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.

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.

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.

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.

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.

The link between depression and paranoia has long been discussed in the psychiatric literature. Because this association is difficult to study in patients with full-blown psychosis, we investigated clinical high-risk (CHR) patients.

To clarify the causal connection between depression and paranoia.

To investigate how clinical depression relates to presence and new occurrence of paranoid symptoms in CHR patients.

Altogether, 245 young help-seeking CHR patients were assessed for suspiciousness/paranoid symptoms with the Structured Interview for Prodromal Syndromes at baseline, 9-month and 18-month follow-up. At baseline, clinical diagnoses were assessed by the Structured Clinical Interview for DSM-IV, childhood stressful experiences by the Trauma and Distress Scale, trait of suspiciousness by the Schizotypal Personality Questionnaire, and anxiety and depressive symptoms by the Positive and Negative Syndrome Scale.

At baseline, 54.3 % of CHR patients reported at least moderate paranoid symptoms. At 9- and 18-month follow-ups, the corresponding figures were 28.3 % and 24.4 %. Depressive disorder, sexual abuse and anxiety symptoms associated with paranoid symptoms. Depressive, obsessive-compulsive and somatoform disorders, sexual abuse, and anxiety predicted occurrence of paranoid symptoms.

Depressive disorder is one of the major clinical factors associating with and predicting paranoid symptoms in CHR patients; also childhood sexual abuse and anxiety symptoms associate with paranoia. In addition, obsessive-compulsive and somatoform disorders seem to predict paranoid symptoms. Low self-esteem may be a common mediator between affective disorders and paranoia. Effective treatment of these disorders may alleviate paranoid symptoms and improve interpersonal functioning in CHR patients.

Depressive and anxiety disorders are the most common clinical diagnoses in patients at clinical high-risk (CHR) of psychosis (1).

Clinical disorders and functioning in CHR patients.

To study how depressive and anxiety disorders associate with patients’ functioning at baseline and follow-ups in CHR patients.

In the EPOS project, 245 young help-seeking CHR patients were examined, and their baseline diagnoses were assessed by the SCID-I. The patients were interviewed with the SIPS/SOPS, including assessments of positive and negative symptoms and the Global Assessment of Function (GAF), at baseline and at 9 and 18 months follow-ups.

At baseline and follow-ups, the patients without depressive or anxiety disorders had highest GAF scores. At baseline, the patients with depressive disorders had lower GAF scores than the patients with anxiety disorders. At follow-ups, there were no differences in GAF scores between the patients with depressive or anxiety disorders. In modelling, negative symptoms associated with low GAF scores at baseline and follow-ups, positive symptoms only at baseline and anxiety disorders at 18 months follow-up.

Depressive and anxiety disorders associate with poor functional outcome, and require thus special attention when intervention for the CHR patients is carried out. Positive symptoms predict transition to psychosis (2), but their role in predicting functional outcome is not as great. Instead, negative symptoms associate with poor functional outcome and require intensive intervention.

1. (1) Salokangas RKR et al. Schizophr Res 2012, doi:10.1016/j.schres.2012.03.008.

2. (2) Ruhrmann S et al. Arch Gen Psychiatry 2010;67:241-251.

Schizotypal features indicate proneness to psychosis in the general population. It is also possible that they increase transition to psychosis (TTP) among clinical high-risk patients (CHR). Our aim was to investigate whether schizotypal features predict TTP in CHR patients.

In the EPOS (European Prediction of Psychosis Study) project, 245 young help-seeking CHR patients were prospectively followed for 18 months and their TTP was identified. At baseline, subjects were assessed with the Schizotypal Personality Questionnaire (SPQ). Associations between SPQ items and its subscales with the TTP were analysed in Cox regression analysis.

The SPQ subscales and items describing ideas of reference and lack of close interpersonal relationships were found to correlate significantly with TTP. The co-occurrence of these features doubled the risk of TTP.

Presence of ideas of reference and lack of close interpersonal relations increase the risk of full-blown psychosis among CHR patients. This co-occurrence makes the risk of psychosis very high.

The association between parental severe mental illness (SMI) and depression in offspring may be due to genetic liability or adverse environments. We investigated the effect of parental SMI, SES, and adversity on depression in a sample of youth enriched for familial risk of mental illness.

We assessed 217 youth (mean age 11.95, SD 4.14, range 6–24), including 167 (77%) offspring of parents with SMI. We measured exposure to childhood maltreatment and bullying with the Juvenile Victimization Questionnaire (JVQ) and Childhood Experiences of Care and Abuse (CECA) interview.

In total, 13.36% participants reported significant bullying and 40.76% had a history of childhood maltreatment. Rates of bullying and maltreatment were similar in offspring of parents with and without SMI. Maltreatment likelihood increased with decreasing socioeconomic status. Exposure to bullying (OR = 3.11, 95%CI 1.08–8.88, P = 0.03) predicted depression in offspring more strongly than family history of SMI in parents.

Adversity, such as maltreatment and bullying, has a stronger impact on the risk of developing depression than family history of mental illness in parents. These adverse experiences are associated with socioeconomic status rather than parental mental illness.

The authors have not supplied their declaration of competing interest.

Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state.

Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders.

Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia.

Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.