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The empirical research in premorbid personality of psychiatric patients has markedly advanced in German speaking countries since adequate research methods were introduced in the middle of the sixties. Among the various results are the following: Kretschmer's typological conception of human constitution were largely refuted and replaced by other conceptions on a methodologically more solid ground; Tellenbach's concept of the "melancholic type" as the premorbid structure of the majority of patients suffering from a unipolar affective disorder with melancholic features could be convincingly validated; this concept was supplemented by that of the "manic type" of personality as the premorbid correlate of the amount of a predisposition to manic episodes within the course of an affective disorder; the premorbid deviations of personality in schizophrenics and neurotics were shown to possess little nosological specificity; furthermore, similar deviations could be demonstrated in the personality of (still healthy) relatives of patients with severe mental disorders; the complex relationships of (premorbid) personality, personality disorders and mental disorders were partly clarified.

Personality traits play an increasing role in research on the vulnerability to mental disorders. Problems of their assessment are dealt with here with special reference to work of our own in this area. Personality inventories for self-rating or informants' rating are appropriate instruments for retrospective as well as prospective investigations. They should be short and, at the same time, suites for the assessment of the main dimensions of personality, the "Big Five". The Munich Personality Test (MPT) and the Six Factor Test (SFT) serve as examples in this context. They were already successfully applied in clinical and outpatient settings and in "high-risk" studies. In retrospective investigations, a newly developed method for the operationalized diagnosis of personality types from case history data can be used as well. On the basis of this approach, we have recently developed a Biographical Personality Interview (BPI) which, in combination with personality inventories, can be regarded an optimal device for the assessment of premorbid personality in psychiatric patients.

Only a few studies have investigated the frequency and reasons for depressive states during the clinical treatment of actual schizophrenic psychoses. The constructs used--pharmacogenic depression, postpsychotic depression, akinetic depression etc.--are not well defined and not empirically based. There are contradictory results about the frequency and the course of depressive states during the clinical treatment. We tried to collect informations concerning this problem by analysing the data of 280 acutely schizophrenic inpatients treated with neuroleptics. The data were obtained using standardized rating scales. The ratings were performed by the treating psychiatrists (Inpatient Multidimensional Psychiatric Scale) and by the patients themselves (Clinical Selfrating Scales). The mean scores of depressive syndromes decreased between admission and discharge. On admission 48% of the patients showed a marked depressive apathetic syndrome, only 17% at discharge. Most of the patients, who suffered from a depression at discharge, already had a depressive syndrome of the same or greater intensity on admission. 56% of the 237 patients, who filled out the "acute mood scale", showed a relatively long depression during the clinical stay. These depression were overrepresented in those patients who already suffered from depression on admission. Only 41% of the 237 patients developed a depression without having had depressive mood on admission. The newly developed depressions could possibly be regarded as caused by neuroleptics. However also morbogenic and psychoreactive factors must be taken into consideration to explain these depressions.

There is some evidence that the early response of schizophrenic patients to neuroleptic treatment is of prognostic value for the subsequent course of treatment. This hypothesis was confirmed in a prospective study. It was demonstrated that already the therapeutic effect on the first day of treatment is of prognostic value, especially with a standardized drug regimen.

The antimanic action of high doses of the beta-receptor blocking agent propranolol was investigated by the use of a double-blind placebo controlled ABA design. For comparison, the d-stereoisomer (which is practically devoid of beta-blocking activity) was used. 6 trials were performed with d-propranolol, 6 trials with the racemic mixture. From dose-effect relations one can conclude that the d-stereoisomer is about half as effective against manic syndromes as the racemic mixture. From this finding it can be concluded that the antimanic action of propranolol is at least partially due to a mechanism independent of its beta-blocking action.

Present methodological problems in assessing the clinical efficacy of putative antidepressants require testing of various new strategies. The approach presented by the authors allows "natural" clinical treatments to be evaluated scientifically; double-blind conditions are replaced by other measures of bias control. In this paper, the clinical effectiveness of mianserin in homogenous groups of inpatients with severe endogenous depression is compared with that of maprotiline and amitriptyline. The frequency of change of the respective antidepressant by the physicians in charge as well as patients' self-evaluations based on v. Zerssen's Mood Scale served as outcome criteria. No difference in efficacy was found between maprotiline and amitriptyline, whereas mianserin was significantly less effective. The number of patients complaining of side effects from the two tetracyclic compounds was no less than in the case of amitriptyline. There were, however, qualitative differences; with maprotiline, myoclonic jerks were observed in some cases. The hypothesis that mianserin may possess sedative-anxiolytic rather than antidepressive properties is discussed in conjunction with methodological and theoretical implications.

A double-blind placebo-controlled cross-over investigation of the possible antipsychotic action of [des-Tyr1]-gamma-endorphin (DT gamma E) was undertaken in schizophrenic patients. This non-opiod derivative of gamma-endorphin has recently been shown to exert both neuroleptic-like effects in animals and an antipsychotic action in schizophrenic patients failing to respond to conventional neuroleptic therapy. 13 patients undergoing continuous neuroleptic therapy, and suffering from either chronic or acute, frequently-relapsing schizophrenia and displaying persistent productive symptoms (hallucinations, acute delusions) were selected for the trial. After one day of single-blind injection of placebo, two successive double-blind treatment periods of 4 days each followed, viz 4 days with i.m. injections of 2 mg DT gamma E preceding 4 days of placebo injections or vice versa. Psychopathological evaluation was performed twice daily by use of the IMPS and an eight-point-scale appropriate for the estimation of special target symptoms (VBS). The mean data obtained from the whole sample of 13 patients show that placebo and DT gamma E produce a reduction in symptomatology of an appoximately equal magnitude. The results provide no support for the hypothesis of an antipsychotic efficacy of DT gamma E in the treatment of chronic schizophrenic patients. In the subgroup of acute cases, however, a therapeutic action of DT gamma E appears possible

In a 5-year follow-up study on schizophrenic patients four prognostic scores were developed, based on univariate and multivariate analyses. Three consisted of items on psychopathology and social maladjustment, one only of psychopathological data. In a replication study only the first three could prove their predictive validity.

In 20 psychotic patients with frequent hallucinations and/or actual delusional experience a possible antipsychotic action of the opiate antagonist naloxone (N-allyl-noroxymorphone) was investigated, using a double-blind placebo-controlled cross-over design. 18 of these patients were not treated with neuroleptic drugs; 13 suffered from an acute episode of schizophrenia. Psychopathological changes were assessed by the use of the IMPS-scale and of a symptom-specific rating scale (VBS). Intravenous injection of naloxone (in most cases 4.0 mg) induced a reduction of psychotic symptomatology (especially hallucinations) in the majority of patients. Compared with placebo this effect reached statistical significance within 2-7 hours after injection. From this result a possible involvement of endogenous ligands of opiate receptors in the pathogenesis of schizophrenia may be concluded.

Measurements of beta-endorphin-like immunoreactivity have been performed in CSF and plasma of patients with schizophrenia and other neuropsychiatric disorders. The detection limit of the RIA was between 20--50 pg/ml (6--15 fmole/ml). In CSF the quantity of beta-endorphin-like immunoreactivity ranges up to 65 pg/ml. The data from schizophrenics and other neuropsychiatric patients show no obvious deviation from the results in a control group of medical patients with normal CSF findings. In plasma the immunoreactive beta-endorphin-like material ranges up to 250 pg/ml. There is only a small tendency to higher values in schizophrenic patients, if compared with different types of neuroses and affective and organic psychoses. In a second series of experiments also this tendency could not be reproduced. In 9 electroconvulsive treatments an increase of blood beta-endorphin-like immunoreactivity was observed 7 times. A possible endorphinergic mechanism in the mode of action of electroconvulsion is hypothesized.

A study on 243 schizophrenic inpatients treated with neuroleptics was performed. Using standardized rating instruments a large set of potential prediction variables was tested. Several predictors, known from the literature, could be confirmed, also by cross validation according to the split half technique: among others premorbid disturbances of social adjustment, insidious onset of illness, duration of symptoms before admission, intensity of symptoms at admission, duration of previous hospitalisation. The prognostic scale of Strauss and Carpenter, originally developed for long term prognosis, proved as the most relevant predictor. By stepwise multiple regression analyses an optimal combination of five predictors, explaining 30% to 40% outcome variance was found. The latter result is being tested in a prospective study.