Kurt Maurer

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

Häfner H, Löffler W, Maurer K, Hambrecht M, an der Heiden W. Depression, negative symptoms, social stagnation and social decline in the early course of schizophrenia.

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.

The ABC schizophrenia study: a preliminary overview of the results

Abstract 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.

Schizophrenia and depression: Challenging the paradigm of two separate diseases—A controlled study of schizophrenia, depression and healthy controls☆

BACKGROUND We studied descriptive and causal associations between schizophrenia, depressive symptoms and episodes of depression. METHODS Untreated psychotic, depressive and negative symptoms were assessed retrospectively from onset until first admission using the IRAOS in a population-based sample of 232 first episodes of schizophrenia. A representative subsample of 130 patients, studied retrospectively until onset and followed up prospectively over 6 months after first admission, were compared with 130 age- and sex-matched healthy population controls and with 130 equally matched first admissions for unipolar depressive episodes. RESULTS The lifetime prevalence of depressive mood (>or=2 weeks) at first admission for schizophrenia was 83%. The most frequent initial symptom of schizophrenia was depressive mood, appearing more than 4 years before first admission and followed by negative symptoms and functional impairment. Showing considerable overlap in symptoms and functional impairment at their initial stages, schizophrenia and unipolar depression became clearly distinguishable with the emergence of psychotic symptoms. In the first psychotic episode 71% presented clinically relevant depressive symptoms, 23% fulfilled the ICD-10 criteria for a depressive episode. With remitting psychosis the prevalence of depression, too, decreased. The high frequency of depressive symptoms at the prepsychotic prodromal stage and their increase and decrease with the psychotic episode suggests that depression in schizophrenia might be expression of an early, mild stage of the same neurobiological process that causes psychosis. CONCLUSIONS The high prevalence of depression in the population and the diversity of its causes prompted us to speculate about a hierarchical model of preformed dimensional patterns of psychopathology.

Early detection and secondary prevention of psychosis: facts and visions.

Abstract.As effective and practical approaches to primary and universal prevention of psychosis are lacking, intervention efforts are targeted at the early stages of schizophrenia to prevent (by way of secondary prevention) or postpone psychosis onset, reduce severity of illness or at least ameliorate the social consequences involved. Early intervention requires early detection and early recognition (diagnosis) of persons at risk and early prediction of psychosis. Within the German Research Network on Schizophrenia (GRNS) awareness programmes are being carried out in several German cities, and these efforts are already improving utilisation of early-recognition and early-prediction services by at risk persons. The empirical basis of developing a two-step early-recognition inventory and strategies of application will be discussed. This instrument is supplemented by a set of cognitive tests, prospectively validated in the GRNS. Results from preliminary analysis of data covering a two-year period demonstrate that the inventory and the cognitive tests are readily accepted. When used for screening in non-specialist settings and at the next level, i. e. at early-recognition centres, they seem to permit identification of at-risk persons. Early intervention is being tested 1) in a randomised controlled multi-centre trial consisting of a specially developed cognitive-behavioural therapy in the early (prepsychotic) prodromal state and 2) on additional treatment with appropriate doses of amisulpride in the late prodromal (early psychotic) state. Preliminary data from Study 1 covering 16.3 months show significantly fewer transitions to psychosis and from Study 2 reduced positive and negative symptoms and improved global functioning compared with controls who had received normal clinical treatment. As a result, both the early-recognition inventory plus cognitive tests and the two therapy strategies are feasible. We hope that the favourable trend indicated by the preliminary data will be confirmed in the final analysis planned for 2005 and the objective of implementing effective and practical secondary prevention of psychosis and its consequences will be attained.

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 suprisingly 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.

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 determing social outcome appeared to the 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.

Preventing progression to first-episode psychosis in early initial prodromal states.

BACKGROUND Young people with self-experienced cognitive thought and perception deficits (basic symptoms) may present with an early initial prodromal state (EIPS) of psychosis in which most of the disability and neurobiological deficits of schizophrenia have not yet occurred. AIMS To investigate the effects of an integrated psychological intervention (IPI), combining individual cognitive-behavioural therapy, group skills training, cognitive remediation and multifamily psychoeducation, on the prevention of psychosis in the EIPS. METHOD A randomised controlled, multicentre, parallel group trial of 12 months of IPI v. supportive counselling (trial registration number: NCT00204087). Primary outcome was progression to psychosis at 12- and 24-month follow-up. RESULTS A total of 128 help-seeking out-patients in an EIPS were randomised. Integrated psychological intervention was superior to supportive counselling in preventing progression to psychosis at 12-month follow-up (3.2% v. 16.9%; P = 0.008) and at 24-month follow-up (6.3% v. 20.0%; P = 0.019). CONCLUSIONS Integrated psychological intervention appears effective in delaying the onset of psychosis over a 24-month time period in people in an EIPS.

Acute effects of treatment for prodromal symptoms for people putatively in a late initial prodromal state of psychosis

BACKGROUND People in a putatively late prodromal state not only have an enhanced risk for psychosis but already suffer from mental and functional disturbances. AIMS To evaluate the acute effects of a combined supportive and antipsychotic treatment on prodromal symptoms. METHOD Putatively prodromal individuals were randomly assigned to a needs-focused intervention without (n=59) or with amisulpride (n=65). Outcome measures at 12-weeks effects were prodromal symptoms, global functioning and extrapyramidal side-effects. RESULTS Amisulpride plus the needs-focused intervention produced superior effects on attenuated and full-blown psychotic symptoms, basic, depressive and negative symptoms, and global functioning. Main side-effects were prolactin associated. CONCLUSIONS Coadministration of amisulpride yielded a marked symptomatic benefit. Effects require confirmation by a placebo-controlled study.

Onset and Early Course of Schizophrenia

When, with what symptoms and how schizophrenia really begins, and how this beginning can be distinguished from already existing deficits or antecedents are all interesting questions. They arise following the papers of Crow et al. and Walker et al. on the antecedents of psychosis. Kraepelin (1909) and Bleuler (1911) had already observed that the disease rarely begins without non-specific symptoms in advance. Kraepelin (1909) mentioned, for instance, “small changes in emotional life, irritability, loss of interest, overactivity and poor concentration.” DeLisi et al. (1986) and Huber and Gross (1989) recently expressed the expectation that the elucidation of the prodromal phase might provide a new understanding of the psychopathology and etiology of schizophrenia.