Predictors of treatment response to psychological interventions in people at clinical high risk of first-episode psychosis.

AIM: Psychological interventions, such as cognitive behavioural therapy (CBT) and supportive counselling (SC), are used to treat people with schizophrenia and people at clinical high risk (CHR) of psychosis. However, little information is available on predictors of treatment response. This study aims to identify such predictors of psychological interventions in CHR. METHODS: A total of 128 help-seeking CHR outpatients were randomized into two groups-integrated psychological intervention (IPI), including CBT, and SC-for 12 months. Multiple regression analysis was used to identify demographic, symptomatic and functional variables that predict improvement in positive (PANSS Positive), negative (PANSS Negative) and basic symptoms (Basic symptom total score) and improvement in functioning (GAF) at 1-year follow up. RESULTS: In the merged group (IPI + SC), people who lived independently, were younger and presented with higher baseline functioning showed more improvement in symptomatic outcomes at follow up. Negative symptoms at baseline predicted less improvement in positive and basic symptoms. Being married or cohabiting and living in the primary family were found to correlate with good functioning at 1-year follow up. CONCLUSIONS: Younger CHR individuals and those who are functioning well may particularly benefit from early intervention. Treatment might need to be modified for low-functioning CHR and those who already display higher scores of negative symptoms. Registration number: NCT00204087.

The early recognition inventory ERIraos assesses the entire spectrum of symptoms through the course of an at-risk mental state.

AIM: Functional disability and social consequences frequently occur at the prodromal stage of schizophrenia. Efforts to recognize an increasing risk of psychosis onset have thus become a topical issue worldwide. This is to introduce the English version of the ERIraos early-recognition inventory. METHODS: The ERIraos, developed in a systematic, empirical approach from the Instrument for the Retrospective Assessment of the Onset of Schizophrenia, incorporates basic symptoms from the Cologne Early Recognition Study. The research version also includes as further predictive items so-called brief limited intermittent psychotic symptoms and attenuated psychotic symptoms from the Comprehensive Assessment of At-Risk Mental States instrument. RESULTS: The ERIraos with its 15-item screening Checklist and 50-item Symptom List permits early recognition of psychosis risk in three steps of decreasing sensitivity and increasing specificity. Step 1 relies on patients' self-perception of symptoms, which prompt them to contact a primary health service. There, in Step 2, at-risk individuals are identified using the Checklist, characterized by a low-risk threshold, and referred to further examination using the Symptom List (Step 3). Information on symptom accumulation and increasing symptom severity enhances the instrument's predictive power. In a validation test, psychotic transitions increased linearly up to 50% over 2 years. Compared with other instruments and on the prodromal stage of depressive disorder, the ERIraos has shown good predictive capacity. CONCLUSIONS: The ERIraos has been successfully employed as a two-step tool for the early recognition of psychosis risk in several German studies and translated into several foreign languages.

[Neuropsychological Functioning as a Predictor of Treatment Response to Psychoeducational, Cognitive Behavioral Therapy in People at Clinical High Risk of First Episode Psychosis]. / Neuropsychologische Funktionen als Prädiktoren des Therapieerfolgs von psychoedukativer, kognitiv verhaltenstherapeutischer Therapie bei Personen mit erhöhtem Psychoserisiko.

OBJECTIVE: Investigate whether treatment response in people at clinical high risk of psychosis (CHR) is predicted by their cognitive performance. METHOD: 128 CHR outpatients were randomized into two treatment groups, one receiving integrated psychological intervention (IPI), including psychoeducation, the other receiving supportive counselling (SC) for 12 months. Multiple regression analysis was used to identify neurocognitive predictors of treatment response in a subgroup of n = 105, measured by symptomatic and functional improvement at 1-year follow-up. RESULTS: In the IPI, treatment response was associated with performance of executive control and processing speed (R²â€Š= 0.27, p = 0.002). In both treatment groups, performance of working memory/attention was a significant predictor (IPI: R²â€Š= 0.15, p = 0.039, SC: R²â€Š= 0.19, p = 0.012). CONCLUSION: Cognitive performance is associated with treatment response in CHR people. The enhancement of cognitive performance is a useful target of early intervention.

Shades of vulnerability: latent structures of clinical caseness in prodromal and early phases of schizophrenia.

The underlying structures of clinical caseness and need of care in prodromal (i.e., at-risk) and early phases of schizophrenia remain poorly characterized in their essential psycho-behavioral coherence. To identify the schizophrenia proneness-related subtypes within a population of young help-seekers referred to a dedicated, community-based early detection program (Programma 2000). A sample of consecutive referrals (n = 168) for suspected psychosis or first-episode schizophrenia spectrum psychosis received a detailed clinical assessment, including the early recognition inventory for the retrospective assessment of the onset of schizophrenia checklist. We used exploratory factor analysis (EFA) to determine the underlying dimensional structure and latent class analysis (LCA) to identify putative vulnerability subtypes. EFA identified four factors: dysphoria (irritability tension), paranoid autocentrism, introversive withdrawal, and disturbed subjective experience. LCA distinguished three classes, interpretable as carrying different degrees of "proneness to schizophrenia psychosis," which best captured the underlying continuum of clinical severity. The validity of the three classes was supported by distinct patterns of association with major clinical variables (i.e., diagnostic staging at referral). Vulnerability to schizophrenia psychosis in young help-seekers may manifest in three major clinical prototypes, presenting common levels of dysphoria and social withdrawal but different degrees of paranoid autocentrism and disturbed subjective experience. Overall, the results provide the empirical background to dissect shared features of clinical caseness from more schizophrenia-specific vulnerability components. This is of value for the refinement of the clinical staging model as well as for the pragmatic implementation of multiple-gate screening programs.

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.

Early detection of schizophrenia: current evidence and future perspectives.

RESEARCH INTO THE EARLY COURSE OF SCHIZOPHRENIA HAS IDENTIFIED A PREPSYCHOTIC PRODROMAL STAGE (MEAN DURATION: 4.8 years) and a psychotic prephase (mean duration: 1.3 years). Comparisons of individually matched samples have demonstrated prodromal symptoms common to schizophrenia and moderate to severe depression. It is not until positive symptoms emerge that psychosis and mood disorders become distinguishable from each other. In both disorders the prodromal stage early produces functional impairment and related social consequences. Hence, early intervention is of great public health relevance. This intervention is targeted at manifest symptoms and not at the underlying, still unknown disease process. Cognitive-behavioural therapy at the prepsychotic prodromal stage seems to favourably influence the short-term illness course. In the psychotic prephase, a combination with low-dose antipsychotics seems to have some efficacy. The aim of early recognition by the instruments discussed in this paper is to permit the identification of the largest possible proportion of at-risk persons as early as possible and their referral to appropriate treatment.

[Developmental conditions and subjective experiences of children with a schizophrenic parent--qualitative and quantitative studies from the Mannheim Study of Children at Risk]. / Sozialer Entwicklungsstand und subjektives Belastungserleben bei Nachkommen Schizophrener--Qualitative und quantitative Ergebnisse aus der Mannheimer Risikokinderstudie.

OBJECTIVE: 35 children 12-42 years of age of patients with schizophrenia (ABC-Cohort-12-year-follow-up) were interviewed for studying objective and subjective effects of growing up with a schizophrenic parent. MATERIAL AND METHOD: Social development and childhood experiences were assessed and quantitatively and qualitatively evaluated. RESULTS: The majority of probands had to take on early responsibilities in their family. Experienced deficits in parental care and problems with poor communication within the family were also mentioned. Compared with controls they showed only light disadvantages in the level of education and vocational training. CONCLUSION: Even if early independence could be a positive resource for children with a schizophrenic parent the restrictions in the child's life and development should not be overlooked. Information on the illness and support in dealing with stressful situations are frequently needed.

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.

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

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.

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.