Diagnosing schizophrenia in the initial prodromal phase.

BACKGROUND: In schizophrenia research, early detection in the initial prodrome before first psychotic episodes is a major topic. Therefore, the prognostic accuracy of initial prodromal symptoms was examined prospectively. METHODS: The study sample was composed of patients referred to outpatient departments of German psychiatric university departments, because of diagnostic problems, between 1987 and 1991. They were examined with the Bonn Scale for the Assessment of Basic Symptoms and the Ninth Version of the Present State Examination to detect an incipient schizophrenic disorder. Of 385 patients showing no schizophrenia-characteristic symptoms, between 1995 and 1998, 110 with and 50 without initial prodromal symptoms were followed up and reexamined with the same instruments for a transition to schizophrenia. RESULTS: During a mean follow-up period of 9.6 years, 79 (49.4%) of the 160 patients had transited to schizophrenia. The absence of prodromal symptoms excluded a subsequent schizophrenia with a probability of 96% (sensitivity: 0.98; false-negative predictions: 1.3%), whereas their presence predicted schizophrenia with a probability of 70% (specificity: 0.59; false-positive predictions: 20%). Certain disturbances, such as thought interference, disturbances of receptive language, or visual distortions, predicted schizophrenia, even with a probability up to 91% (specificity: 0.85-0.91; false-positive predictions: 1.9%-7.5%). CONCLUSIONS: The Bonn Scale for the Assessment of Basic Symptoms operationalization of prodromal symptoms performed well in the early detection of schizophrenia. It therefore might be useful for the prediction of the disorder, especially if it is further refined to select those items with particularly high prognostic accuracy.

Effective suppression of luteinizing hormone and testosterone by single doses of the new gonadotropin-releasing hormone antagonist cetrorelix (SB-75) in normal men.

In rats and nonhuman primates the new GnRH antagonist cetrorelix (SB-75; [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,D-Cit6,D-Ala10]GnR H) has been shown to suppress testosterone secretion effectively and persistently. A clinical phase I study was performed to assess the hormonal effects of this highly potent antagonist in normal men. After 2 control examinations 30 young male volunteers were randomly assigned to 6 treatment groups (n = 5/group), and single doses of 0 (placebo), 0.25, 0.5, 1.0, 2.0, and 5.0 mg cetrorelix were administered sc. Blood samples were obtained over the course of 7 days postinjection. After maximal cetrorelix serum levels were achieved 1 h postinjection, the GnRH antagonist serum levels decreased with a terminal t1/2 of 29.8 +/- 4.2 h (mean +/- SE). LH secretion was suppressed dose- and time-dependently; maximal suppression occurred 4-6 h postinjection. Suppression of FSH did not reach statistical significance. Doses of 1.0, 2.0, and 5.0 mg cetrorelix significantly suppressed testosterone secretion compared to that in the placebo group. After the administration of 1.0 mg cetrorelix, maximal suppression was seen 8 h after injection, with testosterone levels of 7.5 +/- 1.1 nmol/L compared to 15.8 +/- 2.2 nmol/L in the placebo group. Maximal testosterone suppression by 2.0 and 5.0 mg cetrorelix occurred 12 h after injection, with testosterone concentrations of 4.9 +/- 0.5 and 2.2 +/- 0.4 nmol/L, respectively, compared to 16.5 +/- 1.7 nmol/L in the placebo group. Twenty-four hours after the injection of 1.0 and 2.0 mg cetrorelix, testosterone values were no longer significantly different from those in the placebo group, whereas in the 5.0-mg dose group testosterone concentrations increased slightly and reached serum concentrations in the lower normal range after 48 h. The only side-effect observed after the administration of cetrorelix was a transient local erythema at the injection site that disappeared within 30 min. No local induration or pruritus, or any adverse systemic side-effect occurred in any volunteer. In conclusion, the new GnRH antagonist cetrorelix effectively decreases serum LH and testosterone concentrations in a dose- and time-dependent manner and, therefore, has potential for treatment of sex hormone-dependent diseases and male contraception.

Regional cerebral blood flow and negative/positive symptoms in 24 drug-naive schizophrenics.

UNLABELLED: SPECT/PET studies in schizophrenia revealed inconsistent changes of regional cerebral blood flow (rCBF). Frontal hyperperfusion as well as hypoperfusion are described. This study was undertaken to investigate the relations between rCBF, psychopathology according to PANSS and effects of neuroleptic therapy. METHODS: Twenty-four drug-naive acute patients with a first manifestation of schizophrenia were examined with 99mTc-HMPAO brain SPECT and assessed according to PANSS. Of these, 22 were controlled again after neuroleptic treatment. Following attenuation correction, region-to-cerebellar count ratios were obtained from 98 irregular regions of interest drawn in all slices (6.25 mm). The ratios were compared to 20 control subjects, and changes lying outside of 2 s.d. were considered abnormal. RESULTS: In different drug-naive patients, hyperperfusion as well as hypoperfused patterns were found. In drug-naive patients, the seven subscores of positive symptoms (pos 1-7) in PANSS showed different correlations to rCBF: Formal thought disorders (pos 2) and grandiosity (pos 5) were positively correlated to bifrontal and bitemporal rCBF (r = +0.59 to +0.70). Delusional ideas (pos 1), hallucinatory behavior (pos 3) and suspiciousness (pos 6) demonstrated a negative correlation to bifrontal, cingulate, left temporal and left thalamic rCBF (r = -0.59 to -0.66). Stereotyped ideas (neg 7) as a negative symptom showed a negative correlation to left frontal, left temporal and left parietal rCBF (r = -0.59 to -0.65). No correlations were found between residual positive symptoms and rCBF after neuroleptic treatment and clinical improvement, but all negative symptoms (neg 1-7) had a negative correlation to bifrontal, bitemporal, cingulate, basal ganglia and thalamic rCBF (r = -0.59 to -0.74). CONCLUSION: Our results illustrate that different positive symptoms are accompanied by different rCBF values: some induce hyperperfusion, others hypoperfusion. After therapy (and reduction of positive symptoms), only negative symptoms correlate exclusively to hypoperfusion. This may be the crucial factor in explaining inconsistencies of past results in perfusion pattern in drug-naive schizophrenic patients.

Are serotonergic reuptake inhibitors more potent in reducing suicidality? An empirical study on paroxetine.

There is some empirical evidence that selective serotonin reuptake inhibitors reduce suicidal ideas faster than other antidepressants. These findings are well in line with the theory of a serotonergic hypofunction in suicidal patients. To test this hypothesis the data of a 6-week double-blind control-group study comparing paroxetine versus amitriptyline were analyzed with respect to suicidality. The global antidepressive efficacy was comparable under dosages of 30 mg paroxetine or 150 mg amitriptyline per day. A differentiated analysis failed to confirm the hypothesis of a faster reduction of suicidal cognitions by paroxetine.

Facet theoretic analysis of the Hamilton-D scale.

The items of the HAM-D(17-item version) were analyzed by a nonmetric (ordinal) multi-dimensional scaling procedure (Smallest Space Analysis, SSA-I) and the structure of the test items characterized within the framework of Guttman's facet theory. Two systematic components (facets) were discerned: 'centrality' and 'aspect'. Properties of the facets as well as their relations were assessed and examined empirically by analyzing the inter-relations among different items. The spatial configurations obtained by the scaling procedure were found only partially to fit the expectations derived from the facet-theory model. The facet 'centrality' was found to have a strong overriding influence over the 'aspect' facet. The results suggest the value of a new combination and selection of items reflecting different facets of depression consistently over time.

Affective instability and impulsivity in personality disorder. Results of an experimental study.

Affective instability in borderline personality disorder is due to a marked reactivity to environmental events. The present study focused on the relationship between affective instability and impulsivity in personality disorder. It used an experimental approach in the form of an affect-stimulation design based on the presentation of a short story which allowed for an analysis of affective responses in regard to quality, intensity, and alterations over time. Impulsive personalities showed a strong intensity of affective responses us well as a tendency towards rapid affect alterations supporting the theory of poor affect regulation in subjects with impulsive self-harming behaviour. Results suggest that affective instability is a crucial part of impulsive personality functioning.

Active and remitted schizophrenia: psychopathological and regional cerebral blood flow findings.

Single photon emission computed tomography with technetium-99m-d,l-hexamethylpropyleneamine oxime (99mTc-HMPAO) was used to assess regional cerebral blood flow (rCBF) during both florid and remitted stages of schizophrenia. Forty schizophrenic patients in an active phase of illness (diagnosis by DSM-III-R) were examined in two clinical states (ill vs. improved). At study entry, 24 patients were drug-naive, five were currently drug-free, and 11 were being treated with antipsychotic medication. Twenty medical patients who suffered from non-specific headaches but were free of neurological and psychiatric symptoms served as control subjects. At initial examination during the active phase of illness, cerebral perfusion patterns in the schizophrenic patients were characterized by both hypofrontality and hypotemporality. After remission, hypofrontality was no longer apparent in two of four frontal regions, and hypotemporality disappeared completely. As assessed with the Positive and Negative Syndrome Scale (PANSS), formal thought disorders, hallucinations, and ideas of grandiosity correlated with rCBF in the active phase of illness, but not after remission. In the remitted but not in the florid state, blunted affect, difficulties in abstract thinking, lack of spontaneity, and stereotyped thoughts correlated with rCBF. Correlations of five symptoms with rCBF changed significantly from first to second examination. The present study suggests that correlations between single psychotic symptoms and rCBF differ significantly in florid vs. remitted phases of schizophrenia.

Factorial structure of the German version of the dimensional assessment of personality pathology-basic questionnaire in clinical and nonclinical samples.

The Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ) assesses 18 traits to provide a systematic representation of the overall domain of personality disorders. We tested the cross-cultural stability of the prediction that four higher-order factors (Emotional Dysregulation, Dissocial Behavior, Inhibitedness, and Compulsivity) underlie the 18 basic traits. A total of 81 patients who were primarily treated for an Axis II personality disorder and N = 166 healthy control patients completed the German version of the DAPP-BQ. Results clearly confirmed cross-cultural stability of the postulated four-factor structure in both samples, accounting for 74.7% (clinical sample), and 65.7% (nonclinical sample) of the total variance. All four higher-order factors showed specific correlational relationships with dimensional assessments of DSM-IV personality disorders.

Special feature: personality and personality disorders. A facet theoretical analysis of the similarity relationships.

Categorical and dimensional models of personality, and personality disorders and their interrelationships, are discussed. A facet theoretical analysis of the structural relationships between personality factors and disorders is described. It is hypothesized that higher-order personality traits organize the personality of both the psychically healthy and the psychically ill, and that personality disorders represent maladaptive variants of traits that are evident in all persons to varying degrees. Data were collected from a clinical (n = 165) and a nonclinical sample (n = 100). Results show that the two classes of variables (personality factors and disorders) have similar relationships to each other, and can be structured in the form of a radex in both samples. Finally, the compatibility of the radex structure with other models is examined, comparing facet theory with factor analytical techniques. The results of the facet theoretical analysis further support the hypothesis of a universal personality model, and a continuous transition from normal personalities to personality disorders.

Phenomenology of simple partial seizures.

Based on a sample of 325 inpatients we present the subjective experiences during simple partial seizures. In a majority of cases, auras comprised composed forms of different symptomatic qualities. We describe rules which seem to govern sequences of aura phenomena. Autonomous and vestibular sensations were shown to have preceding positions related to others, olfactory and gustatory sensations preferred a following position. The tentative explanation of the findings favours the idea of heterogeneity rather than the concept of a focal discharge in a simple partial seizures.

On the conceptualisation of subaffective personality disorders.

The reconceptualisation of German traditional constructs of subaffective personality disorders (PDs) was stimulated by clinical and some empirical evidence of mild and enduring alterations of mood and drive in patients who never developed one of the full-blown mood disorders. The aim of the study was to clarify the status of historical concepts of subaffective PDs (as there are the depressive, hyperthymic, cyclothymic, and asthenic type) in relation to the modern Diagnostic and Statistical Manual (DSM)-III-R conceptions of personality disorders and the five factor theory of personality. A consecutive psychiatric sample and a normal control sample were used to investigate these relationships. By means of a non-metric multi-dimensional scaling procedure, and facet theoretical interpretation, the depressive and asthenic PDs were demonstrated to correspond highly with the global construct of PD as well as with the personality factor neuroticism which proved to be elevated in most types of PDs within the clinical sample. The hyperthymic and cyclothymic categories displayed differences to most DSM-III-R constructs of PD in the clinical but not in the control sample. The findings may explain the chronic course of some depressive or somatization disorders that are difficult to influence by pharmacotherapy and that may require special treatment strategies.

[Acute psychotic productivity in cerebral imaging]. / Akute psychotische Produktivität in der zerebralen Bildgebung1.

Regional cerebral blood flow (rCBF) was analysed in 24 neuroleptically never treated schizophrenics by 99m-Tc-HMPAO-SPECT. Psychopathological symptoms (PANSS) were correlated with rCBF-measures using multidimensional scaling (MDS). Highest degrees of correlation were found for ideas of grandiosity and formal thought disorders compared to different regions of interest (ROIs). An adynamic cluster was defined by basic symptoms which showed signs of deficiency. This cluster was by the highest degree correlated with a cluster defined by rCBF compared to four different clusters of basic symptoms. A fMRI-study was performed in schizophrenic patients with auditive hallucinations in comparison to healthy controls. We offered simple acoustic stimuli perceived as coming from the outside versus inside. For the outside condition, controls activated the medial temporal gyrus on the left side and the rightsided precuneus and postcentral gyrus which represent the auditive source locating and the stimulus processing systems, for inside, they activated the left insula. Hallucinating schizophrenic neither activated the one nor the other system. We discussed the findings as a possible explanation of the schizophrenics' tendency to misinterpret hallucinations as real perceptions.

[Clinical validity of the Beck Depression Inventory. A facet theoretical re-analysis of multicenter clinical observations]. / Zur klinischen Validität des Beck-Depressionsinventars. Eine facettentheoretische Reanalyse multizentrischer klinischer Beobachtungsdaten.

The items of the Beck Depression Inventory are reanalyzed by a non-metric multidimensional scaling procedure (Smallest Space Analysis, SSA-I). The structure of the test items is characterized within the framework of Guttman's facet theory. Two systematic components (facets) are discerned: "centrality" and "aspect". Properties of the facets as well as their relations are assessed and examined empirically by analyzing the interrelations among the items. The spatial configurations obtained by the scaling procedure fit the expectations derived from the facet-theoretic model. The facet "centrality" was found to have a strong overriding influence over the "aspect" facet. The results suggest the introduction of a new combination and selection of items reflecting different facets of depression consistently over time.

[Group experiment to investigate judgement-convergence and the assessment of reality in schizophrenics presented with visual stimuli]. / Gruppenexperiment zur Frage der Urteilskonvergenz und Realitätseinschätzung Schizophrener bei optischem Reizangebot

Eight acute schizophrenics were examined individually and in groups as to their congruence of judgement and as to their accuracy in estimations in response to various visual stimuli; they were compared in these respects with neurotics. The analysis of variance of the power of judgement showed: (a) there was no difference in the two groups of patients beyond what could be expected by chance alone, and (b) the congruence of judgement was the same in both groups. The analysis of variance of the accuracy in estimations showed that with increasing numbers of stimuli in the visual field the schizophrenics became less and less precise in their estimates. It was demonstrated under what conditions social-psychological findings can be applied to schizophrenic psychoses.

[Dysfunctions of space perception and spatial ability in schizophrenia (author's transl)]. / Uber Störungen des räumlichen Wahrnehmungs- und Vorstellungsvermögens bei Schizophrenen

Thirty-seven acute schizophrenics and 25 normal subjects were investigated with regard to their spatial perception, representation, and their spatial ability, Schizophrenics showed significantly poorer performances (in terms of quantity) in those variables, which characterized the ocular apprehension of structures and wholes, the relation of parts to a whole, or the analysis of a whole in its various components as well as the availability of visual engrams, partly in the sense of spatial representation, and the practical realization of imagined spatial configurations. On the other hand, in ocular apprehension, interpretation, and when necessary the practical realization of two-dimensional represented spatial symbols and configurations and perspective abilities there was only statistical trend for quantitatively poorer performances in schizophrenics compared with healthy persons. Factor analysis of the intercorrelation matrices for 14 variables separated out the same 4 factors in each group for space perception and spatial ability. In spite of the demonstrated "quantitative" differences for the single variables between the two groups a marked similarity in a "qualitative" sense was found, when the two-factor structures were compared mathematically (similarity coefficient: 0.664). In order to specify these differences, 56 schizophrenics were classified as paranoid or nonparanoid and investigated in the above-mentioned manner. While these groups did not show any significant quantitative difference concerning their performances at variable level, they showed entirely different structures using factor analysis. Spatial perception of the paranoid schizophrenics seemed less structured and their perceptual conception less systematical. On the other hand, when factor structures from nonparanoids and healthy controls were compared mathematically, both groups showed a marked similarity (0.783). An attempt was made to relate these results to other findings of literature and to theories of cognitive and perceptual dysfunctions of schizophrenics.

Psychotherapeutic effects by audiovisual heteroconfrontation in a case of anorexia nervosa.

After a short overview about the use of audiovisual methods in psychiatry and psychotherapy we present a single case study of a young woman suffering from anorexia nervosa. In a typical way the patient could not accept the idea that she had an emotional disorder and did not accept being admitted to hospital or to come as an outpatient to psychotherapeutic treatment. We used the method of audiovisual heteroconfrontation, i.e., she was confronted with the videotape of another patient suffering from the same disorder. After four sessions of confrontation she was extremely occupied with herself, she suffered more from her condition and was motivated to undergo psychotherapy. Finally, the process of heteroconfrontation is discussed.

[Causal analytic studies on demonstration of neuroendocrine parameters in combined hypoglycemia test in depressive subgroups]. / Kausalanalytische Untersuchungen zur Darstellung neuroendokriner Parameter im kombinierten Hypoglykämietest bei depressiven Subgruppen.

With the help of an analytical path structure model (causal analysis) the aim of the study was to elucidate further, in female patients with various depressive disorders, some correlations of causal interdependencies between changes both in basal secretion of anterior pituitary hormones and in their responses to the (combined) insulin tolerance test (ITT) with extraneous factors--such as age, deviation from ideal body weight (in percentage), severity of depression and score in the Newcastle Scale (NCS)--that may influence these abnormalities. In various depressive subgroups the strength of influence and the different importance of deviation from ideal body weight and basal growth hormone (GH) concentration (as exclusion criteria) for their neuroendocrine reactivity in the combined ITT was shown. The hypothesis that cortisol hypersecretion may be the primary disturbance and the other possible neuroendocrine changes such as blunted GH, cortisol and TSH responses to stimuli in some depressive patients all may be secondary to the (elevated) cortisol level could not be corroborated. The endogenous mono- and bipolar subtypes of major depressive disorders showed intimate connections between the various neuroendocrine functional systems and the above mentioned extraneous factors resulting in a narrowed variability and a stronger coupling in the reactivity of these hormonal functional systems, a condition which can be seen as analogous to experimental results at the psychophysiological level in these nuclear groups of depressed patients, whose psychopathological state is also characterized by similar limitations in their "degree of freedom" (Heimann).

[Presentation of information for the diagnostic-therapeutic decision of the psychiatrist]. / Zur Informationsmenge bei der diagnostisch-therapeutischen Entscheidung des Psychiaters

So far, little systematic work had been done to investigate how information regarding psychiatric cases should best be presented in order to facilitate important medical decisions. For each of three groups of diseases: (a) schizophrenic reaction, paranoid, (b) manic-depressive, depressed, and (c) anxiety neurosis, we have described four different cases, systematically varying both quantitatively and qualitatively the information in each description. Categorical judgement was given by 15 psychiatrists on a nine-step rating scale with regard to three dimensions. In order to investigate the constancy of the judgements, the method of scaled pair comparisons was used according to the law of comparative judgement. After examination of the adequacy of the scaling models, the following results, among others, were obtained from the scale scores: the discrimination of the two cases of psychoses was highly significant, that of the anxiety neurosis was not significant.

Mood curves of neurotic-depressive patients undergoing treatment with antidepressants: time-series analyses of experience with HTAKA model.

Statistical time-series analyses of single case data allow a sophisticated person-centered evaluation of therapeutic effects. The possibilities and limitations of a new method of time series analysis are shown by the example of mood curves of neurotic depressive patients. The HTAKA model seems advantageous, because this procedure is less restrictive than other methods as regards the data basis. The cluster-analytical agglomeration of the single-case results indicates a sufficient response to antidepressants in about 40% of the patients who were treated with antidepressants in addition to psychotherapy.