Epidemiology of schizophrenia. A thriving discipline at the turn of the century.
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Cross-Sectional Studies↗
Biomedical subjects
H Häfner
Publications and source records attributed to H Häfner.
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↗
Gender aspects in schizophrenia: bridging the border between social and biological psychiatry.
OBJECTIVE: This paper tries to show that gender differences in mental diseases are a valuable paradigm for research into the interplay between biological and psychosocial factors--not only regarding pathogenetic mechanisms, but also concerning therapeutic approaches. METHOD: Based on relevant literature, this topic is highlighted using schizophrenia as an example. RESULTS: Schizophrenic disorders show a later age of onset in women and a slightly better course, especially in young women. As to pathogenesis, there is some evidence that the age difference might be due at least partly to the female sex hormone oestradiol being a protective factor. Differences in course might also have to do with this biological factor, but at the same time with the psychosocial advantages of a higher age of onset and other psychosocial factors. Concerning therapy, these gender differences have important implications for pharmacotherapy, but also psychotherapy and social measures. CONCLUSION: A gender-sensitive approach in psychiatry improves our understanding of mental illness and our therapeutic strategies and at the same time illustrates that comprehensive psychiatry cannot be practised in artificially separated 'drawers' called 'biological psychiatry', on one hand, and 'social psychiatry' on the other.
Adult↗
[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↗
Cannabis, vulnerability, and the onset of schizophrenia: an epidemiological perspective.
OBJECTIVE: Second to alcohol, cannabis is the most frequently misused substance among patients with schizophrenia. The aim of this paper is to examine at early onset of psychosis whether the high comorbidity of schizophrenia and cannabis abuse is due to a causal relationship between the two disorders. Previous studies have mostly included chronic patients or samples with mixed stages of the psychotic illness. METHOD: In a German catchment area with a population of 1,500,000, a representative first-episode sample of 232 patients with schizophrenia was included in the Age, Beginning and Course of Schizophrenia Study. By means of a structured interview, the Retrospective Assessment of the Onset of Schizophrenia, the onset and course of schizophrenic symptoms and of substance abuse was systematically assessed retrospectively. Information given by relatives validated the patients' reports. RESULTS: Thirteen per cent of the sample had a history of cannabis abuse, which was twice the rate of matched normal controls. Male sex and early symptom onset were major risk factors. While cannabis abuse almost always preceded the first positive symptoms of schizophrenia, the comparison of the onset of cannabis abuse and of the first (prodromal) symptoms of schizophrenia differentiated three approximately equal groups of patients: group 1 had been abusing cannabis for several years before the first signs of schizophrenia emerged, group 2 experienced the onset of both disorders within the same month, and group 3 had started to abuse cannabis after the onset of symptoms of schizophrenia. CONCLUSIONS: The vulnerability-stress-coping model of schizophrenia suggests possible interpretations of these findings. Group 1 might suffer from the chronic deteriorating influence of cannabis reducing the vulnerability threshold and/or coping resources. Group 2 consists of individuals which are already vulnerable to schizophrenia. Cannabis misuse then is the (dopaminergic) stress factor precipitating the onset of psychosis. Group 3 uses cannabis for self-medication against (or for coping with) symptoms of schizophrenia, particularly negative and depressive symptoms. These patients probably learn to counterbalance a hypodopaminergic prefrontal state by the dopaminergic effects of cannabis. The implications of these very preliminary results include issues of treatment and prognosis, but replication studies are needed.
Adaptation, Psychological↗
Onset and early course as determinants of the further course of schizophrenia.
OBJECTIVE: First treatment contact is preceded by a lengthy prodromal and psychotic prephase. We analysed the occurrence of symptoms and disabilities prior to first contact and their consequences for medium-term illness course. METHOD: A population-based sample of 232 first episodes of schizophrenia was studied retrospectively using the IRAOS and compared with matched peers from the population of origin. Further illness course was studied prospectively at six cross-sections over 5 years from first admission onwards. RESULTS: Three quarters showed a prodromal phase of 5 years (mean) and a 1-year accumulation of psychotic symptoms. First to appear were depressive and negative symptoms and early signs of cognitive and social impairment. Social disability emerged 4 to 2 years before first contact. Further illness course was determined by stage of social development at psychosis onset with the consequence of a significantly poorer course for men than women because of men's earlier illness onset. Symptomatology, type of onset, age and gender influenced social course via stage of social development and, additionally, via young men's socially adverse illness behaviour. CONCLUSION: Social course is determined by individual stage of social development at illness onset and by early illness course. Therefore, early detection and intervention are needed.
Adult↗
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↗
[Dimensions of schizophrenic symptomatology. Comparative testing of several theoretical models in a first-episode population sample].
The issue of this study was the investigation of the dimensional structure of non-psychotic and psychotic symptoms in 232 first-episode schizophrenic patients (ICD-9 295., 297., 298.3, 298.4). The study was conducted within the ABC-Schizophrenia-Study. The three-factor-model of Liddle with three factors (psychomotor poverty, disorganisation, reality distortion) was replicated for the time at first admission. The model is also valid for first-episode-patients as well as to chronic patients. The comparison of the three-factor-model of Liddle with Crow's dual process model, Andreasen's bipolar model and the "severity-liability" model was done by means of confirmatory factor analysis. The comparison shows that at first admission, the three-factor-model fitted in best with the data. In contrast to previous analyses within the ABC-Study, in which positive correlations have been found between positive and negative symptoms, no positive correlation exists between Liddle's negative and positive dimensions. This may be the consequence of the subdivision of the positive dimension into the two dimensions disorganisation and psychotic symptoms. As within the three-factor-model only the negative dimension and disorganisation correlated weekly, the three dimensions are best viewed as relatively independent for the time at first admission. There are no associations between sex, type of onset, age at onset and the three dimensions of Liddle's model. Patients with the familial load are more disorganized and patients with obstetric complications show more negative symptoms. While the negative dimension shows a high stability over five years, the dimensions "disorganisation" and "positive symptoms" are not stable over time. However, there is a high degree of correlation for the dimensions "disorganization" and "positive symptoms" among cross-sections while the negative dimension was independent of the other two dimensions. The negative dimension is a highly significant predictor for social disability and social development over five years, whereas the dimensions "disorganization" and "positive symptoms" have no prognostic importance for the outcome in the long term.
Acute Disease↗
Ecological pattern of first admitted schizophrenics in two German cities over 25 years.
Ecological studies on the distribution of rates of first-admitted schizophrenics were carried out in Mannheim in 1965 and from 1974 to 1980. As the catchment area of the ABC Schizophrenia Study comprises the cities of Mannheim and Heidelberg, we were able to conduct a third ecological study for Mannheim and a first study for Heidelberg covering the years 1987 to 1989. High rates of schizophrenic residents are found in the inner districts of Mannheim and Heidelberg. This concentration has been stable over a period of 25 years for Mannheim. Subdividing the districts of Mannheim and Heidelberg into zones, only in Heidelberg and only for the second cross-section in Mannheim, the rates decreased constantly with increasing distance from the centre. Summing up the districts of Mannheim and Heidelberg in homogenous areas on the basis of economical and socio-demographic properties, high rates of schizophrenics were found in homogenous areas with poor and unfavourable living conditions. In Mannheim and Heidelberg, homogenous areas with the highest rates of schizophrenics are characterised by highly unfavourable living conditions, a high percentage of young men, people living alone, students, foreigners, people with a low level of education and a high immigration/emigration rate. The analysis on the individual level, i.e. in the biography of schizophrenics shows that processes of social drift and/or nonstarter take place long before first admission in the prodromal phase and the psychotic prephase of beginning schizophrenia. Probably, these selective processes like downward drift or nonstarting processes, lead to the migration of schizophrenics into unfavourable areas or schizophrenic residents staying in poor areas, while healthy residents leave these districts. Selective processes such as help seeking behaviour and access to the care system have no effect on the unequal distribution. In summary, a definite confirmation or refutation of one of the two causal hypotheses, 'social selection' vs. 'social causation', is not possible up to date, but the empirical results support the selective hypothesis for schizophrenic disorders.
Adolescent↗
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↗
The stress inducer arsenite activates mitogen-activated protein kinases extracellular signal-regulated kinases 1 and 2 via a MAPK kinase 6/p38-dependent pathway.
Cell response to a wide variety of extracellular signals is mediated by either mitogenic activation of the Raf/MEK/ERK kinase cascade or stress-induced activation of the mitogen-activated protein kinase (MAPK) family members c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) or p38. We have examined communications between these stress- and mitogen-induced signaling pathways. We show here that the stress cascade activator arsenite activates extracellular signal-regulated kinase (ERK) in addition to p38 albeit with different kinetics. Whereas p38 is an early response kinase, ERK activation occurs with delayed time kinetics at 2-4 h. We observed activation of ERK upon arsenite treatment in many different cell lines. ERK activation is strongly enhanced by overexpression of p38 and mitogen-activated protein kinase kinase 6 (MKK6) but is blocked by dominant negative kinase versions of p38 and MKK6 or the specific p38 inhibitor SB203580. Arsenite-induced ERK activation is mediated by Ras, Raf, and MEK but appears to be independent of de novo protein synthesis. These data provide the first evidence for a p38 dependent activation of the mitogenic kinase cascade in stress-stimulated cells.
Arsenites↗
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↗
Is schizophrenia a disorder of all ages? A comparison of first episodes and early course across the life-cycle.
BACKGROUND: The heterogeneity of schizophrenic and delusional syndromes by age of onset has frequently been discussed. METHODS: The age distribution of symptoms and 5 year course was studied in a population-based first-episode sample admitted to 10 psychiatric hospitals before the age of 60 (N = 232) and in a clinical sample without age limit of consecutive first admissions to a single hospital (N = 1109), both samples with broadly diagnosed schizophrenia. RESULTS: Early-onset patients, particularly men, presented more non-specific symptoms and higher PSE-CATEGO total scores than late-onset patients. In men, symptom severity decreased with increasing age of onset. In women, it remained stable except for an increase of negative symptoms with late-onset. Only a few symptoms changed markedly with age: disorganization decreased, while paranoid and systematic delusions increased steeply across the whole age of onset range. Pronounced age- and sex-differences emerged in illness behaviour, socially negative behaviour and substance abuse. Within the group of late-onset psychoses there were continuous transitions in symptom profiles and no discrimination between schizophrenia and paranoid psychosis or late paraphrenia. The main determinant of social course was onset level of social development. Early-onset patients did not improve in social status, while late-onset patients, prior to retirement, suffered considerable decline in social status. CONCLUSIONS: Gender differences in age at onset and in age trends in symptom severity support the hypothesis of a mild protective effect of oestrogen. Social course results from an interplay between biological factors (age at onset and functional impairment) and development factors (level of social development at onset and illness behaviour).
Adolescent↗
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↗
Late-onset schizophrenia and the delusional disorders in old age.
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Age of Onset↗
[Reliability of family reports of illness anamnesis of schizophrenic patients].
Because a valid psychiatric history is difficult to obtain from an acute psychotic patient, particularly upon first admission, information given by important others is necessary for diagnostic classification, but the validity of this data must be examined. Within the ABC Schizophrenia Study, the onset and early course of schizophrenia was assessed from 171 post-psychotic first admissions and their close relatives. High agreement was found for substance abuse, self-destructive behaviour, paranoid delusion and social role deficits. Agreement was low for unspecific symptoms like depression, anxiety, problems with concentration or sleep. Due to a lack of sensitivity of the relatives' reports, agreement was also low for formal thought and perceptual disorders and derealization. A second study with 30 patients with schizophrenia and with 2 or more relatives for each case (n = 69) demonstrated that the quality of relatives' reports depends primarily on the relative's image of the patient (e.g., perceived dominance) and on the relative's attributions about the cause of the disease. Close and long contact tends to impair the quality of reports. Again, the observation of different symptoms is influenced differently by these factors.
Adolescent↗
Sensitivity and specificity of relatives' reports on the early course of schizophrenia.
Within the ABC Schizophrenia Study, a large-scale investigation of the influences of age and gender on schizophrenia, the retrospective reports on emerging psychopathology during the early course of schizophrenia given by 171 post-psychotic patients and their significant others were compared in a representative first-admission sample by means of the Interview for the Retrospective Assessment of the Onset and Early Course of Schizophrenia. High agreement (kappa) between patients and relatives was found for substance abuse, suicidal behaviour, parental and marital role deficits, and paranoid delusions. Low positive agreement rates (sensitivity) were seen for perceptual and formal thought disorders. Low negative agreement rates (specificity) were found for depression, anxiety, and similar "unspecific' symptoms. Relatives' reports are helpful but should be used with caution.
Adult↗
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↗