Biomedical subjects

H Häfner

Publications and source records attributed to H Häfner.

At least 73 records · Page 4Linked to original sources

PubMed1994

Can estradiol modulate schizophrenic symptomatology?

Using epidemiologic data, in an earlier study we formulated the hypothesis that estrogens can delay the onset of schizophrenia in females by raising the vulnerability threshold for this disease. In animal experiments, Häfner and colleagues found evidence that chronic estradiol treatment reduces the sensitivity of dopamine (D2) receptors in the brain. In the clinical study presented in this article, as a further step we examined the antipsychotic properties of estradiol in human females by testing whether schizophrenic symptomatology varies with estradiol serum levels throughout the menstrual cycle. We examined 32 acutely admitted female schizophrenia patients (Present State Examination/CATEGO diagnosis, ICD-9) with a history of regular menstrual cycles, ages 18 to 43 (mean = 30.5), during their hospital stays (3-8 weeks), analyzing hormonal parameters and applying various rating scales for psychopathology every 7 days. In all patients, estradiol serum levels were markedly reduced as compared with the normal population, and fluctuations throughout the cycle were dampened. Nevertheless, a significant association emerged between estradiol levels, on the one hand, and psychopathology scores, on the other--that is, the psychiatric symptomatology as assessed by the clinical psychiatrist (Brief Psychiatric Rating Scale, p < or = 0.01), behavior on the ward as assessed by the nursing staff (Nurses' Observation Scale for Inpatient Evaluation p < or = 0.01), paranoid tendencies and general well-being as assessed by the patients themselves (Paranoid-Depressivitäts-Skala paranoid score p < or = 0.05; Befindlichkeits-Skala p < or = 0.05). Psychopathology seems to improve when estradiol levels rise, and vice versa. These findings can be interpreted as further evidence for a protective effect of estrogens in schizophrenia, possibly due to the known anti-dopaminergic activities of these hormones.

Adolescent↗

PubMed1994

Validation of Danish case register diagnosis for schizophrenia.

The ABC schizophrenia study aims at investigating sex differences in age of onset, symptoms and course of schizophrenic and paranoid disorders. For this purpose, we used case register data from Denmark and Mannheim and a directly examined sample of first admissions (ABC sample). The Danish case register sample included less clinical diagnoses of schizophrenia and more schizophrenia-related disorders (acute paranoid reaction, paranoid states and borderline schizophrenia) than the Mannheim data (case register and ABC sample). The problem therefore was whether the two datasets are comparable and the results are valid. For this reason a randomized, stratified sample of 116 patients was drawn from the Danish case register sample. The case notes of these 116 patients were requested from the hospitals where the patients had been treated and analyzed by means of a scoring sheet based on the Interview for the Retrospective Assessment of the Onset of Schizophrenia (IRAOS). The use of operationalized diagnoses of the CATEGO program, based on PSE items, which are integrated in IRAOS, demonstrated that the samples of the Danish and the Mannheim case registers and the directly investigated ABC sample have comparable diagnostic distributions. Possible explanations for the differences between the clinical and the CATEGO diagnoses in the Danish case register may be the frequent use of diagnoses of borderline schizophrenia and reactive psychoses (previously called psychogenic psychoses), and above all a more narrow concept of schizophrenia; in Denmark, schizophrenia is diagnosed relatively late, i.e., after the presence of enduring negative symptoms, and thus mostly after the appearance of residual state.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

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

Schizophrenia and oestrogens--is there an association?

Some early psychiatrists already believed that schizophrenic disorders were associated with a disturbed balance of sexual hormones. This belief was based on the observation of a. an "insufficient functioning of the sexual glands" with so-called "hypoestrogenism", and b. an influence of ovarian function on schizophrenic psychoses. As this review shows, there are findings from recent research which seem to confirm that estrogens may have a protective effect in schizophrenia. There are also occasional hints at a possible "hypoestrogenism" in schizophrenia. In our own epidemiological, clinical and animal studies the hypothesis of a protective effect of oestrogens was for the first time systematically examined and confirmed. Oestrogens seem to modulate the sensitivity of D2-receptors in the brain, and clinically they seem to have a neuroleptic-like effect. These findings may have important implications for the prevention and therapy of schizophrenic disorders. Furthermore, our findings indicate the need to reinvestigate the question of a disturbed balance of sexual hormones in schizophrenic disorders. Further research on the role of oestrogens in schizophrenic disorders could in our opinion contribute to understanding the still unclear, possibly aetiologically heterogeneous pathogenetic mechanism of schizophrenic psychoses.

Age Factors↗

PubMed1993

Evidence for a gender bias in epidemiological studies of schizophrenia.

A higher lifetime morbidity risk for schizophrenia in males has been observed by several investigators. Studies controlled for errors in patient selection and other sources of artefacts, however, find an equal risk in both sexes. In order to detect the causes for the underrepresentation of women in many studies, sample composition of multicentre WHO studies was analysed. Severity of symptoms was not found to be responsible for imbalances in the male/female ratios, but cultural influences and design characteristics were: due to the scarcity of psychiatric facilities, women are less likely to receive adequate treatment in most of the developing countries investigated, since they are kept longer at home and seen by traditional healers in some cultures. Also, studies with an upper age limit of 44 years (according to DSM-III) exclude a greater proportion of female than male schizophrenic patients, and there is some evidence that schizophrenia is more often underdiagnosed in women than in men at least in some countries. Implications for future research on gender differences in schizophrenia are discussed.

Adult↗

PubMed1993

Generating and testing a causal explanation of the gender difference in age at first onset of schizophrenia.

Motivated by the lack of knowledge of the pathophysiological processes underlying the manifestation of symptoms in schizophrenia, we have worked out a systematic search strategy. Since epidemiological distribution patterns consistently deviating from expected values provide valuable indications of causal relationships, we chose the higher age of females at first admission for schizophrenia, first reported by Kraepelin and since then confirmed in over 50 studies, as the basis for our study. This unexplained epidemiological finding was replicated on Danish and Mannheim case-register data by systematically controlling for selection and diagnostic artefacts and by testing alternative explanations at the individual stage of the study. To check whether the difference in age at first admission was determined by a difference in age at onset, a representative sample of 267 first-admitted patients with non-affective functional psychosis was examined by using an interview for the retrospective assessment of the onset of schizophrenia (IRAOS) designed for this purpose. Any of the definitions of first-ever onset applied--first sign of mental disorder, first psychotic symptom, first acute episode--led to a significant age difference of 3.2 to 4.1 years between the sexes. The distribution of onsets across the life cycle showed a later increase and a second, lower peak between the ages of 45 and 54 years among females compared with males. The lifetime risk for schizophrenia was equal for males and females. After testing the plausibility of psychosocial versus biological explanations we hypothesized that due to the effect of oestrogens the vulnerability threshold for schizophrenia is elevated in females until the menopause. Animal experiments and post mortem analyses showed that chronic oestrogen applications significantly shortened dopamine-induced behaviour and reduced D2 receptor sensitivity in the brain. The applicability of this pathophysiological mechanism to human schizophrenia was tested on acutely schizophrenic females with normal menstrual cycles. A significant negative correlation was found between measures of symptomatology and plasma oestrogen levels. The manifestation of symptoms in schizophrenia appears to be influenced by a sufficiently sensitive D2 receptor system in the brain, blocked by neuroleptics and modulated by oestrogens.

Age Factors↗

PubMed1993

["Trema, apophany, apocalypse"--is Conrad's phase model empirically founded?].

Among several phase models of beginning schizophrenia, the study by Conrad ("Die beginnende Schizophrenie. Versuch einer Gestaltanalyse des Wahns") was particularly impressive in German psychiatry. The ABC-Schizophrenia-study with its representative sample of 267 first-admissions and a careful retrospective assessment of emerging symptomatology made it possible to test the empirical basis of Conrad's model. In this operationalization "trema" was confirmed as the frequent first stage of the disease process, whereas Conrad's hypothesized order of the two following phrases (first "apophany", then "apocalypse") could not be validated. Therefore, Conrad's model cannot completely be generalized. Because the methods employed so far have some limitations, analyses of additional data (especially reports by significant others) may control and probably enhance the presented results.

Adolescent↗

PubMed1993

The influence of age and sex on the onset and early course of schizophrenia.

A new standardised interview for the retrospective assessment of onset and early course of schizophrenia (IRAOS) was used to study the influence of age and sex on time of onset and psychopathology before first admission in 267 schizophrenic patients admitted for the first time. Mean age at onset, according to various operationalised definitions, differed by three to four years between the sexes. The age distribution at the earliest sign of mental disorder showed an early and steep increase until the age of 25 in males, and a delayed and smaller increase in females, with a second peak in women aged 45-79. Schizophrenia began with negative symptoms in 70% of cases, appearing two to six years before admission, and all positive symptoms appearing up to two years before. Both positive and negative symptoms accumulated exponentially. The early course of the disease was similar across age groups, except there was a longer period of negative symptoms before first admission in late-onset schizophrenia in women. The few significant age differences in symptoms were presumably due to general age-dependent reaction patterns like anxiety and depression or the cognitive development of personality, as indicated by an increase in fully elaborated positive symptoms, especially systematised paranoid delusions, with age.

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↗

PubMed1992

Gender differences in schizophrenia in three cultures. Results of the WHO collaborative study on psychiatric disability.

As part of a systematic research project on the influence of gender factors on age at onset, symptomatology, and course of schizophrenia, data on gender differences in age at onset and symptomatology of schizophrenia from the WHO Collaborative Study "On Assessment and Reduction of Psychiatric Disability" were compared between seven research centres of three different cultural regions. Results on age at onset of five European centres confirmed the well known fact of an earlier onset in men. The earlier onset in women seen in Khartoum and Ankara could be attributed to patient selection because male/female differences in age at onset and male/female ratios in the various samples covary. In the Islamic centres no relevant gender differences in real age at onset and in symptomatology could be detected as probable causes of earlier hospitalisation of women. Major gender differences in symptomatology were found in the Balkan centres of Sofia and Zagreb with a high prevalence of delusional symptoms in women and depression in men. In Western Europe centres, nuclear schizophrenic symptoms were equally prevalent in either sex, while nonspecific symptoms like irritability and tiredness (more frequent in women) and maladaptive illness behaviours like alcohol abuse and social withdrawal (more frequent in men) differed between the sexes. Explanatory hypotheses and the implications of these results are discussed.

Adult↗

PubMed1992

Is age of onset in schizophrenia influenced by marital status? Some remarks on the difficulties and pitfalls in the systematic testing of a "simple" question.

Schizophrenia is a disease characterized by a distinctly higher age at onset and at first admission in females than in males. In a systematic study on gender differences in schizophrenia we have confirmed this finding using different sets of data, in particular through the examination of a large and representative sample of first-admitted patients. The question addressed in this paper is whether marital status influences this sex-specific age difference. Assuming that marriage or a stable relationship is a protective factor in schizophrenia, delaying the onset of the disease or first hospitalization, the hypothesis was formulated that the later age of onset in women is at least partly explained by their generally earlier age of marriage. Testing this hypothesis illustrates some of the methodological problems that often occur when a causal analysis of social data is attempted. The problems emerge especially when both the dependent variable (age of onset/first admission) and the independent variable (marital status) are essentially related to age. First results appearing to indicate an influence of marital status on age at first admission did not bear a critical interpretation.

Adolescent↗

PubMed1992

The high incidence of psychiatrically treated disorders in the inner city of Mannheim. Susceptibility of German and foreign residents.

In earlier investigations in the city of Mannheim we examined the spatial distribution of the incidence of treated mental disorders in 1965 and 1974-80. In studying the ecology of psychiatric disorders over time, it is important to consider major demographic developments. In Mannheim between the mid-sixties and 1980 the most striking demographic change was the increase of foreign residents, whose proportion almost trebled during this period. In this study we test the hypothesis whether the excess morbidity in the inner city where housing conditions are relatively poor and the percentage of foreign residents is far above average can be explained by the high proportion of immigrants, mainly from Turkey, living there. Due to motivational and administrative factors, most immigrant workers being recruited on the basis of good physical and mental health, the age-adjusted incidence of treated psychiatric disorders between 1974 and 1980 among the German population exceeded that of foreign residents. The high concentration of psychiatric disorders in the inner city is due solely to the German and not to the foreign residents. The most plausible explanation for this is provided by the segregation hypothesis. Individuals with vulnerable personalities tend to move to socially disorganized districts of the city. Furthermore, the health status of those Germans who left areas of poor environmental conditions was probably better in comparison to those who remained in the inner city.

Cross-Cultural Comparison↗

PubMed1992

Transnational stability of gender differences in schizophrenia? An analysis based on the WHO study on determinants of outcome of severe mental disorders.

Gender-specific analyses of the multinational WHO-Determinants of Outcome-Study (including 1,292 cases from 10 countries) demonstrate the transnational stability of major findings on gender differences in schizophrenia: Male patients have an earlier mean age at onset in all countries. In female patients, the distribution of the age at onset shows a second peak after age 40 years. No gender differences on nuclear symptoms of schizophrenia can be detected, but on uncharacteristic symptoms, particularly some aspects of the illness behaviour, differences appear. This investigation supports the transcultural validity of gender differences found in the German ABC-Schizophrenia-Study and in the Danish-German Psychiatric Case Register studies.

Adult↗

PubMed1992

First onset and early symptomatology of schizophrenia. A chapter of epidemiological and neurobiological research into age and sex differences.

In the frame of the ABC (Age, Beginning and Course) Schizophrenia Project we studied the influence of age and sex on first-ever onset, symptom manifestation and early course up to first admission in schizophrenia by using a large, representative sample of first-admitted schizophrenic patients. The results showed that the two variables had surprisingly little bearing upon the core symptoms, particularly on negative and other most frequent symptoms and on first-rank symptoms. In 70% of the cases schizophrenia started solely with negative symptoms, in 20% with negative and positive and in 10% with positive symptoms only. In most of the cases symptoms accumulated exponentially up to the first acute episode with positive symptoms appearing considerably later. The age differences observed concerned secondary phenomena associated with developmental factors. Such phenomena, i.e. anxiety, depression and the cognitive formation of delusions, can be interpreted as responses to the psychosis. Also the sex differences, which culminated in far more frequent socially negative disease behaviour in males, were limited to secondary phenomena. This positive and negative core symptomatology of schizophrenia seems to be astonishingly uniform and fairly independent of age and sex at this early stage of the disease. The only remarkable difference was a three to four years higher mean age of onset in females. We were able to show in animal experiments and to confirm in a clinical study that this finding is attributable to a neuromodulatory effect of estrogens on the sensitivity of D2 receptors in the brain. Apparently, estrogens raise the vulnerability threshold until menopause and have a slight neuroleptic-like effect on the symptomatology in acute schizophrenic episodes.

Adolescent↗

PubMed1992

IRAOS: an instrument for the assessment of onset and early course of schizophrenia.

Since Kraepelin's first description of dementia praecox in 1889 many data and theories have been published on the onset and course of schizophrenia. Until now studies on these topics had to rely on first admission data and on the subsequent course of the disease. However, first hospitalisation is preceded by a wide variety of patterns and duration of the early course. Items taken from the pre-admission phase of the disease are often incorrectly used as premorbid characteristics, understandably preceding the subsequent course and outcome of schizophrenia with high predictive power. In relation to our interest to study the beginning of schizophrenia, systematically, paying special attention to the age and gender distribution of true onset and the symptomatology and pattern of the early and later course, we developed an 'Interview for the Retrospective Assessment of the Onset of Schizophrenia (IRAOS)'. It allows an objective, reliable, and valid assessment of the symptoms, psychological impairments, demographic and social characteristics as well as the referring points in time of the early course of psychosis. The instrument is administered as a semi-structured interview with both the patient and a key informant. The obtained information is extended by a systematic examination of the clinician's case notes. Some results derived from an ongoing study on age and gender differences in onset and patterns of early course are added to demonstrate the use of the instrument.

Combined Modality Therapy↗

PubMed1992

[Estradiol inhibits dopamine mediated behavior in rats--an animal model of sex-specific differences in schizophrenia].

We found in a representative sample of 392 first hospital admissions for schizophrenia a higher mean age at onset in females by 3.2 to 3.9 years, whereas the lifetime risk was equal for both sexes. In males the rates of onset show a steep increase reaching the maximum value in the age group 15-24 years, followed then by a steady decrease. Females reach the first peak with a clear delay between 20 and 29 years. After the decrease a second smaller peak is observed consistently in females within the age group 45-49 years and over. After having excluded alternative explanations for this gender differences (for example, diagnosis artefacts, sociocultural factors), we hypothesized that the effect of oestradiol on the dopaminergic system enhances the vulnerability threshold for schizophrenia, which is lowered again during the menopause. Alternatively we assumed that testosterone reduces the vulnerability threshold and thus furthers the earlier onset of schizophrenia in males. We tested these hypotheses in animal models by investigating the effects of the gonadal hormones on haloperidol-induced catalepsy and on apomorphine-induced stereotypies in both neonatal and adult rats. Testosterone showed no clear influence on the tested dopamine-mediated behaviour. Oestradiol caused a significant reduction on both dopamine-agonist and dopamine-antagonist induced behaviour. These effects were stronger in neonatal animals. Since oestradiol caused a 2.8-fold reduction of dopamine receptor affinity for sulpiride, we assumed that the behavioural changes caused by oestradiol were accounted for by a down-regulation of the dopaminergic system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

[Are sex differences in schizophrenia stable on a transnational basis?].

The ABC-Schizophrenia-Study (Häfner et al. 1991), investigating a large, representative sample of 267 first admissions, did not find any gender differences in the lifetime morbidity risk for this disorder or in the frequency of nuclear symptoms in male and female schizophrenic patients. Marked gender differences, however, could be detected regarding the age at onset and its distribution and regarding illness behavior and certain secondary symptoms. The transnational stability of these findings was tested with data from the WHO studies "On Assessment and Reduction of Psychiatric Disability" (including 510 patients from 7 centres) and on "Determinants of Outcome of Severe Mental Disorders" (with 1,292 patients from 11 centres). Studying pooled data sets from the studies minimized centre-specific selection effects on sampling. Major results of the ABC-Schizophrenia-Study were validated: the lack of a gender difference in the morbidity risk (cumulative lifetime incidence rates) for schizophrenia; lower mean age at first admission in males; an early, marked peak in the distribution of the age at onset in males; a later and broader peak in this distribution in females with a second peak after age 40-45; equal frequency of nuclear symptoms in both sexes; gender differences in some specific contents of delusions, secondary affective symptoms, social adjustment and illness behavior.

Adult↗

PubMed1991

Oestradiol enhances the vulnerability threshold for schizophrenia in women by an early effect on dopaminergic neurotransmission. Evidence from an epidemiological study and from animal experiments.

In a representative sample of 392 first hospital admissions for schizophrenia from a population of 1.5 million we assessed the "true" age of onset by a semi-standardized interview "IRAOS". We demonstrated that the mean age at onset of the disease is 3-4 years higher in females than in males, with the lifetime risk being exactly equal. In males, the rates of onset show a steep increase - starting from school age and reaching their maximum value in the age group 15-24 years - followed by a steady decrease. Females reach the first peak with a clear delay between 20 and 29 years. After the decrease, a second smaller peak is observed consistently in females within the age group 45-49 years and over. After having excluded competing explanations, we hypothesized that the effect of oestradiol on the dopaminergic system enhances the vulnerability threshold, which is lowered again during the menopause. Alternatively, we assumed that testosterone reduces the vulnerability threshold and thus furthers the earlier onset of the disease in males. We tested the hypotheses in three animal models by examining the effect of gonadal hormones on haloperidol-induced catalepsy and on apomorphine-induced stereotypies in both neonatal and adult rats. No clear influence by testosterone was shown. Oestradiol caused a significant reduction of both dopamine-agonist and dopamine-antagonist induced behaviour. The effects were stronger in neonatal rats. Since oestradiol caused the dopamine (DA) receptor affinity for sulpiride to be reduced by a factor of 2.8, we assumed that the behavioural changes due to oestradiol were accounted for by a down-regulation of DA receptor sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗