Negative symptoms and their association with depressive symptoms in the long-term course of schizophrenia.

Depressive symptoms abound in schizophrenia and even in subclinical states of the disorder. We studied the frequency of these symptoms and their relationship to negative symptoms from the first psychotic episode on over a long-term course of 134 months on data for 107 patients in our ABC Schizophrenia Study. Prevalence rates of 90 % for presenting at least one negative symptom and of 60 % for presenting at least one depressive symptom in the first psychotic episode illustrate the frequency of these syndromes. After the remission of psychosis the rates fell to 50 % (negative symptoms) and 40 % (depressive symptoms) over a period of 5 years, remaining stable thereafter. After we broke the negative syndrome down into (SANS) subsyndromes, a positive association emerged between anhedonia and depressive symptoms and remained stable over the entire period studied. In contrast, the association between abulia and depression grew increasingly pronounced over the illness course. However, a more detailed look revealed this to be the case in female patients only, whereas male patients showed no such association of these symptom dimensions. We have no explanation at hand for this sex difference yet.

Smaller than expected cognitive deficits in schizophrenia patients from the population-representative ABC catchment cohort.

Most neuropsychological studies on schizophrenia suffer from sample selection bias, with male and chronic patients being overrepresented. This probably leads to an overestimation of cognitive impairments. The present study aimed to provide a less biased estimate of cognitive functions in schizophrenia using a population-representative catchment area sample. Schizophrenia patients (N = 89) from the prospective Mannheim ABC cohort were assessed 14 years after disease onset and first diagnosis, using a comprehensive neuropsychological test battery. A healthy control group (N = 90) was carefully matched according to age, gender, and geographic region (city, rural surrounds). The present sample was representative for the initial ABC cohort. In the comprehensive neuropsychological assessment, the schizophrenia patients were only moderately impaired as compared to the healthy control group (d = 0.56 for a general cognitive index, d = 0.42 for verbal memory, d = 0.61 for executive functions, d = 0.69 for attention). Only 33 % of the schizophrenia patients scored one standard deviation unit below the healthy control group in the general cognitive index. Neuropsychological performance did not correlate with measures of the clinical course including age at onset, number of hospital admissions, and time in paid work. Thus, in this population-representative sample of schizophrenia patients, neuropsychological deficits were less pronounced than expected from meta-analyses. In agreement with other epidemiological studies, this suggests a less devastating picture of cognition in schizophrenia.

Investigating the long-term course of schizophrenia by sequence analysis.

In the present study we set out to explore the long-term clinical course of schizophrenia in a holistic manner by adopting sequence analysis. Our aim was to identify course types of illness by means of cluster analysis. The study was based on course and outcome data for 107 patients followed up over 134 months after first admission in the ABC Schizophrenia Study. Focusing on the main syndromes (positive, negative, depressive and unspecific symptoms) and their combinations we looked for similarities in individual illness courses using the 'optimal matching' method. A cluster analysis performed on the resulting similarity matrix yielded two main groups (a 'improving' and a 'chronic' group), which comprised a total of six different types of illness course. The course types differed in both quantitative (frequency of syndromes and syndrome combinations) and qualitative terms (clinical presentation, sequence of syndromes). Cluster membership was only rarely, but clearly associated with sociodemographic characteristics, treatment data and other illness variables.

Prodromal unfolding: the validation of the Schizotypic Syndrome Questionnaire model in a sample of first-episode schizophrenic patients.

AIM: Validation of Van Kampen's Schizotypic Syndrome Questionnaire (SSQ) model of schizophrenic prodromal unfolding. The SSQ model comprises 12 negative, asocial and psychotic-like symptoms that are hypothesized to determine each other in terms of cause and effect. METHOD: Use was made of the Interview for the Retrospective Assessment of the Onset of Schizophrenia (IRAOS)-dependent retrospective data assembled in the Mannheim Age-Beginning-Course Study sample of first-episode schizophrenic patients to measure the SSQ symptoms. Both the mean positions of the IRAOS-assessed symptoms on a continuum representing the proportion of total time of pre-psychotic disturbance and the outcome of a series of LISREL analyses conducted on the IRAOS-dependent data were addressed. RESULTS: Both kinds of data supported the validity of the SSQ model; however, this was after introducing some (relatively minor or demonstrable ineffective) changes in the model as the 'translation' of the SSQ symptoms by means of the IRAOS was not always easy, or proved even impossible in the case of one symptom. CONCLUSIONS: The conclusion seems warranted that the present investigation supports the validity of the SSQ model as a model of pre-psychotic and prodromal unfolding in patients diagnosed as suffering from schizophrenia. From a theoretical perspective, arguments are presented to interpret the SSQ model as a model of the core or principal symptoms of schizophrenia, including their temporal unfolding.

Evidence for separate diseases?: Stages of one disease or different combinations of symptom dimensions?

OBJECTIVE: We tested Kraepelin's dichotomy model by studying the separability of schizophrenia and depression on the basis of symptoms and illness course. MATERIALS AND METHODS: Matched untreated patients with schizophrenia and depression (n = 130 each) and 130 "healthy" controls were assessed from onset to first admission. In a second study the same variables were studied in 107 patients with schizophrenia over a homogenised follow-up of 134 months (11.2 years). RESULTS: The symptom most frequently marking the onset of both schizophrenia and depression was depressive mood. Both disorders exhibited the same prodromal core syndrome. It was not until the emergence of positive symptoms that the disorders became separable by the international classification systems. Depression remained the most frequent syndrome over the entire course of schizophrenia. CONCLUSION: Depression does not represent comorbidity, but an integral part of psychosis. A dimensional disease model based on successively emerging hierarchical symptom patterns, not unknown to the later Kraepelin, is offered as an explanation.

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.

Depression in the long-term course of schizophrenia.

Depressive symptoms are quantitatively and qualitatively among the most important characteristics of schizophrenia. The following contribution reports on the prevalence of depression in 107 patients of the ABC schizophrenia study over 12 years after first hospital admission, looks into a preponderance of depression at certain stages of the illness and the predictive value of depressive symptoms for course and outcome. All but one of the 107 patients experienced one to 10 episodes of depressed mood between index assessment and long-term follow-up. In any month of the observation period about 30-35% of the patients presented at least one symptom of the depressive core syndrome (depressive mood, loss of pleasure, loss of interests, loss of self-confidence, feelings of guilt, suicidal thoughts/suicide attempt). Depressive symptoms are particularly frequent during a psychotic episode at a rate of approximately 50%. There were moderate but statistically significant correlations between the amount of depressive symptoms during a psychotic episode and the frequency of relapses, defined by hospital admissions as well as the total length of inpatient treatment. Depression occurring in the interval was not associated with an increased need for inpatient treatment.

The early course of schizophrenia and depression*.

OBJECTIVE: Risk factors, emergence and accumulation of symptoms in the untreated early course were studied as a basis for understanding the relationship between schizophrenia and depression. MATERIALS AND METHODS: 130 representative first admissions for schizophrenia were compared retrospectively with 130 individually matched first admissions for depressive episodes and with 130 healthy controls. RESULTS: Onsets of schizophrenia and severe depression were marked by depressive symptoms, followed by negative symptoms and functional impairment. This prodromal core syndrome became more prevalent as the disorders progressed, and it reappeared in psychotic relapses. Psychotic symptoms emerged late, indicating a different and more severe "disease pattern". CONCLUSION: The prevalence of depressive symptoms in the general population and at the prodromal stage of numerous mental disorders precipitated by various psychological and biological factors suggests that depression might be an expression of an inborn mild reaction pattern of the human brain. With progressing brain dysfunction more severe patterns like psychosis are expressed.

Modeling the early course of schizophrenia.

Using the Interview for the Retrospective Assessment of the Onset of Schizophrenia (IRAOS), we assessed 170 first illness episodes with a nonpsychotic prodromal stage (73% of the population-based Age, Beginning, Course [ABC] study sample of 232 first illness episodes of schizophrenia from a German population of about 1.5 million). Conrad's (1958) and Docherty et al.'s (1978) stage models of the early course presume unidirectional and compelling patterns of symptom manifestation. Using structural equation modeling, we tested the explanatory power of the stages as latent variables and to what extent these models tally with each other and with data on symptom onset. The models neither converged nor were they confirmed. The reasons for and possible implications of this result will be discussed. We also tested, using various techniques, a causal model of the determinants of social course. The only significant predictors of 5-year social outcome turned out to be social development at psychosis onset and the socially adverse illness behavior of young men. The influence of the traditional predictors, age and gender, type of onset (chronic, acute), and symptomatology, was mediated by these two variables assessed at the end of the prodromal stage.

Precipitation and determination of the onset and course of schizophrenia by substance abuse--a retrospective and prospective study of 232 population-based first illness episodes.

Onset and lifetime prevalence of substance abuse were assessed retrospectively using the IRAOS interview in a population-based, controlled sample of 232 first episodes of schizophrenia (ABC sample). Subjects with schizophrenia were twice as likely as controls to have a lifetime history of substance abuse at the age of first admission (alcohol abuse: 23.7 versus 12.3%; drug abuse: 14.2 versus 7.0%). 88% of the patients with drug abuse took cannabis. The sequence of substance abuse and schizophrenia was studied on the timing of abuse onset and illness onset, the latter as based on various definitions: first sign of the disorder, first psychotic symptom and first admission. 62% of the patients with drug abuse and 51% of those with alcohol abuse began the habit before illness onset (=first sign of the disorder). Abuse onset and illness onset occurred highly significantly within the same month (drug abuse in 34.6%, alcohol abuse in 18.2%). Unexpectedly, no temporal correlation was found between abuse onset and the onset of the first psychotic episode. We concluded that a small proportion of schizophrenias might have been precipitated by substance--mainly cannabis--abuse. Long-term effects of early substance abuse were studied prospectively at six cross-sections over five years from first admission on in a subsample of 115 first episodes of schizophrenia. Abusers showed significantly more positive symptoms and a decrease in affective flattening compared with controls. Five-year outcome as based on treatment compliance, utilization of rehabilitative measures and rate of employment was also poorer for patients with than without early substance abuse.