The hypothalamic-pituitary-thyroid axis in patients with schizophrenia.

Serum concentrations of thyroxine (T(4)), triiodothyronine (T(3)), reverse triiodothyronine (rT(3)) and thyrotropine (TSH) were measured in 31 acutely ill in-patients with schizophrenia before and after four weeks of treatment with the phenothiazine derivative perazine. The serum levels of all the above hormones were also determined in 19 schizophrenic patients in remission who were receiving no medication, 20 schizophrenic patients in remission taking neuroleptic drugs, and 24 patients with residual-type schizophrenia. The serum levels of T(4) of acutely ill schizophrenic patients were elevated, while those of T(3), rT(3) and TSH were normal. Their T(4) levels showed a positive correlation with the severity of illness and the degree of clinical response to neuroleptic treatment. There was a significant fall in serum concentrations of T(4) and rT(3) during four weeks of drug treatment and the decrease was significantly correlated to clinical response. No abnormalities in the serum concentrations of any of the hormones measured were found in schizophrenic patients in remission or in residual-type schizophrenia. In conclusion, our results indicate that the elevated serum levels of T(4) may be specific for acutely ill schizophrenic patients and that neuroleptic medication may affect thyroid hormone metabolism, this interaction being involved in the mechanism of action of these drugs.

Prospective study of course of illness in schizophrenia: Part I. Outcome at 1 year.

In a prospective study involving 161 patients discharged from inpatient psychiatric treatment, outcome data were obtained for 93 percent of the patients 1 year after clinic discharge. Sixty-seven percent of the patients were directly interviewed for the followup examination. Outcome data for symptomatology, relapses, employment, and social contacts did not differ significantly for patients with schizophrenic psychoses as compared to those with affective psychoses, neuroses, and other psychiatric diagnoses (predominantly alcohol dependency). A discrepancy between self-ratings and observer-ratings was particularly striking in the group of neuroses at discharge from inpatient treatment. These patients also had comparatively more prominent depressive symptomatology at followup. These findings raise questions about the influence of possibly different levels of intensity in outpatient followup treatment, and about outcome predictors independent of diagnosis. These questions are pursued in Parts II and III.

Prospective study of course of illness in schizophrenia: Part II. Prediction of outcome.

In a prospective study of the course of illness of 86 schizophrenic patients (ICD 9), outcome data were obtained for 86 percent 1 year after clinic discharge. The Strauss-Carpenter Outcome Scale (frequency of social contacts, employment duration, symptomatology, and duration of rehospitalization) and the Clinical Global Impressions were used to assess outcome. The prognostic scales developed by Vaillant, Stephens, Phillips (in the abbreviated version by Harris), and Strauss-Carpenter were used as potential outcome predictors at the time of index admission. The findings were as follows: The outcome criteria used correlated at best moderately with one another. Between 60 and 90 percent of the sample were judged to have an unfavorable prognosis on the Vaillant and Stephens scales. In contrast, the outcome was relatively favorable for 50 to 60 percent of the patients. In prognostic validity, the Strauss-Carpenter scale was superior to all of the other scales investigated. However, a prognostic relationship was only established for social outcome. Social outcome dimensions showed the highest prognostic validity (e.g., employment and social contacts). The amount of variance explained by the best predictors was between 12 percent (symptomatology) and 55 percent (employment duration).

Prospective study of course of illness in schizophrenia: Part III. Treatment and outcome.

In a prospective study of 86 schizophrenic patients (ICD 9), outcome data were obtained for 86 percent 1 year after clinic discharge. The Strauss-Carpenter outcome scale (frequency of social contacts, employment duration, symptomatology, and duration of rehospitalization) served as the outcome criterion. The Strauss-Carpenter prognostic scale items served as the potential predictors of the course. The followup treatment, which took place during the catamnestic period, was compared with that of other psychiatric diagnostic groups with respect to its continuity and efficiency. The following findings emerged: When compared to patients with neuroses and alcohol dependency, the followup treatment of schizophrenic patients in a large city seems to be better ensured. This is attributed to a clearer concept of treatment for schizophrenic patients. The comparatively favorable outcome of this group of patients seems to be related to this. For the other groups, especially for neurotic disorders, effective treatment concepts have still to be developed and evaluated. Schizophrenic patients receiving continuous neuroleptic medication are rehospitalized significantly less often (28 percent) than those not in continuous treatment (55 percent). This treatment difference is most obvious for patients with multiple admissions. Differences dependent on treatment are not found in other outcome dimensions. However, patients with good heterosexual adjustment profit the most from continuous treatment with neuroleptics in reference to freedom from symptoms. For a more chronic subgroup with a poorer initial level of work adjustment, the functional level deteriorates over the course of illness. Relapse and inpatient readmission are related to retarded recompensation, particularly for chronic patients. This underlines the need for consistent neuroleptic treatment.

A prospective study of factors influencing adherence to a continuous neuroleptic treatment program in schizophrenia patients during 2 years.

Dropout from prophylactic neuroleptic treatment is one major reason for relapse in schizophrenia patients. There is a lack of prospective studies on factors that predict medication adherence. We investigated factors suspected to predict dropout from continuous neuroleptic treatment in a 2-year prospective study involving 122 outpatients with a DSM-III-R diagnosis of schizophrenia. Forty-two (34.4%) were classified as patient-related dropouts. No significant difference between compliant patients and dropouts was found with regard to sociodemographic variables, except that compliant patients were significantly older. Also, no differences in psychopathology were seen at the beginning of treatment, but compliant patients had a longer duration of illness. Compliant patients had higher doses of neuroleptics in the initial stabilization phase and correspondingly showed more extrapyramidal signs. Physicians rated compliant patients from the beginning as more cooperative. These patients also showed significantly higher scores in positive treatment expectations. In a stepwise regression analysis, positive illness concepts, the global assessment of functioning (GAF), and the physicians' view of patients' cooperation predicted 19 percent of the variance. We concluded that the prediction of dropouts is insufficient and remains largely an unsolved problem. Future research should focus more on context factors in the search for clinically meaningful explanations of patient dropout from treatment.

Predictors of relapse and rehospitalization in schizophrenia and schizoaffective disorder.

In a German multicenter treatment study, 354 patients with schizophrenia and schizoaffective disorder were followed for 2 years. The data collected were taken as a basis for the present predictor study. For the first time, the technique of classification and regression tree (CART) analysis has been employed for this purpose. CART yielded informative data and appeared to be a useful instrument in predictor research. On the outcome variables "relapse" and "rehospitalization," significant predictor variables were found in several areas: neuroleptic treatment, onset and previous course (precipitating factors, first manifestation, hospitalization in the preceding year, suicide attempts), psychopathology (residual type, schizoaffective disorder), social adjustment (marital status, employment, intensity of life, Phillips score), previous life experiences (traumatic experiences and psychiatric or developmental disturbances in childhood), and biology (gender, age). Our investigation confirmed the generally prevalent views regarding the value of neuroleptic treatment, the multifactorial etiology, and the vulnerability stress model of schizophrenia.

Depressive Syndromes and Scales in the AMDP-system.

The Association for Methodology and Documentation in Psychiatry was founded in 1965 by a group of psychiatrists from Germany, Switzerland and Austria. It developed a uniform and comprehensive system for the documentation of psychopathological, somatic, and anamnestic findings, the AMP-System. In 1979 a revised system was introduced, the AMDP-System. In the AMP-System there are 5 suggestions as to syndrome scale construction based on analyses of data of psychiatric clinics in Munich (2 samples), in Zurich (1 sample), and in Berlin (2 samples). The corresponding syndromes of the different solutions are highly intercorrelated. In the AMDP-System final syndrome scales were constructed on the basis of combined samples of the psychiatric clinics of the universities in Munich and in Berlin. The AMDP syndrome scales show a high similarity with the AMP syndrome scales, whereby a good comparability is ensured between older studies using the AMP- and present studies using the AMDP-System. All syndrome scale solutions include, besides 6 or 7 other syndromes, like a paranoid-hallucinatory and a manic syndrome, two syndromes especially pertinent to the assessment of depressive states: the depressive and the apathy syndromes. The syndromes are described and it is shown how they and other syndromes discriminate different depressive diseases (defined by ICD-diagnoses). There is a considerable overlap in psychology between the diagnostic groups - in spite of a remarkable good discrimination of these groups by psychopathological syndromes - therefore the patients were classified de novo by cluster analysis in more homogenous groups regarding psychopathology. The results are illustrated by some "depressive" clusters in comparison to depressive diagnostic groups.

Is interval medication a successful treatment regimen for schizophrenic patients with critical attitudes towards treatment?

In neuroleptic long-term medication, only part of the patients accept regular intake of neuroleptic drugs. The question is whether an interval medication regimen as opposed to continuous medication can help to reduce drop outs in patients with critical attitudes towards long-term medication. In a 2-year prospective study, 122 patients were randomised to an interval and 164 to a continuous neuroleptic medication regimen. The drop out rates were 62.5% in the interval and 53.7% in the continuous medication group. Drop outs generally show more negative attitudes towards treatment. Patients with negative attitudes do not do better under interval medication. Moreover, this regimen even requires more cooperation and trust in terms of the necessity of medication on the part of the patient compared to the continuous medication regimen. Interval medication therefore is a strategy which can only be successful in highly cooperative, but not in treatment-reluctant patients.

Early neuroleptic intervention in schizophrenia: are prodromal symptoms valid predictors of relapse?

All recently completed controlled two-year studies on intermittent, early neuroleptic intervention treatment have failed to compare favourably with studies on maintenance treatment concerning relapse prevention. The reason for this failure is still unclear. Therefore the implicit, but as yet unproven, hypothesis that a relapse can be predicted from prodromal symptoms was tested from the perspective of our German multicentre study. Results demonstrate that this is not the case. Possible reasons for and clinical implications of this negative finding are discussed.

A German multicentre study on the long-term treatment of schizophrenic outpatients.

Planning a major, multicentre study on effects of neuroleptic treatment in schizophrenic outpatients requires attention to many methodological, ethical and administrative matters. This report describes the study planned by the German neuroleptic therapy study group. Three types of treatment have been chosen: prophylactic maintenance medication, neuroleptic crisis intervention and prophylactic early intervention. Patients who meet the criteria for inclusion in the study are assigned to each treatment on a random basis, provided their informed consent has been obtained. Their psychopathological symptoms, social status and physical condition are measured by means of standardised examinations and rating scales. The study is expected to continue during five years, after which computerised data analysis will be carried out to test the central hypotheses for the study.

[Influence of social factors on the success of psychopharmacotherapy]. / Der Einfluss sozialer Faktoren auf den Erfolg einer Psychopharmakotherapie.

The course of a mental disease is influenced by a multitude of social factors modifying the necessity and efficiency of treatment via drugs, e.g. neuroleptics. The influence of overriding social factors on the course of a disease is demonstrated, employing schizophrenic diseases as an example: Unemployment increases the admission rate of schizophrenics; schizophrenias take a more favourable course in developing countries than in industrialised countries; in the latter category, rural districts are more favourable than the urban regions with major cities. In acute schizophrenia, the healing process is promoted by a clear-cut and well structurised therapeutic environment in the hospital, whereas a loosely knit and permissive environment delays the curative process. Social factors are particularly important in prophylactic neuroleptic long-term treatment designed to prevent relapses; in this connection, special attention is drawn to the importance of emotionalism governing the attitude and behaviour of family members. These social factors influencing the course of the disease make it necessary to supplement drug treatment by suitable measures in the fields of psychotherapy and sociotherapy.

[Medical expert assessment in psychiatry]. / Arztliche Begutachtung in der Psychiatrie.

Especially regarding two respects, the psychiatric expert assessment differs from the expert assessment of other medical specialties: (1) No laboratory tests or technical equipment are available for the psychiatrist except for mental disturbances due to physical impacts such as brain injuries or intoxications. The psychiatrist depends on a carefully compiled case history and a differentiated psychodiagnostic. This may lead to a wrong assessment due to a lack of objectiveness. (2) There are a lot of legal areas where only the psychiatric or psychological expert opinion is required: i.e., the question of criminal responsibility during a trial, the assessment of legal capacity and the capability to will, for decisions about the custody of children etc. This is demonstrated with some cases as an example.

One-year outcome of schizophrenic patients--the interaction of chronicity and neuroleptic treatment.

In an ongoing prospective investigation of the course and outcome of schizophrenia, the global functioning (employment, social contacts, symptoms) and rehospitalization rate of 72 patients were assessed one year after clinical discharge. With regard to chronicity of illness, the global outcome was better for first admissions than for multiple admissions. On controlling the patients' functioning one year before index admission, this difference did not hold true. Hence, there must be difference in the functioning of the two groups which dates back a rather long time. However, multiple admissions showed an actual downward trend in their work functioning (p less than 0.05). Rehospitalization rates of the two groups did not differ significantly (33% for first admissions versus 40% for multiple admissions). Evaluation of differences in drug-taking behavior revealed that patients with better global functioning tended to take their neuroleptics not as regularly as prescribed. Whereas for good functioning first admissions, taking into account, their better spontaneous course (rehospitalization rate 27%), an intermittent neuroleptic strategy may be in order, for multiple admissions the reversal seems to be true (rehospitalization rate for compliant patients 27%, for non-compliant patients 73%, p less than 0.01). However, a small group of good functioning multiple admissions did not have to be rehospitalized in spite of non-compliance, whereas the patients with the poorest function relapsed despite their compliance. We conclude that, whereas for first admissions long-term neuroleptic medication may not be generally indicated on account of their prognostic heterogeneity most of the multiple admissions will profit by this therapeutic strategy in respect of rehospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Multidimensional study of the outcome of schizophrenic patients 1 year after clinic discharge. Predictors and influence of neuroleptic treatment.

Several dimensions of the outcome of 86 schizophrenic patients were recorded 1 year after discharge from inpatient index-treatment to complete a prospective study concerning the course of illness (rehospitalization, symptoms, employment and social contacts). When compared with 75 psychiatric patients of other diagnostic groups, no differences were found other than a significantly longer average rehospitalization stay for the schizophrenic patients. Taking prognostic categories and the regularity of neuroleptic therapy conducted during follow-up into account, it was established that the social outcome status of schizophrenic patients is substantially determined by the original level at the time of index-treatment. In contrast, the rate of relapse and readmission depend significantly upon the continuity of neuroleptic treatment. More complex analyses show that particularly for patients already hospitalized several times, successful relapse prophylactic treatment also has a favorable influence upon the patients' symptoms in the sense of a more stable remission. This could be related to the finding that the more chronic patients apparently exhibit a delayed remission when they undergo a relapse. The findings are interpreted to the effect that continuous neuroleptic maintenance therapy is advantageous to the majority of the patients, and should be applied, in view of the fact that alternative therapy procedures such as neuroleptic interval strategies have not yet been sufficiently evaluated.

[Validity of the syndrome scales in the AMDP-system]. / Zur Validierung der AMDP-Syndromskalen.

To examine the validity of the syndrome scales of the AMDP system, various diagnostic groups as defined by the ICD were described by these scales and distinguished from each other by discriminant analyses. As a comparison the same diagnostic groups were distinguished using the syndrome scales of the AMP system. The analyses using the AMDP system were performed in a sample of 659 patients of the Psychiatric Clinic of the Free University of Berlin during 1979-1980, the analyses with the AMP system in a sample of 2269 patients of the same clinic during the period 1971-1976. It could be shown that different endogenous and organic psychoses as well as neuroses can be described in their psychopathology and discriminated from each other by means of the syndrome scales of the AMDP system. The validity of the syndrome scales in relation to this criterion could be proved. Moreover, we found a high similarity between the results with the AMDP system and the results with the AMP system, which demonstrates that the two systems compare well.

Prognosis of the course of schizophrenic psychoses compared to other psychiatric illnesses. Catamnestic treatment and outcome 1 year after discharge.

In a prospectively designed study of the course of illness of 161 hospitalized psychiatric patients, data regarding outcome could be obtained for 93% 1 year after clinic discharge. It was possible to reexamine 67% of the patients by means of direct interviews. No significant differences appeared in the comparison of the course of illness outcomes (symptoms, rehospitalization, occupation and social contacts) of patients with schizophrenic psychoses, affective psychoses, neuroses or a group of mixed other diagnoses (predominantly alcohol dependency). For the group of neuroses there was a particularly striking discrepancy between the self- and the observer-ratings at the time of discharge from inpatient index-treatment. From this finding and from the comparatively more intense prominence of depressive symptoms at the time of follow-up, one can presume that there has been insufficient after-care treatment of this patient group considering the recorded treatment data. This seems to hold true for the group of alcohol dependents as well. In contrast, the after-care treatment of patients with affective and schizophrenic psychoses seems more likely to be ensured today. Despite this, however, for the latter the close link between the rate of relapse and the rate of rehospitalization can apparently scarcely be influenced.

Sex differences in the psychopathology of inpatients.

In a sample of more than 2000 patients from the Department of Psychiatry of the Free University of Berlin (58.8% men, and 41.2% women), the sex differences in the diagnostic distribution and in the severity of the depressive symptomatology were investigated on the basis of data documented by the AMP system. Due to patient selection by the hospital, men with depressive neuroses were found to be over-represented contrary to expectation; depressive psychoses, however, were prevalent in women as expected. In the total group of patients, depressive symptomatology at the symptom and syndrome levels prevailed in women. Within homogeneous diagnostic groups, depressiveness in minor depressive disorders like depressive neuroses was more severe in women, but in psychotic depression men were more seriously depressed than women. Attempts are made to interpret these findings on the basis of constitution-biological and role-theoretical concepts, but especially on the basis of sex-specific help-seeking behaviour.

Prediction of "natural" course, relapse and prophylactic response in schizophrenic patients.

Three problems in the prediction of the long-term outcome of schizophrenia are illustrated by the results of three separate studies: The limitations of the possibility of generalizing results, the limits being due to the given historical and sociocultural settings. This determines the results of research. The relationships between different types of predictors and targets. The disease-related specificity of predictors. A prospective 1-year follow-up study comparing 100 schizophrenic patients in a rural region with 200 schizophrenic patients in an urban region shows regional differences in outcome criteria, such as rate of hospitalization. The prognostic significance of the various predictors is also different in the two regions. A follow-up study of 70 schizophrenic patients, who were continuously treated with neuroleptic drugs in our outpatient clinic after hospital discharge for an average of 14 years, shows a relatively good outcome. Several outcome dimensions (rehospitalization rate, symptoms, social and work adjustment, self-ratings) are partly mutually independent. The various outcome dimensions are predicted by different predictor patterns. A prospective follow-up study of 86 schizophrenic patients compared with 75 patients with other psychiatric diagnoses confirms the finding of the partly low intercorrelations of the different outcome criteria. The study additionally shows that the predictors of some outcome dimensions, such as work adjustment, are non-specific in respect of diagnosis.