Schizophrenia Bulletin Advance Access originally published online on February 16, 2005
Schizophrenia Bulletin 2005 31(3):769-780; doi:10.1093/schbul/sbi014
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Long-Term Course of Adolescent Schizophrenia
Consultant, Department of Child and Adolescent Psychiatry, Albert Ludwigs University, Freiburg, Germany
Professor of Child and Adolescent Psychiatry and Head, Department of Child and Adolescent Psychiatry, Albert Ludwigs University
Physician, Department of Child and Adolescent Psychiatry, Philipps University, Marburg, Germany
Professor of Child and Adolescent Psychiatry, Department of Child and Adolescent Psychiatry, Philipps University
Consultant, Department of Child and Adolescent Psychiatry, Albert Ludwigs University
Professor of Child and Adolescent Psychiatry and Head, Department of Child and Adolescent Psychiatry, Philipps University
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Abstract |
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Our study investigated premorbid functioning, course, and outcome in early-onset schizophrenia. All inpatients with DSM–III–R diagnoses of schizophrenia (n = 101) consecutively admitted between 1983 and 1988 to the Department of Child and Adolescent Psychiatry at the University of Marburg in Germany were included. To assess premorbid adaptation and precursor symptoms, we administered the Instrument for the Retrospective Assessment of the Onset of Schizophrenia, which we modified to assess children and adolescents. Symptomatology was measured by the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, and the Brief Psychiatric Rating Scale. In addition, the Global Assessment of Functioning was applied. Followup data for 81 patients (80.2%) were available. The mean duration of schizophrenia at followup was 9.5 ± 2.2 years. Assessment of the highest level of adaptive functioning revealed very good or good outcome in 19.8 percent of the patients, fair or poor outcome in 38.2 percent, and very poor outcome and gross impairment in 42.0 percent. Premorbid adjustment was the best predictor of outcome in our schizophrenia sample. A poor prognosis was found in patients with premorbid developmental delays and those who were introverted and withdrawn before their psychotic state.
Keywords: Early-onset schizophrenia / course / outcome / premorbid development
Several studies of adult schizophrenia patients have shown that disability following the disorder can be severe, even though the patients manage to stay out of the hospital (Johnstone et al. 1991; Beckmann et al. 1992; Harrison et al. 2001). In large-scale followup studies of adult schizophrenia patients, outcome was good in 25 percent of patients, about 50 percent achieved at least partial remission, and only 25 percent remained permanently hospitalized or grossly impaired (Ciompi and Müller 1976; Huber et al. 1979; an der Heiden et al. 1995; Mason et al. 1995; Harrison et al. 2001).
Analyzing studies on smaller samples, Weiner (1982) concluded that the outcome of schizophrenia beginning in adolescence is less favorable than that starting in adulthood. Only about 25 percent of the adolescent patients reached full recovery, 25 percent improved but suffered from continuing symptoms or occasional relapses, and the remaining 50 percent required continuing residential care. Although schizophrenia adolescents were not more likely to recover compared to adults, more of them (about 50%) remained grossly impaired.
Werry et al. (1991) followed up 30 children and adolescents with schizophrenia. They noted complete recovery in only 23 percent of their patients at followup. The authors concluded that schizophrenia in children and adolescents is a chronic or relapsing disorder accompanied by considerable disability and significant deterioration in adaptive function from already impaired premorbid levels (table 1 contains details).
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Gillberg et al. (1993) reassessed a population-based sample of 23 adolescents with schizophrenia. They described a good outcome in only 13 percent of their patients, 11 to 17 years after first diagnosis according to different kinds of register data. Only 8.7 percent of the patients showed an intermediate outcome.
In a more recent study, Lay et al. (2000) followed up 65 children and adolescents with schizophrenia more than 10 years after the first episode. Serious social disability was found in 66 percent of patients, and no or minimum dysfunction was found in 20 percent. In this study, a longer duration of inpatient stay was shown to be a prerequisite for a lower functioning at followup.
Schizophrenia psychoses in childhood are of considerable importance for child psychiatry but rare within the spectrum of schizophrenia. Eggers and Bunk (1997), who followed up 44 children with schizophrenia, noted the relatively high rates of complete and partial remission in the long-term course. They pointed out that none of the patients with chronic onset remitted completely. In patients with schizophrenia psychosis, Remschmidt et al. (1994) described a chronic course in 90.9 percent (10 of 11 patients) when beginning before age 14. On the other hand, Asarnow et al. (1994) observed a more favorable outcome in children with schizophrenia or schizoaffective psychosis with a substantial remission of symptoms of schizophrenia and a good social adjustment in 22 percent and a chronic course in 78 percent. In a more recent study, Remschmidt et al. (2000) followed up 38 patients with childhood-onset schizophrenia (age at onset: 5–14 years; followup time: 42 years). According to the Global Assessment Scale (GAS), Remschmidt et al. (2000) showed a fairly good outcome in only 16 percent of patients with childhood-onset schizophrenia, while a poor and moderate outcome was observed in 60 percent and 24 percent of patients, respectively.
In summary, most of the long-term followup studies in early-onset and very early onset schizophrenia patients demonstrate a worse outcome in adolescents compared to adults. Moreover, outcome in childhood-onset schizophrenia seems to be worse in comparison to that in adolescent-onset schizophrenia (Asarnow et al. 2001, 2004).
Therefore, the aim of our study was to investigate premorbid functioning, course, and outcome in a larger consecutive sample of early-onset schizophrenia. In addition, we attempted to identify predictors for outcome in adulthood at an early phase of illness, applying variables derived from previously published short-term studies (Remschmidt et al. 1991, 1994; Fleischhaker et al. 1998; Schulz 1998).
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Methods |
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Subjects
All inpatients with DSM–III–R (APA 1987) schizophrenia (n = 101) consecutively admitted between 1983 and 1988 to the Department of Child and Adolescent Psychiatry at the Philipps University in Marburg, Germany, were included in this followup study. From a total of 1,351 inpatients, 154 patients were selected with a suspected clinical diagnosis of schizophrenia. All of these patients with suspected early-onset schizophrenia were carefully reevaluated according to their symptomatology at first admission and were rediagnosed according to the ICD–10 (World Health Organization 1993) and DSM–III–R criteria of schizophrenia by a consensus rating of two experienced child psychiatrists. Out of the patients with suspected childhood- or adolescent-onset schizophrenia, a sample of 101 patients fulfilled DSM–III–R criteria of schizophrenia. The remaining 53 patients were withdrawn from the study because of substance-induced psychotic disorder (292.1) (n = 3), psychotic disorder due to general medical condition (293.8x) (n = 5), brief psychotic disorder (298.8) (n = 6), major depressive disorder (296.x) (n = 30), personality disorder (301.x) (n = 3), pervasive developmental disorder (299.8) (n = 3), or adjustment disorder (309.x) (n = 3).
The schizophrenia sample included in the followup study met the following criteria:
- They were less than 18 years old when they showed the first symptoms of schizophrenia.
- They were consecutively admitted to our department and received treatment as schizophrenia inpatients according to the DSM–III–R criteria.
Followup Assessment
Of the 101 patients (53 males, 48 females), 81 (80.2%) were assessed by a semistructured interview, either with the patient (n = 58) or with the relatives and/or medical staff (n = 23). For 6 other patients (5.9%) who had died by committing suicide, an interview with first or second degree relatives and/or the last treating physician was performed to complete the sets of medical records. Eleven (10.9%) patients refused a home visit. Three cases (3%) were not traceable. We found no significant differences in the characteristics at initial assessment between patients who were followed up and dropouts.
Instruments for Followup Evaluation
For the assessment of characteristics of the first episode, including sociodemographic data, premorbid adaptation, and precursor symptoms of schizophrenia, we administered the Instrument for the Retrospective Assessment of the Onset of Schizophrenia (IRAOS) (Häfner et al. 1990, 1992). This instrument was modified by our group for investigating children and adolescents and their relatives (Remschmidt et al. 1994; Tepper 1998). For this study, the IRAOS was administered by experienced clinicians who interviewed the patients or relatives directly. In addition, information was obtained from past medical records and a standardized documentation system.
To evaluate premorbid symptomatology, we developed a checklist of premorbid symptoms that could be classified as either "internalizing" or "externalizing." Examples of internalizing symptoms were mutism, mental slowness, social isolation, general anxieties, specific anxieties, and obsessive-compulsive symptoms. The externalizing dimension comprised items such as hyperactive and antisocial behavior, and aggression. A second part of the checklist was designed to include developmental retardation. Every kind of developmental retardation in the field of speech and language, motor development, reading, and writing was rated based on all the kinds of information we could gather on premorbid behavior through a careful analysis of the case histories, information from parents, and school reports. Each item of the checklist was evaluated as present or absent. For calculations, we classified three dimensions for the checklist as internalizing, externalizing, and developmental retardation. If one or more of the items of each dimension were present within a dimension, it was classified as being present.
The evaluation of premorbid symptomatology was performed independently by two investigators. If consensus was not achieved, a third senior researcher in child and adolescent psychiatry (E.S.) was consulted and a final best estimate was achieved.
Followup interviews were performed based on the IRAOS (Häfner et al. 1990, 1992) for the assessment of the age at onset, the characteristics of the first episode, and sociodemographic data. The age of the patients at onset of nonspecific psychopathological symptoms was defined as the age of the first occurrence of nonpsychotic symptoms. The age at onset of symptoms of schizophrenia was defined as the age of the first occurrence of symptoms of schizophrenia (according to the ICD–10).
The assessment of educational and occupational impairment was performed according to the IRAOS. Positive and negative symptoms of schizophrenia were evaluated using the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) developed by Andreasen (1982, 1984a, 1984b). The interrater reliability of both the SANS and the SAPS was found to be good, with 
values of 0.8 (Andreasen 1982; Moscarelli et al. 1987; Andreasen et al. 1991) with the exception of the SANS item "attention" ( value 0.67). As described elsewhere (Remschmidt et al. 1991), relating attentional impairment to negative symptoms seems to be problematic; therefore, we excluded this item from the rating scale. The summary scores of negative and positive symptoms were calculated according to Andreasen (1982). In addition to the evaluation of positive and negative symptoms, the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham 1962) was used to measure symptomatology and outcome during the followup investigation. The application of the BPRS in the followup studies of schizophrenia patients is well established (Thiemann et al. 1987; Bell et al. 1992; Deister and Marneros 1993). This scale has also proved to be effective for the evaluation of outcome in treatment studies of schizophrenia (Kane et al. 1988; Meltzer 1991; Beckmann et al. 1992). In our study, the BPRS total score and the BPRS depressive score (including items 1, 2, 5, and 9) were applied for statistical analysis.
To measure psychosocial adaptation, we used the Global Assessment of Functioning (GAF) scale (DSM–III; American Psychiatric Association 1980) and the Global Assessment Scale (GAS) (Endicott et al. 1976).
All interviews were conducted by experienced clinicians who had extensive experience with using the IRAOS, the SANS, the SAPS, the BPRS, the GAS, and the GAF in prior studies (Remschmidt et al. 1991; Schulz 1998). The full package of instruments was introduced at two training seminars for principal investigators. During this training, standard videotapes and case vignettes were used. Each principal investigator had to rate three standard videotapes. A deviation from the standard rating of one point was allowed for each item and for the summary scores. Before starting the followup interviews, the principal investigators were trained by holding live interviews with an observer present. The observer made independent ratings.
For the evaluation, we compared the values at followup with the values for the same patient at initial assessment.
Statistical Methods
A comparison was drawn between patients we followed up and dropouts, as well as between genders, using chi-square tests for categorical variables, if expected cell frequencies could be regarded as large enough. Otherwise, Fisher's exact test was applied. For continuous variables, median test or t test was used. The significance level was fixed at alpha = 0.05. All statistical calculations were performed with SAS statistical analysis programs (SAS Institute 1989).
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Results |
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Sample Characteristics
After a mean duration of schizophrenia of 9.5 years (±2.2 years; range 4–14 years), 81 patients (80.2%) of the schizophrenia sample were investigated.
The first nonpsychotic symptoms occurred on average at age 14.5 years, followed by the first symptoms of schizophrenia approximately 1.5 years later. The age at first admission because of schizophrenia was 16.5 years (±2.1 years; range 11–18 years) (table 2).
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According to the characteristics of the onset of schizophrenia (first presentation, first symptoms of schizophrenia, first hospitalization for schizophrenia, and age at followup), we found no significant differences between males and females (table 3).
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In table 4, the diagnoses according to DSM–III–R criteria and the course of illness according to ICD–10 criteria at followup are presented. There are no significant differences between males and females, but there was a trend toward a more serious course in males. We observed an episodic course of schizophrenia with relapses and readmissions in 40 percent (n = 32) of patients, with a mean number of 2.9 readmissions.
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Family History
Patients with a family history of schizophrenia or schizoaffective disorder (n = 22) as opposed to those without (n = 56) had a significantly lower GAF score (table 5) and higher scores of both positive and negative symptoms (SAPS: mean 8.0 vs. 5.5; median test p = 0.08; SANS: mean 4.2 vs. 3.4; median test p = 0.32). A family history of affective disorder did not increase the risk of poor outcome in this sample of schizophrenia patients.
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Premorbid Characteristics
Figure 1 demonstrates premorbid symptoms of internalizing, externalizing, and developmental retardation in the schizophrenia sample. In only 19 patients (19.6%) did we find no impairment. Premorbid symptoms of internalizing were present in 63 patients (63.6%) and premorbid symptoms of externalizing in 29 patients (29.3%).
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There were no differences with regard to psychosocial adjustment (measured by the GAF) between those individuals with premorbid internalizing (n = 63) or externalizing (n = 29) symptoms.
However, there was a significant difference between the patients who had premorbid developmental retardation and those who did not in regard to a lower level of psychosocial adjustment, measured by the GAF (median test: p = 0.0007) (table 5).
Characteristics of the Onset of Schizophrenia and Followup
Social adjustment in terms of the GAF was favorably influenced by the following four factors:
- An acute course at onset of the first episode of schizophrenia (beginning of acute symptoms in <1 month).
- A shorter duration of first episode (duration of first episode <6 months).
- An older age at onset of schizophrenia (age of onset >14 years).
- Female sex (table 5).
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Psychopathology at Followup |
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Depressive symptoms
Figure 2 shows depressive symptoms at followup according to the BPRS. The figure demonstrates very clearly that a substantial number of these patients (39.7%; n = 23) revealed severe or moderate symptoms of depression.
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Negative and positive symptoms
The same applies to negative symptoms as compared to positive ones. Nineteen of these patients (32.8%) had severe negative symptoms, 20 patients (34.9%) mild negative symptoms, and 19 patients minimal negative symptoms. In contrast, severe positive symptoms were found in only 10.3 percent of the patients, whereas most schizophrenia patients showed only moderate (41.4%) or minimal (48.3%) symptoms on the SAPS. The severity of positive and negative symptoms was defined in the following way: scores between 0 and 4 were rated as minimal, scores between 4 and 8 as moderate, and scores between 8 and 20 as severe.
Global Outcome
A subdivision into three categories was introduced for the GAS. The rating "poor outcome" (GAS score 
40) was given if the first four items (needs constant supervision, needs some supervision, unable to function in almost all areas, major impairment in several areas) were present, a "moderate outcome" rating was given if the items ranging from 41 to 70 (any serious symptomatology, moderate symptoms, some mild symptoms) were present, and a "good outcome" rating was given if the items ranging from 71 to 100 (minimal symptoms, transient symptoms, good functioning, no symptoms) were present.
The result of this rating is demonstrated in table 6, which also compares our child and adolescent-onset schizophrenia sample (n = 81) with a sample of childhood-onset schizophrenia (n = 38, age at onset 12.7, age at followup 55) from the Department of Child and Adolescent Psychiatry in Marburg (Remschmidt et al. 2000). The patients of the very early onset sample had been treated as inpatients between 1920 and 1960. Although the samples differed in age at onset and followup period, a tendency toward a worse outcome of the very early onset group was found.
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Educational Outcome
Prior to the onset of schizophrenia, all patients attended school. The public school system in Germany is divided into three branches following four years of elementary school education: Hauptschule continues up to grade 9, Realschule up to grade 10, and Gymnasium up to grade 13.
In table 7, school graduation at followup is shown. The rate of achievement of different graduations among Germans between the ages of 25 and 30 is compared (Zentrum für Umfragen, Methoden und Analysen 1995).
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With regard to school education, 28 patients (29.5%) had not graduated (3% of the general population), 57 patients (60.0%) graduated from either grade 9 or 10 within different settings (69% of the general population), and only 10 (10.5%) graduated from secondary school, which is composed of 12/13 years of school attendance (28% of the general population). There was no significant difference between male and female patients with respect to school education at followup (chi-square: nonsignificant).
Living Situation/Family Status at Followup
Only 15 patients (17%) needed hospitalization at followup, 28 patients (31.8%) used semisheltered/sheltered living, and 45 patients (51.1%) lived in normal housing (table 8).
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Regarding the occupational status at the time of the interview, only 25 patients (28.7%) were employed on a nonsheltered basis, 13 patients (14.9%) were employed in a semisheltered labor market, and 33 patients (37.9%) were employed in a clinical setting; 16 patients (18.4%) did not work. The living conditions and occupational status were similar for males and females, with no significant difference (table 8; chi-square: nonsignificant).
Seventy-five of the patients (84.2%) were single at followup or at the time of death, only 5 (5.7%) were married, and 8 patients (9.1%) lived in a relationship. Remarkably, more male patients lived alone than female (table 9; chi-square: nonsignificant).
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Level of Social Adjustment at Followup
In table 10, the GAF results are shown. Assessment of the highest level of adaptive functioning revealed outcome as follows: very good and good (19.8%), fair and poor (38.3%), and very poor and grossly impaired (42%). More male than female patients showed a very poor and grossly impaired social adjustment at followup (table 10; chi-square p = 0.06).
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Discussion |
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This study was designed to provide information on the characteristics, course, and outcome of adolescent schizophrenia.
Limitations
A possible methodological limitation relates to the clinical sample and the study design. Because of the presence of a specialized rehabilitation center for early-onset schizophrenia in our area, results may be biased. However, we did not find differences between patients admitted from home and patients admitted from the rehabilitation center.
Eighty-one of 101 patients were assessed in a semistructured interview with the patient, relatives, or medical staff. Data were incomplete in 20 patients, so these patients were not included in the analysis. However, participants and nonparticipants did not differ in regard to the diagnosis, sociodemographic data, and inpatient course of illness. Therefore, we think that our sample is representative.
A further limitation could be said to be that only cross-sectional followup data were given on the outcome statistics of symptomatology and social functioning. As a result, the values reported for positive symptoms were low and those for negative symptoms were fairly high, because negative symptoms represent a fairly stable dimension and positive symptoms a dimension subject to fluctuation because of its episodic nature.
Strengths
Because of the low incidence of childhood- and adolescent-onset schizophrenia, most of the previous studies in the field included relatively few patients (table 1). To our knowledge, the present study—with 101 consecutively admitted patients and a mean followup of 9.5 years—is the biggest sample of early-onset schizophrenia to date.
Schizophrenia psychosis with early manifestation has a poor prognosis. As demonstrated, course and outcome are influenced by the patient's premorbid personality. With a very good or good outcome in 20 percent of patients, our study compares well to previous reports by Lay et al. (2000), Werry et al. (1991), and Krausz and Müller-Thomsen (1993), which reported 20 to 23 percent (table 1).
Adult long-term investigations have generally found that patients have better outcomes; for example, in the long-term study in Bonn, 56 percent of patients with the diagnosis of schizophrenia were found to have recovered and to be fully employed (Huber et al. 1979). Similar recovery rates were reported in other adult long-term studies (an der Heiden et al. 1995; Mason et al. 1995; Harrison et al. 2001). This supports the view of a less severe course of illness in later-onset schizophrenia. The better outcome may, in part, reflect a less severe course of illness in these patients that is at least partly caused by already established social roles (e.g., school graduate, member of a stable partnership, person living independently).
The general outcome found in this study was poor but is still better than in the very early onset study of Asarnow et al. (1994), who used the same measure (GAS) that we used. Twenty percent of our patients, compared with 22 percent in Asarnow's study, had a good outcome; and 42 percent of our patients, compared with 60 percent of Asarnow's, had a poor outcome. The results in the very early onset study of Asarnow are similar to our results with a very early onset schizophrenia study sample. Part of our very early onset sample (Remschmidt et al. 2000) was investigated recently by Eggers and Bunk (1997), who found a somewhat better outcome. The better outcome in adolescent-onset schizophrenia may, in part, reflect a less severe course of illness in patients who fall ill during adolescence.
Six patients could not be interviewed because they were deceased, having committed suicide. This mortality rate is far higher than in a comparable age group of the general population, where a mortality rate of 1.97/1,000 was found in 10- to 30-year olds (Statistisches Bundesamt 1998).
Patients with premorbid developmental delays and patients who are internalizing and withdrawn before the beginning of their psychotic state are at risk of a poor outcome. More attention to premorbid features is essential in the development of preventive measures.
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Footnotes |
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Send reprint requests to Dr. Christian Fleischhaker, Department of Child and Adolescent Psychiatry, Albert Ludwigs University Freiburg, Hauptstr. 8, D–79104 Freiburg, Germany; e-mail: fleischhaker{at}psyallg.ukl.uni-freiburg.de.
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References |
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-
American Psychiatric Association. DSM–III: Diagnostic and Statistical Manual of Mental Disorders 3rd ed. Washington, DC: APA 1980.
American Psychiatric Association. DSM–III–R: Diagnostic and Statistical Manual of Mental Disorders 3rd ed. Washington, DC: APA 1987 revised.
an der Heiden, W, Krumm, B, Mueller, S, Weber, I, Biehl, H, Schaefer, M. Mannheimer Langzeitstudie der Schizophrenie. Nervenarzt 1995; 66:820–827.[Medline]
Andreasen, NC. Negative symptoms in schizophrenia: Definition and reliability. Archives of General Psychiatry 1982; 39:784–788.[Abstract]
Andreasen, NC. The Scale for the Assessment of Negative Symptoms (SANS) Iowa City, IA: University of Iowa 1984a.
Andreasen, NC. The Scale for the Assessment of Positive Symptoms (SAPS) Iowa City, IA: University of Iowa 1984b.
Andreasen, NC, Flaum, M, Arndt, S, Alliger, R, Swayze, VW. Positive and negative symptoms: Assessment and validity. In Marneros, A, Andreasen, NC, Tsuang, MT (Eds.). Negative Versus Positive Schizophrenia Berlin, Germany: Springer Verlag 1991 pp. 28–51.
Asarnow, JR, Tompson, MC, Goldstein, MJ. Childhood-onset schizophrenia: A follow-up study. Schizophrenia Bulletin 1994; 20:599–617.
Asarnow, JR, Tompson, MC, Goldstein, MJ. Psychosocial factors: The social context of child and adolescent-onset schizophrenia. In Remschmidt, H (Ed.). Schizophrenia in Children and Adolescents Cambridge, U.K.: Cambridge University Press 2001.
Asarnow, JR, Tompson, MC, McGrath, EP. Annotation: Childhood-onset schizophrenia: Clinical and treatment issues. Journal of Child Psychology and Psychiatry, and Allied Disciplines 2004; 45:180–194.
Beckmann, H, Fritze, J, Franzek, E. The influence of neuroleptics on specific syndromes and symptoms in schizophrenics with unfavourable long-term course: A 5-year follow-up study of 50 chronic schizophrenics. Neuropsychobiology 1992; 26:50–58.[Medline]
Bell, M, Milstein, R, Beam-Goulet, J, Lysaker, P, Cicchetti, D. The Positive and Negative Syndrome Scale and the Brief Psychiatric Rating Scale: Reliability, comparability, and predictive validity. Journal of Nervous and Mental Disease 1992; 180:723–728.[Medline]
Ciompi, L and Müller, C. Lebensweg und Alter der Schizophrenen. Eine katamnestische Langzeitstudie bis ins Senium Berlin, Germany: Springer 1976.
Deister, A and Marneros, A. Long-term stability of subtypes in schizophrenic disorders: A comparison of four diagnostic systems. European Archives of Psychiatry and Neurological Sciences 1993; 242:184–190.
Eggers, C and Bunk, D. The long-term course of childhood-onset schizophrenia: A 42-year followup. Schizophrenia Bulletin 1997; 23:105–117.
Endicott, J, Spitzer, RL, Fleiss, JL, Cohen, J. The Global Assessment Scale: A procedure for measuring overall severity of psychiatric disturbance. Archives of General Psychiatry 1976; 33:766–771.[Abstract]
Fleischhaker, C, Schulz, E, Remschmidt, H. Depressive symptoms and plasma monoamine levels as predictors of response to clozapine treatment in adolescents with schizophrenia. Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie 1998; 26:235–243.
Gillberg, C, Hellgren, L, Gillberg, C. Psychotic disorders diagnosed in adolescence. Outcome at age 30 years. Journal of Child Psychology and Psychiatry, and Allied Disciplines 1993; 34:1173–1185.
Häfner, H, Riecher, A, Maurer, K, Meissner, S, Schmidtke, A, Fätkenheuer, B, Löffler, W, an der Heiden, W. Instrument for the retrospective assessment of the onset of schizophrenia (IRAOS). Zeitschrift für klinische Psychologie und Psychotherapie 1990; 19:230–255.
Häfner, H, Riecher-Rössler, A, Hambrecht, M, Maurer, K, Meissner, S, Schmidtke, A, Fätkenheuer, B, Löffler, W, van der Heiden, W. IRAOS: An instrument for the assessment and early course of schizophrenia. Schizophrenia Research 1992; 6:209–223.[CrossRef][ISI][Medline]
Harrison, G, Hopper, K, Craig, T, Lask, E, Siegel, C, Wanderling, J, Dube, KC, Ganev, K, Giel, R, an der Heiden, W, Holmberg, SK, Janca, A, Lee, PWH, Leon, CA, Malhorta, S, Marsella, AJ, Nakane, Y, Sartorius, N, Shen, Y, Skoda, C, Thara, R, Tsirin, SJ, Varma, VK, Walsh, D, Wiersma, D. Recovery from psychotic illness: A 15- and 25-year international follow-up study. British Journal of Psychiatry 2001; 178:506–517.
Huber, G, Gross, G, Schüttler, R. Schizophrenie. Eine verlaufs- und sozialpsychiatrische Langzeitstudie Berlin, Germany: Springer 1979.
Inoue, K, Nakajima, T, Kato, N. A longitudinal study of schizophrenia in adolescence: I. The one- to three- year outcome. Japanese Journal of Psychiatry and Neurology 1986; 40:143–151.
Jarbin, H, Ott, Y, von Knorring, A-L. Adult outcome of social function in adolescent-onset schizophrenia and affective psychosis. Journal of the American Academy of Child and Adolescent Psychiatry 2003; 42:176–183.[CrossRef][Medline]
Kane, J, Honigfeld, G, Singer, J, Meltzer, H. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Archives of General Psychiatry 1988; 45:789–796.[Abstract]
Kimura, S, Asai, S, Wakeno, M, Aoki, N. On early and mid-onset schizophrenia, Part 1: Phenomenological aspects. Folia Psychiatrica et Neurologica Japonica 1978; 32:41–56.[Medline]
Krausz, M. Schizophrenia in adolescents—A follow-up study. Psychiatrische Praxis 1990; 17:107–114.[Medline]
Krausz, M and Müller-Thomsen, T. Schizophrenia with onset in adolescence: An 11-year followup. Schizophrenia Bulletin 1993; 19:831–841.
Lay, B, Blanz, B, Hartmann, M, Schmidt, MH. The psychosocial outcome of adolescent-onset schizophrenia: A 12-year followup. Schizophrenia Bulletin 2000; 26:801–816.
Johnstone, EC, Frith, CD, Leary, J, Owens, DG, Wilkins, S, Hershon, HI. Background, method and general description of the sample. British Journal of Psychiatry 1991; 159:7–12.
Mason, P, Harrison, G, Glazebrook, C, Medeley, I, Dalkin, T, Croudace, T. Characteristics of outcome in schizophrenia at 13 years. British Journal of Psychiatry 1995; 167:596–603.
Meltzer, HY. The effect of clozapine and other atypical antipsychotic drugs on negative symptoms. In Marneros, A, Andreasen, NC, Tsuang, MT (Eds.). Negative Versus Positive Schizophrenia Berlin, Germany: Springer Verlag 1991.
Moscarelli, M, Maffei, C, Cesana, BM, Boato, P. An international perspective on assessment of negative and positive symptoms in schizophrenia. American Journal of Psychiatry 1987; 144:1595–1598.
Overall, JE and Gorham, DR. The Brief Psychiatric Rating Scale. Psychological Reports 1962; 10:799–812.[ISI]
Remschmidt, H., Martin, M., Fleischhaker, C., Hennighausen, K., Gutenbrunner, C., Schulz, E. A forty-two year follow-up study of childhood-onset schizophrenia. Implications for the Kraepelian dichotomy, Unpublished manuscript, 2000.
Remschmidt, H, Martin, M, Schulz, E, Gutenbrunner, C, Fleischhaker, C. The concept of positive and negative schizophrenia in child and adolescent psychiatry. In Marneros, A, Andreasen, NC, Tsuang, MT (Eds.). Negative Versus Positive Schizophrenia Berlin, Germany: Springer 1991 pp. 219–242.
Remschmidt, HE, Schulz, E, Martin, M, Warnke, A, Trott, GE. Childhood-onset schizophrenia: History of the concept and recent studies. Schizophrenia Bulletin 1994; 20:727–745.
SAS Institute. SAS/STAT User's Guide, Version 6 Cary, NC: SAS Institute 1989.
Schmidt, MH and Blanz, B. Behandlungsverlauf und Katamnesen bei 122 Psychosen in der Adoleszenz. [Course and follow up investigation in 122 psychotic adolescents]. In Nissen, G (Ed.). Endogene Psychosyndrome Göttingen, Germany: Verlag Hans Huber 1992 pp. 163–177.
Schulz, E. Verlaufsprädiktoren schizophrener Psychosen in der Adoleszenz. Entwicklungspsychopathologische, neurochemische und psychopharmakologische Befunde Göttingen, Germany: Hogrefe 1998.
Statistisches Bundesamt. Statistical Yearbook 1998 for the Federal Republic of Germany Stuttgart, Germany: Metzler-Pöschel 1998.
Tepper, K. Katamnese einer vollständigen Inanspruchnahmepopulation (1983–1988) schizophren erkrankter Kinder und Jugendlicher Marburg, Germany: Görich and Weiershäuser 1998.
Thiemann, S, Csernansky, JG, Berger, PA. Rating scales in research. The case of negative symptoms. Psychiatry Research 1987; 20:47–55.[CrossRef][ISI][Medline]
Weiner, JS. Child and Adolescent Psychopathology New York, NY: Wiley 1982.
Werry, JS, McClellan, JM, Chard, L. Childhood and adolescent schizophrenic, bipolar and schizoaffective disorders: A clinical and outcome study. Journal of the American Academy of Child and Adolescent Psychiatry 1991; 30:457–465.[ISI][Medline]
World Health Organization. In Dilling, H, Mombour, W, Schmidt, MH (Eds.). ICD-10: Internationale Klassifikation psychischer Störungen Göttingen, Germany: Huber 1993.
Zentrum für, Umfragen and Methoden und, Analysen. Demographic Data: Anonymized Sample of the German Microcensus 1995 (ZUMA-file) Mannheim, Germany: ZUMA 1995.
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