Although cognitive remediation (CR) improves cognition and functioning, the key features that promote or inhibit its effectiveness, especially between cognitive domains, remain unknown. Discovering these key features will help to develop CR for more impact.

To identify interrelations between cognition, symptoms, and functioning, using a novel network analysis approach and how CR affects these recovery outcomes.

A secondary analysis of randomized controlled trial data (N = 165) of CR in early psychosis. Regularized partial correlation networks were estimated, including symptoms, cognition, and functioning, for pre-, post-treatment, and change over time. Pre- and post-CR networks were compared on global strength, structure, edge invariance, and centrality invariance.

Cognition, negative, and positive symptoms were separable constructs, with symptoms showing independent relationships with cognition. Negative symptoms were central to the CR networks and most strongly associated with change in functioning. Verbal and visual learning improvement showed independent relationships to improved social functioning and negative symptoms. Only visual learning improvement was positively associated with personal goal achievement. Pre- and post-CR networks did not differ in structure (M = 0.20, p = 0.45) but differed in global strength, reflecting greater overall connectivity in the post-CR network (S = 0.91, p = 0.03).

Negative symptoms influenced network changes following therapy, and their reduction was linked to improvement in verbal and visual learning following CR. Independent relationships between visual and verbal learning and functioning suggest that they may be key intervention targets to enhance social and occupational functioning.

Risk of psychosis is defined by the presence of positive psychotic-like symptoms. In clinical examination, easily detectable perceived negative attitude of other people may also indicate risk of psychosis.

A random sample of psychiatric outpatients completed the PROD screen including questions on interpersonal relationships, functioning and subtle specific (psychotic-like) symptoms. Vulnerability to psychosis (VTP) was assessed employing specific symptoms of the PROD screen. Current risk of psychosis (CROP) was assessed using the BSABS and the SIPS/SOPS. The CROP patients were followed up for 18 months and transition to psychosis was detected. The association between perceived negative attitude of others and reported psychotic symptoms was tested in a random sample drawn from the general population.

In all, 790 outpatients were screened. Of them, 219 VTP and 55 CROP patients were identified. By follow-up, six CROP patients (11 %) had made the transition to psychosis. Vulnerability to psychosis associated with all items of interpersonal relationships and functioning. However, current risk and transition to psychosis associated only with subjectively reported negative attitude of others. In a general population sample, negative attitude of others strongly associated with reported life-time psychotic symptoms conforming thus results obtained from a patient sample.

The subjective experience of negative attitude of other people towards oneself associates with experience of psychotic symptoms and may predict more sever psychotic development. The association between perceived negative attitude and occurrence of subtle psychotic symptoms seems to be detectable both in general and patient populations.

Despite remission being the primary objective following the first episode of schizophrenia, clinically stabilised patients are rarely studied.

To assess the extent and fluctuation of low-level positive symptoms in patients who are in remission following their first episode of schizophrenia, and consider whether symptoms displayed are similar to those exhibited in the prodromal population.

Eleven patients who had recovered for at least six months following one episode of schizophrenia and subsequently fulfilled remission criteria were interviewed four times over the course of three months. Interviews were based on the Structured Interview of Prodromal Symptoms (SIPS), an in-depth assessment of low-level symptoms that is widely used in the prodromal group. Data was compared to equivalent results from the prodromal population (with data provided by the local ED:IT service).

Over the course of the interviews 73% of participants displayed attenuated positive symptoms, predominantly unusual thought content and suspiciousness. 18% experienced brief limited intermittent psychotic symptoms (BLIPS). Analysis with Friedman's test revealed no significant fluctuation in positive symptoms, indicating that they are stable over time. Furthermore, the symptoms exhibited in the sample were closely comparable to those in the prodromal group in the ED:IT service.

The majority of patients in remission are experiencing a form of ‘postdrome’, which appears to be an enduring state. the presence of these symptoms may put patients at an increased risk of relapse. Larger-scale research is required to follow-up this novel preliminary study.

None.

The European Prediction of Psychosis Study (EPOS) aimed to study a large sample of young patients who are at risk of psychosis and to estimate their conversion rate to psychosis during 18 months follow-up. This presentation describes quality of life and its changes in patients at risk of psychosis.

In six European centres, 16 to 35 year old psychiatric patients were examined. Risk of psychosis was defined by occurrence of basic symptoms, attenuated psychotic symptoms, brief, limited or intermittent psychotic symptoms or familial risk plus reduced functioning. Quality of life (QoL), measured by the Modular System for Quality of Life, was assessed at baseline and at 9 and 18 months’ follow-ups. Psychiatric patients without prodromal symptoms and healthy subjects were comparison groups.

In all, 245 risk patients were included. At baseline, they reported lower QoL than non-risk patients and healthy controls. Basic symptoms associated negatively with QoL, and there were differences between the study centres. During the follow-up, QoL raised less in risk patients than in non-risk patients. Baseline QoL did not predict transition to psychosis. However, its development was poorer in patients with than in those without transition to psychosis.

Those of the psychiatric patients who are at risk of psychosis have lower QoL than other psychiatric patients or healthy controls. QoL does not predict transition to psychosis, but its changes correlates with changes in clinical state. The results indicate that there is a need for comprehensive intervention with the patients at risk of psychosis.

Both schizophrenia and ultra high risk (UHR) patients show reduced neurocognitive performance compared to matched healthy control subjects. In the current study we compared neurocognitive performance at baseline and follow up between UHR patients who made the transition to psychosis and patients who did not.

Patients were eligible for the study when they met criteria for one or more of the following groups: Attenuated symptoms or brief limited intermitted psychotic symptoms or a first degree family member with a psychotic disorder and reduced functioning or basic symptoms. We assessed 216 UHR patients (166 males, mean age: 22,6 SD 5,2) with a neuropsychological test battery composed of the National adult reading test (premorbid IQ), California verbal memory test (verbal memory), spatial working memory test, verbal fluency first letter and categories (executive functioning), finger tapping test (motor speed) and continuous performance test (sustained attention). Data were collected in 7 participating centres of EPOS. Follow up was at 9 months.

37 UHR patients made the transition to psychosis (25 males, mean age 21,5 SD 4,8). The only test that showed a significant difference between the transition and non transition group at baseline was verbal fluency categories (t= 2.79, p = 0.006).

Patients who later make the transition to psychosis perform significantly worse on verbal fluency categories than patients who do not make the transition to psychosis. Verbal fluency may contribute to an improved prediction of psychosis in UHR patients. Follow up results will also be presented.

The European Prediction of Psychosis Study (EPOS) involved a large (n=245) sample of young individuals at high-risk of developing psychosis. Participants appraisals of criticism and emotional over-involvement were described employing the Level of Expressed Emotion (LEE) measure. This presentation explores results and implications over an 18 month follow-up period.

Across six European centres, n=245 patients aged 16 – 35 years and ascertained to be at high-risk of developing psychosis were assessed over a period of eighteen months. Risk of psychosis was defined by occurrence of basic symptoms, attenuated psychotic symptoms, brief, limited or intermittent psychotic symptoms or familial risk plus reduced functioning. Appraisals of familial expressed emotion from participants towards key family members were examined for relationships to risk of transition to psychosis, psychotic symptomatology and demographical data.

Individuals at high-risk of psychosis were included and compared on the five sub-scales of LEE. Levels of Criticism, Irritability, Intrusiveness and Lack of emotional support were examined with significant correlations found between patient-perceived intrusive over-involvement and depression as well as between sub-scales of LEE and positive symptoms of psychosis. Transition to psychosis was not predicted by LEE in participants.

Perceived LEE of significant others by individuals at high-risk of developing psychosis may have a role in the maintenance of both affective and positive psychotic symptoms prior to the onset of full psychosis. Further explorations of the impact of EE appraisal on developing psychotic symptoms may inform potential targets for therapeutic intervention in both at-risk individuals and family members.

In the European Prediction of Psychosis Study (EPOS) a large sample of young patients at high risk of psychosis (HR) were examined and their conversion rate to psychosis during 18 months follow-up was estimated. This presentation describes quality of life (QoL) and its changes in patients at risk of psychosis who did or did not convert to psychosis.

In all, 245 young HR patients were recruited and followed for 9 and 18 months. Risk of psychosis was defined by occurrence of basic symptoms (BS), attenuated psychotic symptoms (ATP), brief, limited or intermittent psychotic symptoms (BLIPS) or familial risk plus reduced functioning (FR-RF). QoL was assessed at baseline and at 9 and 18 months’ follow-ups, and analysed in the HR-patients who converted (HR-P; n = 40) or did not converted to psychosis (HR-NP; n = 205).

There were no differences in the course of QoL between the HR-P and HR-NP patients. Of the inclusion criteria, only BS associated with poor QoL at baseline. Among HR-NP subjects, depressive symptoms associated with QoL at baseline and predicted poor QoL at 9 and 18 month follow-ups.

QoL of the HR-NP patients is as poor as that of the HR-P. From the QoL point of view, all HR patients require intensive treatment intervention from the first contact on. Especially, depressive disorders need to be treated vigorously.

Research on at-risk states of psychosis has mainly aimed to predict conversion. Yet as a considerable number of patients does not to progress to this outcome during the investigated observation periods, the course of these non-converters (NC) is of major interest, particularly with regard to preventive interventions and treatment.

To analyze the psychopathological and functional in 18-month non-converters.

Data were derived from the prospective multicenter European Prediction of Psychosis Study with an 18-month follow-up period. Participants had to fulfill ultra-high risk criteria and/or the COGDIS criterion, which is based on a set of cognitive basic symptoms. Psychopathology was assessed with the Structure Interview for Prodromal Syndromes (SIPS), including the Global Assessment of Functioning Scale (GAF) and a short version of the Schizophrenia Proneness Instrument (SPI-A).

All total and subscale scores improved significantly during follow-up. However, a more detailed analysis revealed that a considerable part of the patients showed no improvement or even a worsening of psychopathology and function.

Our first analysis of course on non-converters shows that a high proportion of patients improved. In the light of results from retrospective studies, however, this improvement has to be interpreted with caution, as the observation period does not allow to determine the proportion of outpost syndromes, i.e. precursors of a later prodrome. Furthermore, a considerable portion of our sample worsened functionally and/or symptomatically. With regard to retrospective schizophrenia related results, very long observation periods may be needed to characterize the patterns of course in subpsychotic syndromes.

Early detection and indicated early intervention in the initial prodromal phase should considerably improve the course of psychoses. Yet, the benefits of such programmes still require an evidence-based evaluation on the basis of a sufficient sample-size.

This report presents an overview on the concept and design of the European Prediction of Psychosis Study (EPOS) an European 4-country naturalistic field-study of the initial Prodrome.

Across six participating centres (Germany: Cologne, Berlin; Finland: Turku; The Netherlands: Amsterdam; United Kingdom: Birmingham, Manchester), 16 to 40 year old putatively prodromal persons attending specialized services or general psychiatric services underwent multi-level baseline, 9-months follow-up, and 18-months follow-up examinations. Inclusion criteria were the presence of APS, BLIPS, at least 2 of 9 Basic Symptoms (BS), and Familial Risk or Schizotypal Personality Disorder plus Reduced Functioning (FR+RF). In addition, psychopathological, neurocognitive, neurobiological, psychosocial, and service and treatment-related assessments were carried out.

A substantial part of more than 250 subjects included into the study participated in their respective baseline, 1st follow-up, and 2nd follow-up examinations. A high percentage presented themselves with BS and/or APS, a smaller percentage with BLIPS or FR+RF. The rates of transition into psychosis and the levels of psychopathology, distress and functional decline found among this patient group underline the need for indicated early recognition and intervention.

EPOS provides for the first time a sound data base allowing an evaluation of the applicability and cost-benefit ratio of early detection and intervention programmes in Europe.

Theoretically, schizotypal features should be prevalent in patients at ultra high risk of psychosis. In connection to the European Prediction of Psychosis Study (EPOS), we could study their prevalence in this group using three different ways of assessing schizotypality.

EPOS dataset comprises a large sample (n=246) of UHR patients, who were followed up for 18 months. Schizotypal features were assessed in connection to SIPS interview (SIPS-STY, researcher assessment), and with PDQ-R and SPQ scales (self-assessment). Descriptive data and intercorrelations between different measures are described. Concurrent validity of these three measures is assessed by externals validators (genetic risk/ neuropsychology).

The prevalence of schizotypal pdo was 13.4% with SIPS-STY and 34.6% with PDQ-R-STY. These categorial measures were poorly correlated (k=0,11). Of continuous measures PDQ-R-STY and SPQ scores were highly correlated (r=0,78, P<,000), but SIPS-STY score was only weakly correlated with these other measures (r=0.24).

As to external validation, FDRs of psychotics did not differ from other subjects on the level of schizotypal features. PDQ-R-STY but not SIPS-STY was associated with lower verbal IQ (P=0.004). In verbal fluency test, both SIPS-STY and PDQ-R-STY contributed to poor performance, but SPQ did not add to this. Schizotypal status did not associate with results of the Spatial working memory paradigm (SWMT).

Different measures of schizotypality produce somewhat inconsistent results when studied in a high psychosis risk sample. PDQ-R questionnaire seemed to give results most consistent with the current notion of schizotypicality.

The main aim of the European Prediction of Psychosis Study (EPOS) is to study a large sample of young patients who are at risk of psychosis and to estimate their conversion rate to psychosis during 18 months follow-up. The present presentation aims to describe premorbid adjustment in the patients at risk of psychosis.

In six European centres (Cologne, Berlin, Turku, Amsterdam, Birmingham, Manchester), 246 psychiatric patients at risk of psychosis were examined. Risk of psychosis was defined by occurrence of basic symptoms, attenuated psychotic symptoms, brief, limited or intermittent psychotic symptoms or familial risk plus reduced functioning during the past three months. Premorbid adjustment was measures by the Premorbid Adjustment Scale (PAS) and correlated with patient's baseline and outcome measures. Psychiatric patients without prodromal symptoms (not at risk) and healthy subjects, studied in one centre, acted as comparison groups.

PAS scores were poorer in the patients at risk of psychosis than in patients without prodromal symptoms or in healthy controls. In adolescence, differences in PAS scores were greater than in childhood or in adulthood. Within patients at risk of psychosis, men had poorer PAS scores than women. Childhood, adolescent and adulthood PAS scores associated extensively with patient's clinical and functional state at baseline examination. Adolescent and adulthood PAS scores correlated also with conversion to psychosis.

Disturbed premorbid psychosocial development, especially from adolescence on, may indicate vulnerability to and onset of psychosis.

Evidence from long-term follow-up studies of schizophrenia and from the ‘new epidemiology’ of psychoses has forced us to rewrite the textbooks and challenge accepted wisdom. In this paper I aim to review the concept of my ‘Critical Period’ in the long-term trajectory of schizophrenia.

I will review long-term follow-up studies of first episode psychosis.

Studies suggest that:

1. a. the course of the psychoses is very variable;

2. b. much of this variability is laid down during the ‘prodromal’ and first 3 - 5 years following the first episode;

3. c. the ‘disability’ plateaus quickly, much of it occuring before the positive symptoms develop (the ‘symptom-disability gap’) but

4. d. the psychosocial and ecological risk factors that have now been uncovered, suggest a more protean, malleable process in the development of psychosis, as witnessed, for example by the considerable number of ‘at risk’ individuals with low-level, but disabling psychotic symptoms, who escape psychosis (the misnomer of the ‘false positive’).

This picture presents a fresh take on my concept of the ‘critical period’ with implications for public health and prevention.

A main objective of EPOS is to provide a valid multifactorial model for the prediction of psychosis. One major element of such a model should be the clinical state.

In a European multicentre study, persons fulfilling clinical criteria thought to indicate an increased risk for psychosis (PAR) were assessed amongst others with different psychopathological instruments covering the whole spectrum from basic symptoms to frank psychotic symptoms. Inclusion criteria comprised attenuated positive symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS), cognitive basic symptoms (CogDis) and a combination of family risk and reduced functioning (S&T).

246 PAR were included into the study, mostly by APS or CogDis. Analysis of demographical data showed a high amount of functional impairment, resulting e.g. in low mean GAF scores (51.0 ± 11.8 SD), and of non-psychotic axis-I disorders. In September 2006, the hazard rate for a conversion to psychosis was 15.3 at 12 and 20.0 at 18 months after baseline assessment. According to the inclusion criteria, the highest rate of conversion was observed among PAR with BLIPS. On a dimensional level, a low GAF score was among the best predictors of conversion.

The transition rates of EPOS were in line with recent studies. A first analysis of clinical data supports the notion that the functional state should be an inherent part of any set of clinical risk criteria. Further analysis will consider the contribution of single symptoms or symptom combinations and the impact of symptom duration.

One aim of the European prediction of psychosis study (EPOS) has been to evaluate the clinical course of putatively prodromal patients in terms of psychopathology.

245 patients at risk for psychosis defined by attenuated positive symptoms, brief limited psychotic symptoms, a state/ trait combination or cognitive-perceptive basic symptoms was recruited in six centres in four countries. The Structured Interview for Prodromal Syndromes (SIPS) and the Bonn Scale for the Assessment of Basic Symptoms – Prediction List (BSABS-P) were employed. Follow-up was scheduled after 9 months (t1) and 18 months.

In total, 40 patients developed a psychosis (P). Compared to those without a transition (NP), P showed significantly higher SIPS scores at baseline. The same applied to the BSABS-P sub-scores 'cognitive perception disturbances' and 'cognitive motor disturbances'. The P sub-group developing psychosis after t1 showed no significant change of the SIPS positive (SIPS-P) sub-score or of any BSABS-P score from baseline to t1, whereas all scores improved in the NP group. At t1, SIPS-P and BSABS-P sub-score 'cognitive thought disturbances' were significantly lower in those later becoming psychotic.

Patients at risk showing a transition to psychosis during exhibited a pronounced psychopathology at baseline. Also, the positive symptom scores did not significantly improve during 1st follow-up, whereas those patients with no transition during the complete follow-up showed an improvement of all scores. As EPOS is a naturalistic study, different treatments have been performed in a considerable portion of the patients and association with course awaits further analysis.

In patients with schizophrenia, premorbid psychosocial adjustment is an important predictor of functional outcome. We studied functional outcome in young clinical high-risk (CHR) patients and how this was predicted by their childhood to adolescence premorbid adjustment.

In all, 245 young help-seeking CHR patients were assessed with the Premorbid Adjustment Scale, the Structured Interview for Prodromal Syndromes (SIPS) and the Schizophrenia Proneness Instrument (SPI-A). The SIPS assesses positive, negative, disorganised, general symptoms, and the Global Assessment of Functioning (GAF), the SPI-A self-experienced basic symptoms; they were carried out at baseline, at 9-month and 18-month follow-up. Transitions to psychosis were identified. In the hierarchical linear model, associations between premorbid adjustment, background data, symptoms, transitions to psychosis and GAF scores were analysed.

During the 18-month follow-up, GAF scores improved significantly, and the proportion of patients with poor functioning decreased from 74% to 37%. Poor premorbid adjustment, single marital status, poor work status, and symptoms were associated with low baseline GAF scores. Low GAF scores were predicted by poor premorbid adjustment, negative, positive and basic symptoms, and poor baseline work status. The association between premorbid adjustment and follow-up GAF scores remained significant, even when baseline GAF and transition to psychosis were included in the model.

A great majority of help-seeking CHR patients suffer from deficits in their functioning. In CHR patients, premorbid psychosocial adjustment, baseline positive, negative, basic symptoms and poor working/schooling situation predict poor short-term functional outcome. These aspects should be taken into account when acute intervention and long-term rehabilitation for improving outcome in CHR patients are carried out.

A considerable number of patients at clinical high risk of psychosis (CHR) are found to meet criteria for co-morbid clinical psychiatric disorders.

It is not known how clinical diagnoses correspond to transitions to psychosis (TTP).

We aimed to examine distributions of life-time and current Axis I diagnoses, and their association with TTP in CHR patients.

In the European Prediction of Psychosis Study project, 245 young help-seeking CHR patients were examined, and their baseline and life-time diagnoses were assessed by the Structured Clinical Interview for DSM-IV (SCID-I). TTP was defined by continuation of BLIPS for more than seven days.

Altogether, 71 % of the CHR patients had one or more life-time and 62 % one or more current SCID-I diagnosis; about a half in each category received a diagnosis of life-time depressive and anxiety disorder. Currently, 34 % suffered from depressive, 39 % from anxiety disorder, 4 % from bipolar and 6.5 % from somatoform disorder. During follow-up, 37 (15.1 %) TTPs were identified. In multivariate Cox regression analyses, current bipolar disorder, somatoform and unipolar depressive disorders associated positively, and anxiety disorders negatively, with TTP.

Both life-time and current mood and anxiety disorders are highly prevalent among help-seeking CHR patients and need to be carefully evaluated. Among them, occurrence of bipolar, somatoform and depressive disorders seem to predict TTP, while anxiety disorder may predict non-transition to psychosis. Treatment of bipolar, somatoform and depressive disorders may prevent CHR patients from developing full-blown psychotic disorders.

Ultra-high risk (UHR) criteria are defined by attenuated and/or transient full-blown psychotic symptoms and/or a combination of genetic risk factor and deterioration of functioning. To achieve a higher predictive specificity and a clear threshold of clinical importance, functional impairment has been considered as an obligate part of all UHR criteria.

In the European Prediction of Psychosis Study (EPOS)N = 37 participants converted to psychosis, n = 146 completed the whole 18-month follow-up period without conversion. Assessed by the Global Assessment of Functioning Scale, modified version (GAF-M), the following functional states were considered: Considered GAF-M: ≤30%/≤10% reduction of baseline scores related to highest scores in the previous year; scores ≤70/≤60.

The GAF reduction criteria led to a very unfavorable loss of sensitivity, even, if only 10% were demanded. This was accompanied by correspondingly unfavorable accuracy measures. Introducing functional impairment criteria defined by the current state reported to be predictive for psychiatric caseness (score ≤ 70) or to define serious impairment (score ≤ 60) (Kessler et al., 2002, 2003) kept sensitivity at a perfectly high level, yet did not produce any gain of specificity.

These results were certainly be caused by the fact that the whole group showed already low GAF-M scores in the previous year. Thus, a functional impairment criterion proved not to be useful to improve prediction. However, a combination of APS or BLIPS with a ‘clinical status’ criterion of GAF-M ≤ 70 may be considerable to demonstrate a strong need for intervention.

Our previous study (Salokangas et al., 2009) suggested that the subjective experience of negative attitude of others (NAO) towards oneself is an early indicator of psychotic development. The aim of this prospective follow-up study was to test this hypothesis.

A total of 55 young psychiatric outpatients assessed as being at current risk of psychosis (CROP) were followed for up to 60 months and rates of transition to psychosis (TTP) identified. CROP was assessed employing the Bonn Scale for assessment of basic symptoms (Schultze-Lutter and Klosterkötter, 2002) and the Structured Interview for prodromal symptoms (Miller et al., 2002). TTP was defined by a psychotic episode lasting for more than one week. Associations between NAO at baseline and TTP were analyzed by a Cox regression survival analysis.

Eight (14.5%) TTP were identified: four (57.1%) within seven NAO patients and four (8.7%) within forty-six non-NAO patients. In the multivariate Cox regression analysis, NAO at baseline significantly (P = 0.007) predicted TTP.

The prospective follow-up results support our hypothesis that subjective experience of NAO is an early indicator of psychotic in development.