no evidence that psychotic probands were more likely than the nonpsychotic to have psychotic relatives. So far the reason why some patients have psychosis and others not in the affective disorders remains unexplained.

Familial syndrome patterns in schizophrenia, schizoaffective disorder, mania, and depression

SummaryA major problem with studies in the field of quantitative genetics is that of phenotypical heterogeneity. In particular, such heterogeneities show up in psychiatric investigations: index cases often tend to display more severe forms of disorders than the respective affected relatives. The principal goal of the present investigation was to test the phenotypical equivalence of the two populations of index cases and their affected relatives. Our analyses were based on 269 hospitalized patients with functional psychoses and 350 affected first degree relatives. As opposed to the majority of earlier investigations in which phenotypes were uniquely defined by diagnoses, phenotypes were represented in this study by a list of 22 psychiatric syndromes. Accordingly, multivariate statistical procedures were applied to analyze the intrinsic properties of the empirical lists. The results showed that typical syndrome patterns clearly appeared in both populations and that the phenotypical equivalence of the corresponding population sample sets lay between satisfactory and good. Furthermore, it was possible to select phenotypically homogeneous and reproducible subsets on the basis of the 22 syndromes. These subgroups can be used as basic material to study the genetic modes via current models from quantitative genetics. Nevertheless, our analyses revealed no clear breeding true of either affective disorders or schizophrenia.

The diagnostic value in assessing mood congruence in delusions and hallucinations and their relationship to the affective state

SummaryAn examination was carried out on 140 schizophrenics, 34 schizoaffective manics, 6 schizoaffective depressives, 59 unipolars, and 30 bipolars to determine the variables of affective states and mood-congruent and mood-incongruent psychotic symptoms. These patients had been admitted to a hospital in Zürich and were systematically diagnosed, using both clinical and computer-derived systems. Forty-eight patients (18%) had both mood-congruent and incongruent psychotic symptoms. However, the affective disorders usually showed mood-congruent symptoms and the schizophrenics the mood-incongruent types. The schizoaffectives were likely to show both types. There was a marked dissociation between affective states and mood congruence in the schizophrenics. Though the majority of these patients showed depressive syndromes, they were quite unlikely to have mood-congruent symptoms. Likewise, 25% of the schizophrenics had manic-like syndromes, which contrasted with the fact that they rarely had mood-congruent psychotic delusions and hallucinations.

Diagnosis of functional psychoses

SummaryThe results of a comparison between the clinical diagnoses of 115 probands with functional psychoses, made on the basis of careful clinical history-taking, interviewing and examinations, and those made by computerized evaluation (CATEGO) on the basis of the present state examination (PSE) were presented. The clinical diagnoses of the project psychiatrist and the provisional classification resulting from the application of the CATEGO program to the PSE symptom profiles were in an overall concordance of 82%. In a second step the 20 cases with differences in diagnoses were reevaluated on the basis of the full history and psychopathology and a syndrome checklist was completed. This reevaluation led to a practically full diagnostic agreement.

Subdividing the functional psychoses: a family hereditary approach

Family genetic data, based on standardized and independent diagnostic procedures of index and secondary cases, confirmed the dichotomy between schizophrenias and affective disorders. The classical schizophrenic subtypes exhibited a significant tendency towards homotypia among their secondary cases. The genetic evidence did not support the monopolar-bipolar subdivision of affective disorder. Schizo-affective disorders impinged on the clear-cut schizophrenic and affective psychotic disorders and there was no homotypical tendency among the relatives of index cases with this diagnosis.

Investigation of gestural and pantomime performance in chronic schizophrenic inpatients.

The present study compared the performance on apraxia tests and additional motor tasks between medicated chronic schizophrenic inpatients (n=21) and healthy subjects (n=21). Praxis testing did not reveal a clear-cut apractic syndrome in the patient group. The most striking difference between patients and healthy controls was the more frequent use of body parts as object (BPO) by schizophrenic patients (P<0.0003). There was no significant difference in psychopathology between subgroups classified according to their BPO performance, although a tendency towards a difference in duration of illness and the actual hospitalization period existed between BPO subgroups. Schizophrenic patients performed more poorly than controls in frontal motor tasks: sequencing, including oral sequential movements, and reciprocal innervation. Frontal motor task performance tended to be related to the negative dimension of schizophrenia in accordance with previous studies. The data do not support the assumption that BPO performance is part of a multidimensional concrete attitude in schizophrenic patients. Nevertheless, this peculiarity in motor behaviour might be a link between neurophysiology and psychopathological phenomenology in schizophrenia. We therefore suggest further investigation focusing the performance of objectrelated pantomime movements in schizophrenic patients.