Biomedical subjects

W an der Heiden

Publications and source records attributed to W an der Heiden.

At least 19 recordsLinked to original sources

PubMed2001

Recovery from psychotic illness: a 15- and 25-year international follow-up study.

BACKGROUND: Poorly defined cohorts and weak study designs have hampered cross-cultural comparisons of course and outcome in schizophrenia. AIMS: To describe long-term outcome in 18 diverse treated incidence and prevalence cohorts. To compare mortality, 15- and 25-year illness trajectory and the predictive strength of selected baseline and short-term course variables. METHODS: Historic prospective study. Standardised assessments of course and outcome. RESULTS: About 75% traced. About 50% of surviving cases had favourable outcomes, but there was marked heterogeneity across geographic centres. In regression models, early (2-year) course patterns were the strongest predictor of 15-year outcome, but recovery varied by location; 16% of early unremitting cases achieved late-phase recovery. CONCLUSIONS: A significant proportion of treated incident cases of schizophrenia achieve favourable long-term outcome. Sociocultural conditions appear to modify long-term course. Early intervention programmes focused on social as well as pharmacological treatments may realise longer-term gains.

Adult↗

PubMed2000

Main risk factors for schizophrenia: increased familial loading and pre- and peri-natal complications antagonize the protective effect of oestrogen in women.

Women fall ill with schizophrenia 3 to 4 years later than men. The neurobiological mechanism, explaining the delay of onset in women until menopause, is presumably due to a sensitivity reducing effect of oestrogen on central d(2) receptors, as we have previously shown in animal experiments and in a controlled clinical study. The gender difference in age at onset seems to disappear in familial cases with schizophrenia, but it increases to highly significant values of 5 years or more in isolated cases according to a recent study by Albus and Maier (Schizophrenia Research 18:51-57, 1995). We tried to replicate these findings and to test the hypothesis of a functional antagonism between genetic predisposition to illness and the protective effect of oestrogen in a population-based sample of 232 first illness episodes of schizophrenia. In women with at least one first-degree relative suffering from schizophrenia, age at onset defined by first psychotic symptom was significantly reduced by several years and the difference with men disappeared. In sporadic female cases (no mental disorder in first-degree relatives) the age at onset was slightly increased compared with the total sample, which was in accordance with our hypothesis. In men with familial schizophrenia, but without a protective agent like oestrogen, the age at onset was only slightly and non-significantly reduced compared with the total group and with sporadic cases. This was in line with Albus and Maier and with our hypothesis that only the protective effect of oestrogen could be antagonized by a strong genetic disposition. The second main risk factor for schizophrenia is pre- and peri-natal complications. We compared men and women from our sample of first illness episodes with a history of pre- and peri-natal complications with those without a history of obstetric complications. In women the age at first psychotic symptom was markedly reduced, but due to small case numbers not significantly, compared with women without the risk factor and with the total group. Again, schizophrenic men with a history of pre- and peri-natal complications showed only a small, non-significant reduction of age at onset compared with the total and the group without the risk factor. Therefore, we concluded that the degree of genetically determined vulnerability and, presumably to a slightly lesser extent, the degree of pre- and peri-natal brain injury antagonizes the onset delaying effect of oestrogen in schizophrenia.

Adolescent↗

PubMed2000

The epidemiology of onset and course of schizophrenia.

Traditionally the heterogeneity of schizophrenia was dealt with by subdividing the syndrome into different subtypes. However, due to lacking standards, the result was an immense variety of subtypes partly based on cross-sectional assessments, partly taken the whole course between onset, resp. first admission and outcome after many years into account. Some solutions were based on symptomatology only, others also relied on social characteristics as the ability to fulfil different roles in family and the world of employment. So it is not surprising that the number of subtypes ranges from two up to more than 70. As one possible solution Carpenter and Kirkpatrick (1988) suggest that attempts to subdivide the schizophrenic syndrome should concentrate on few significant parts of the course thought of to represent specific disease processes. Based on two epidemiological studies finding about the onset, middle course and late course of schizophrenia are presented. In three quarter of the cases the onset of the first psychotic episode in schizophrenia is preceded by a prodromal phase with a mean length of about five years. The earliest signs of the disorder are depressive and negative symptoms. Early depressive symptoms predict higher overall symptom scores in the first illness episode and lower scores for affective flattening in the medium-term course. There is no decrease in the number of patients with acute symptomatology over fifteen years after first hospital admission, rather there is a tendency of an increase. With respect to social abilities we found a significant increase of disability over time. But the change already takes place during the first five years. Approx. 60% of those falling ill with schizophrenia become chronic and approx. 25% will recover during the first five to six years.

Adolescent↗

PubMed2000

[Methodological problems of longitudinal studies on schizophrenia].

Longitudinal studies are a key to understanding schizophrenia. They are the more informative, the longer the periods covered. Hence, good studies into the course of schizophrenia almost exclusively involve a lot of effort and cost. In practice, however, time-consuming methods and design variables must be avoided. The pitfalls this constraint produces are instructive of the difficulties longitudinal studies are faced with in striving for valid results. For reasons of research economy, requirements must be adjusted to study objectives. Studies into the short term course are less time-consuming, but because of the rapid changes in the illness course study intervals should be defined clearly and observed strictly. In long-term studies, too, one source of error lies in the highly varying lengths of illness of the patients studied. Even some of the classic long-term studies are marred by this error. The beginning of the follow-up period should be comparable across the study cohort and as close to illness onset as possible. To obtain generally valid results the probands must be representative of all the illness cases in the general population not only at the outset, but also all the later stages of the study. Besides the efforts to avoid attrition in the study cohort, ways must be found for correcting and estimating data for an acceptable proportion of drop-outs. In the analysis of course and outcome the indicators chosen must be apt to the traditional subtypes as well as to a theoretical symptom patterns and empirical symptom structures. In the context of typical design variables of longitudinal studies the assets and weaknesses of two retrospective and one prospective design will be discussed. Concerning the social course, importance of disease-independent factors, such as age, sex and level of social development at illness onset, as well as of control groups will be demonstrated. Predictor models will be discussed with reference to the direct and indirect influences involved. Examples of such analyses will be given.

Humans↗

PubMed1999

The course of schizophrenia in the light of modern follow-up studies: the ABC and WHO studies.

In schizophrenia most of the social consequences emerge in the prodromal phase of the illness and before treatment is initiated. Further course is determined by the level of social development at illness onset and by age- and sex-related illness behavior. Despite the sex difference in age at onset the disease process seems to be the same in both sexes, since social course in men and women converges in the long run. Although great variation in outcome between the patients is to be observed at each cross-section, the medium and long-term symptom-related course of schizophrenia shows a high degree of stability at the individual level.

Adult↗

PubMed1999

Depression, negative symptoms, social stagnation and social decline in the early course of schizophrenia.

OBJECTIVE: The aim of this study was to investigate when social consequences in schizophrenia emerge, and what conditions give rise to the social disadvantage evident in people suffering from schizophrenia. METHOD: Early course in schizophrenia was studied in a population-based sample of 232 first illness-episode cases retrospectively from onset to first admission, and in a representative subsample of 115 patients prospectively at six cross-sections over a period of 5 years. Data on non-specific and negative symptomatology and social development was compared with data from an age- and sex-matched control group drawn from the normal population. RESULTS: In total, 73% of the patients showed a prodromal phase of several years. First signs were depressive and negative symptoms. In 57% of cases social disability emerged 2 to 4 years before first admission. Social consequences depended on the level of social development at onset. An early onset involved social stagnation, and a late onset was associated with social decline. Men's poorer social outcome was determined by their lower level of social development at onset and socially adverse illness behaviour. The 5-year symptom-related course showed no gender difference. At 81% the lifetime prevalence of depressive mood until first admission was several times higher in schizophrenics than in healthy controls. Early depression predicted a lower subsequent score for affective flattening. Suicide indicators were predicted by lack of self-confidence and feelings of guilt early in the illness. CONCLUSION: Taking into account a prodromal phase of several years on average before first hospital admission, early detection, case identification and intervention are urgently needed. The intervention must be targeted at syndromes such as early depression, negative symptoms and certain forms of cognitive and social impairment.

Adult↗

PubMed1998

The ABC Schizophrenia Study: a preliminary overview of the results.

The ABC Schizophrenia Study, a large-scale epidemiological and neurobiological research project commenced in 1987, initially pursued two aims: (1) to elucidate the possible causes of the sex difference in age at first admission for schizophrenia and (2) to analyse the early course of the disorder from onset until first contact and its implications for further course and outcome. First, transnational case-register data (for Denmark and Germany) were compared, second, a population-based sample of first-episode cases of schizophrenia (n = 232) were selected and third, the results obtained were compared with data from the WHO Determinants of Outcome Study by using a systematic methodology. A consistent result was a 3-4 years higher age of onset for women by any definition of onset, which was not explainable by social variables, such as differences in the male-female societal roles. A sensitivity-reducing effect of oestrogen on central D2 receptors was identified as the underlying neurobiological mechanism in animal experiments. Applicability to humans with schizophrenia was established in a controlled clinical study. A comparison of familial and sporadic cases showed that in cases with a high genetic load, the sex difference in age of onset disappeared due to a clearly reduced age of onset in women, whereas in sporadic cases it increased. To analyse early course retrospectively, a semistructured interview, IRAOS, was developed. The early stages of the disorder were reconstructed in comparison with age- and sex-matched controls from the same population of origin. The initial signs consisted mainly of negative and affective symptoms, which accumulated exponentially until the first episode, as did the later emerging positive symptoms. Social disability appeared 2-4 years before first admission on average. In early-onset cases, social course and outcome, studied prospectively over 5 years, was determined by the level of social development at onset through social stagnation. In late-onset cases, decline from initially high social statuses occurred. Socially negative illness behaviour contributed to the poor social outcome of young men. Symptomatology and other proxy variables of the disorder showed stable courses and no sex differences. Further aspects tested were the sequence of onset and the influence of substance abuse on the course of schizophrenia, primary and secondary negative symptoms, structural models and symptom clusters from onset until 5 years after first admission.

Adolescent↗

PubMed1998

Causes and consequences of the gender difference in age at onset of schizophrenia.

The ABC (age, beginning, course) schizophrenia study was commenced in 1987 to generate and test hypotheses about pathogenic aspects of schizophrenia. One of the main branches of the study focused on how gender influences the age distribution of onset, symptomatology, illness behavior, and early course in schizophrenia. Proceeding from one of the rare, strikingly deviating, consistent findings--the gender difference in age at first admission--we launched a systematic search for explanations by generating and testing hypotheses in a series of substudies. We moved from the epidemiological to the neurobiological and finally to the clinical level. The present article is an attempt to provide a brief overview of the individual stages of the ABC study and the different levels of investigation involved in formulating and testing the estrogen hypothesis in animal experiments and in demonstrating its applicability to human schizophrenia. From these results, three hypotheses were formulated and tested on data from an ABC study sample of 232 first-episode cases of schizophrenia. The analyses described here represent the latest stages of the ABC study.

Adolescent↗

PubMed1997

Epidemiology of schizophrenia.

OBJECTIVE: To characterize the epidemiology of schizophrenia. METHOD: Narrative literature review. RESULTS: Each year 1 in 10,000 adults (12 to 60 years of age) develops schizophrenia. Based on a restrictive and precise definition of the diagnosis and using standardized assessment methods and large, representative populations, the incidence rates appear stable across countries and cultures and over time, at least for the last 50 years. Schizophrenic patients are not born into ecological and social disadvantage. The uneven distribution of prevalence rates is a result of social selection: an early onset leads to social stagnation, a late onset to descent from a higher social status. The main age range of risk for schizophrenia is 20 to 35 years. It is still unclear whether schizophrenia-like late-onset psychoses (for example, late paraphrenia) after age 60 should be classified as schizophrenia either psychopathologically or etiologically. In 75% of cases, first admission is preceded by a prodromal phase with a mean length of 5 years and a psychotic prephase of one year's duration. On average, women fall ill 3 to 4 years later than men and show a second peak of onset around menopause. Consequently, late-onset schizophrenias are more frequent and more severe in women than in men. The sex difference in age of onset is smaller in cases with a high genetic load and greater in cases with a low genetic load. Type of onset and core symptoms do not differ between the sexes. The most pronounced sex difference is the socially negative illness behaviour of young men. CONCLUSIONS: Among the factors determining social course and outcome are level of social development at onset, the disorder itself (for example, genetic liability, severity of symptoms, and functional deficits), general biological factors (for example, estrogen), and sex- and age-specific illness behaviour.

Adolescent↗

PubMed1996

[Can outpatient measures prevent inpatient admission?].

During the last decades the focus of psychiatric care has shifted from hospital to the "community". As the philosophy of deinstitutionalisation implies that community mental health care is preferable to hospital care and that treatment functions may be performed equally well or even better outside a hospital, one of the main objectives of community-based care consisted in preventing hospital readmission. Despite many objections readmission data and length of stay become most popular as outcome criteria in the evaluation of treatment measures. However, until today evaluative research has failed to demonstrate the overall effectiveness in preventing inpatient treatment. This is mainly due to the fact that the complexity of the research topic could not be adequately modelled and controlled in observational studies as the main source of information.

Chronic Disease↗

PubMed1995

When and how does schizophrenia produce social deficits?

The present study is an empirical contribution to the controversy over whether the poor social performance and lower social class of schizophrenic patients are consequences of the illness, consequences of changes in the individuals predisposed to develop schizophrenia or are due to the adverse social conditions that lead to schizophrenia. The study focuses on the socioeconomic status at onset, on the performance of social roles in the early course of schizophrenia by taking age, gender and the individual level of social development into account. In a representative sample of 232 first episodes of schizophrenia age and type of onset.type and accumulation of symptoms and social functioning in the prodromal and the psychotic prephase and at first admission were assessed and analysed for their predictive power concerning social disability 2 years after first admission. In a case-control study expected and observed social functioning from onset until first admission were compared. The subsequent course was followed up prospectively in five cross sections until 2 years after first admission. In women the age at onset was significantly higher than in men, whereas symptomatology and type of onset showed no gender differences. In 73% of the sample the prodromal phase covered 5 years on average, and the psychotic prephase (until the maximum of positive symptoms) 1.1 years. Deficits in social functioning occurred predominantly during the prodromal and the psychotic prephase. The course over 14 years showed stable group trends in social and symptom measures. By the end of the prodromal phase it was possible to predict social disability 2 years after first admission with a correct classification of 81%. The main factor determining social outcome appeared to be the acquired social status during the prodromal phase of the disorder. The unfavourable early course in men was due mainly to their significantly lower age at onset. These results raise questions concerning an earlier therapeutic and rehabilitative intervention.

Adolescent↗

PubMed1995

New perspectives in the epidemiology of schizophrenia.

It was with great pleasure that I accepted the invitation to contribute to the present symposium in honour of my friend Jules Angst. It gives me the opportunity to pay tribute to his outstanding scientific work. The topic of my presentation has been inspired by the genius loci. In his foreword to a proceedings volume entitled 'Die Entstehung der Schizophrenie' (The Origin of Schizophrenia), which he edited on the occasion of the 100th anniversary of the Psychiatric University Hospital Zurich in 1970, Jules Angst pointed out that two former heads of the 'Burgholzli', Eugen and Manfred Bleuler, who had held that office longest, had dedicated their life's work to schizophrenia, which had received its name from Eugen Bleuler. Jules Angst's most successful research field has been psychiatric epidemiology. I therefore thought it appropriate to talk about new perspectives in the epidemiology of schizophrenia.

Adult↗

PubMed1995

[The Mannheim long-term study of schizophrenia. Initial results of follow-up of the illness over 14 years after initial inpatient treatment].

A 14-year follow-up was accomplished on 56 out of a total of 70 patients first admitted to hospital with Schneiderian first-rank symptoms. Data collected during 5 years after index admission were also at our disposal. Three quarters of the probands are living alone, and barely one third are in regular employment. At the time of the 14-year follow-up about one third showed delusions or hallucinations. Almost the same number had psychological impairments and 64% were socially disabled. Comparison with the data collected at 1 year and 5 years reveals no difference in the rates of impairments and symptomatology, but a significant increase of social disability.

Adult↗

PubMed1994

The epidemiology of early schizophrenia. Influence of age and gender on onset and early course.

For the investigation of the early course of schizophrenia starting from onset, the standardised Interview for the Retrospective Assessment of the Onset of Schizophrenia was developed and validated. In a representative sample of 267 first-admitted German schizophrenics of a broad diagnosis from a population of 1.5 million, the age at which different diagnostic and onset definitions were satisfied, the symptoms at the time of the interview, and the accumulation of positive and negative symptoms until first admission were assessed. Comparison between the two sexes and three age groups yielded hardly any differences in the accumulation of symptoms and their course until first admission, except for a slightly shorter period of negative symptoms in young males and a slightly longer one in older women--which contradicts prevailing opinion. At the time of the interview, no significant sex differences were found with respect to the core symptoms of schizophrenia (negative and first-rank symptoms), but clear and substantial differences emerged in disease behaviour. The significantly higher age at first onset in women is explained, on the basis of animal experiments and a clinical study, by the neuromodulatory effect of oestrogen on D2 receptors and by a higher vulnerability threshold in women.

Adolescent↗

PubMed1993

[A chapter in systematic schizophrenia research--the search for causal explanations for sex differences in age of onset].

With the aim of detecting causal processes contributing to the onset of schizophrenic symptoms a systematic search strategy was worked out. One of the few epidemiological findings on schizophrenia consistently diverging from expected values, the sex difference in age at first admission, was taken as a basis and replicated on data from the Danish and the Mannheim case registers by controlling for selection and diagnostic artefacts. Danish psychiatrists turned out to have underdiagnosed schizophrenia to a considerable extent at least in 1976, the year from which the analysed case-register data dated. After the exclusion of alternative explanations, the time when symptoms appeared for the first time and the first acute episode occurred was determined for a representative sample of 267 first-admitted cases with a diagnosis of non-affective functional disorder by using the IRAOS interview designed for this purpose. At any of the definitions of first onset applied the mean age of females was significantly higher than that of males, the difference ranging from 3.2 to 4.1 years. The distribution of onsets across the female life cycle showed a clearly delayed increase at young age and a second, lower peak of onsets at the age of 45-54, whereas the cumulative incidence up to the age of 60 years was equal for males and females. On assessing the plausibility of psychosocial versus biological explanations it was hypothesized that due to the effect of estrogens the vulnerability threshold for schizophrenia is raised in females until the menopause. Animal experiments and postmortem analysis showed that chronic estrogen applications significantly shortened dopamine-induced behaviour and reduced D2 receptor sensitivity in the brain. The applicability of this pathophysiological mechanism on human schizophrenia was tested on acutely schizophrenic females with normal menstrual cycles. A significant negative correlation was found between measures of symptomatology and plasma estrogen levels. Apparently, the manifestation of schizophrenic symptoms is influenced by a sufficiently sensitive D2 receptor system in the brain, blocked by neuroleptics and modulated by estrogens.

Adolescent↗

PubMed1991

The course of schizophrenia: some remarks on a yet unsolved problem of retrospective data collection.

The retrospective assessment of symptoms and syndromes is a basic measure in research of the longitudinal course of schizophrenia. In spite of its importance there have been few studies evaluating the standard of quality of instruments for retrospective data collection. Combining retrospectively and cross-sectionally collected data on schizophrenic symptomatology in a cohort study over a period of 5 years revealed a significant underestimation of symptoms when assessed in retrospect. The need for studies on the validity of instruments for the retrospective assessment of symptoms is stressed.

Delusions↗

PubMed1991

[Sex differences in schizophrenic diseases].

Sex differences in schizophrenic diseases have been known for a long time but have also been subject to long-term neglect by psychiatric epidemiological research, although a study of these sex differences could, in our opinion, yield valuable pointers to pathogenic factors involved in this group of diseases the aetiology of which still awaits clarification. For this reason we initiated large-scale investigations focussed on this topic. The paper presented here discusses a few initial results, basing on data of Mannheim and National Danish Case Records and on our own study on schizophrenia, the latter being a representative record of 392 patients hospitalised for the first time in the Rhine-Neckar region and the eastern part of the Palatinate. First of all, sex differences at the age at which the disease appeared for the first time, were studied while paying close attention to artifacts and other, usually neglected methodical error sources. The difference in the average age of the sexes at first hospitalisation was confirmed, and also--using an instrument specially developed for that purpose--at the onset of the disease. At the time the first signs of the disease are noticed and the first schizophrenic symptoms become apparent, men are about 3 to 4 years younger than women. On the other hand, the cumulative lifetime risk--calculated up to 60 years of age--seems to be the same for both sexes. It appears that there are no sex differences in the pattern of symptoms of the disease at the time of initial hospital admittance, in respect of both the most common and the characteristic signs and symptoms. There were significant although quantitatively not very great differences in respect of patient behaviour which displays socially positive aspects somewhat more often in women and socially negative ones distinctly more often in men. In respect of the course of the disease we could not find any marked sex differences over a period of 10 years after onset of the disease; however, this is presently based only on the Danish case record data and on criteria of the course of the disease, such as number and duration of inpatient treatments.

Adolescent↗

PubMed1991

Evaluating effectiveness and cost of community care for schizophrenic patients.

The two main types of mental health services research are (1) the evaluation of the mental health sector within comprehensive systems of health care and (2) the evaluation of individual mental health facilities or types of care. Depending on the information systems available, the difficulties of evaluating complex systems of care can be partially obviated by using descriptive approaches. Structural quality can be assessed by structural indices, the functioning of a system by monitoring utilization, and the overall effectiveness of a national mental health care system roughly by health indicators. Causal analyses of effectiveness are practical when they are based on individual facilities or types of care, which can be studied as isolated systems on the basis of intervention and outcome variables. Reliable and reproducible results can be achieved only if a standardized intervention is used or if the intervention and its objectives are described clearly, the output indicators are defined in terms of identifiable and repeatable operations. The assets and liabilities of quasi-experimental designs and three types of naturalistic approaches will be discussed. When the cost of a new type of care is compared with the cost of traditional mental health care, the section of the population actually served out of the total of patients with comparable needs for care should be considered. Results from the authors' studies will show how the neglect of this epidemiological aspect can lead to false statements.

Activities of Daily Living↗