Adverse childhood experiences (ACE) can affect educational attainments, but little is known about their impact on educational achievements in people at clinical high risk of psychosis (CHR).

In total, 344 CHR individuals and 67 healthy controls (HC) were recruited as part of the European Community’s Seventh Framework Programme-funded multicenter study the European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI). The brief version of the Child Trauma Questionnaire was used to measure ACE, while educational attainments were assessed using a semi-structured interview.

At baseline, compared with HC, the CHR group spent less time in education and had higher rates of ACE, lower rates of employment, and lower estimated intelligence quotient (IQ). Across both groups, the total number of ACE was associated with fewer days in education and lower level of education. Emotional abuse was associated with fewer days in education in HC. Emotional neglect was associated with a lower level of education in CHR, while sexual abuse was associated with a lower level of education in HC. In the CHR group, the total number of ACE, physical abuse, and neglect was significantly associated with unemployment, while emotional neglect was associated with employment.

ACE are strongly associated with developmental outcomes such as educational achievement. Early intervention for psychosis programs should aim at integrating specific interventions to support young CHR people in their educational and vocational recovery. More generally, public health and social interventions focused on the prevention of ACE (or reduce their impact if ACE occur) are recommended.

Clinical high-risk states for psychosis (CHR) are associated with functional impairments and depressive disorders. A previous PRONIA study predicted social functioning in CHR and recent-onset depression (ROD) based on structural magnetic resonance imaging (sMRI) and clinical data. However, the combination of these domains did not lead to accurate role functioning prediction, calling for the investigation of additional risk dimensions. Role functioning may be more strongly associated with environmental adverse events than social functioning.

We aimed to predict role functioning in CHR, ROD and transdiagnostically, by adding environmental adverse events-related variables to clinical and sMRI data domains within the PRONIA sample.

Baseline clinical, environmental and sMRI data collected in 92 CHR and 95 ROD samples were trained to predict lower versus higher follow-up role functioning, using support vector classification and mixed k-fold/leave-site-out cross-validation. We built separate predictions for each domain, created multimodal predictions and validated them in independent cohorts (74 CHR, 66 ROD).

Models combining clinical and environmental data predicted role outcome in discovery and replication samples of CHR (balanced accuracies: 65.4% and 67.7%, respectively), ROD (balanced accuracies: 58.9% and 62.5%, respectively), and transdiagnostically (balanced accuracies: 62.4% and 68.2%, respectively). The most reliable environmental features for role outcome prediction were adult environmental adjustment, childhood trauma in CHR and childhood environmental adjustment in ROD.

Findings support the hypothesis that environmental variables inform role outcome prediction, highlight the existence of both transdiagnostic and syndrome-specific predictive environmental adverse events, and emphasise the importance of implementing real-world models by measuring multiple risk dimensions.

The high prevalence of smoking in individuals who are at ultra-high risk (UHR) for psychosis is well known and moderate cognitive deficits have also been found in UHR. However, the association between smoking and cognition in UHR is unknown and longitudinal studies are lacking.

A cohort study with 330 UHR individuals and 66 controls was conducted, as part of the European network of national schizophrenia networks studying gene–environment interactions (EU-GEI). At baseline and after 6, 12, and 24 months, smoking behavior was assessed with the Composite International Diagnostic Interview and cognitive functioning with a comprehensive test battery. Linear mixed-effects analyses were used to examine the multicross-sectional and prospective associations between (change in) smoking behavior and cognitive functioning, accounting for confounding variables.

At baseline, 53% of UHR and 27% of controls smoked tobacco. Smoking UHR and controls did not significantly differ from nonsmoking counterparts on the tested cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, or reasoning/problem solving) across different assessment times. Neither smoking cessation nor initiation was associated with a significant change in cognitive functioning in UHR.

No associations were found between smoking and cognitive impairment in UHR nor in controls. However, the fact that one in every two UHR individuals report daily use of tobacco is alarming. Our data suggest that UHR have fewer cognitive impairments and higher smoking cessation rates compared to patients with first-episode psychosis found in literature. Implications to promote smoking cessation in the UHR stage need further investigation.

Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure.

We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry.

(i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains ‘emotional neglect’ and ‘emotional abuse’ were most predictive for CHR and ROP, while in ROD ‘physical abuse’ and ‘sexual abuse’ were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found.

These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis.

Psychosis is associated with a reasoning bias, which manifests as a tendency to ‘jump to conclusions’. We examined this bias in people at clinical high-risk for psychosis (CHR) and investigated its relationship with their clinical outcomes.

In total, 303 CHR subjects and 57 healthy controls (HC) were included. Both groups were assessed at baseline, and after 1 and 2 years. A ‘beads’ task was used to assess reasoning bias. Symptoms and level of functioning were assessed using the Comprehensive Assessment of At-Risk Mental States scale (CAARMS) and the Global Assessment of Functioning (GAF), respectively. During follow up, 58 (16.1%) of the CHR group developed psychosis (CHR-T), and 245 did not (CHR-NT). Logistic regressions, multilevel mixed models, and Cox regression were used to analyse the relationship between reasoning bias and transition to psychosis and level of functioning, at each time point.

There was no association between reasoning bias at baseline and the subsequent onset of psychosis. However, when assessed after the transition to psychosis, CHR-T participants showed a greater tendency to jump to conclusions than CHR-NT and HC participants (55, 17, 17%; χ2 = 8.13, p = 0.012). There was a significant association between jumping to conclusions (JTC) at baseline and a reduced level of functioning at 2-year follow-up in the CHR group after adjusting for transition, gender, ethnicity, age, and IQ.

In CHR participants, JTC at baseline was associated with adverse functioning at the follow-up. Interventions designed to improve JTC could be beneficial in the CHR population.

The establishment phase of an early detection centre for prodromal psychosis is introduced and characterised, along with its detaining and promoting factors within a universal multi-payer health care system.

Across the first six years (1998–2003), users' characteristics are compared between different diagnostic groups and to the local population statistics; and, for an exemplary 12-months period (3-1-2002 to 2-28-2003), the characteristics of telephone contacts with the service are studied.

Rising steadily in number across the first three years, 872 persons, predominately of German citizenship and higher education, consulted the service until 2003, 326 with first-episode psychosis and 144 not fulfilling criteria for a current or beginning psychosis. Of the 402 putatively prodromal patients, 94% reported predictive basic symptoms, 68.9% attenuated and 20.6% transient psychotic symptoms. Most contacts by persons meeting any prodromal criterion were initiated by mental health professionals (psychiatrists or psychologists) and counselling services.

Supported by public awareness campaigns, an early detection service is well received by its users and private practitioners as reflected by the large proportion of referrals from the latter. However, persons of non-German background as well as of lower education were underrepresented indicating that these sub-groups should be approached by tailored programmes.

Risk of psychosis is defined by the presence of positive psychotic-like symptoms, by subtle self-perceived cognitive and perceptual deficiencies, or by decreased functioning with familial risk of psychosis. We studied the associations of psychiatric outpatients' self-reported functioning and interpersonal relationships with vulnerability to and risk of psychosis.

A total of 790 young patients attending psychiatric outpatient care completed the PROD screen [Heinimaa M, Salokangas RKR, Ristkari T, Plathin M, Huttunen J, Ilonen T, et al. PROD-screen – a screen for prodromal symptoms of psychosis. Int J Meth Psychiatr Res 2003;12:92–04.], including questions on functioning, interpersonal relationships and subtle specific (psychotic-like) and non-specific symptoms. Vulnerability to psychosis was assessed employing the patient's written descriptions of specific symptoms. Of the patients vulnerable to psychosis, those at current risk of psychosis were assessed using the Bonn Scale for Assessment of Basic Symptoms [Schultze-Lutter F, Klosterkötter J. Bonn scale for assessment of basic symptoms – prediction list, BSABS-P. Cologne: University of Cologne; 2002] and the Structured Interview for Positive symptoms [Miller TJ, McGlashan TH, Rosen JL, Somjee L, Markovich PJ, Stein K, et al. Prospective diagnosis of the initial prodrome for schizophrenia based on the structured interview for prodromal syndromes: preliminary evidence of interrater reliability and predictive validity. Am J Psychiatry 2002;159:863–65.].

In all, 219 patients vulnerable to and 55 patients at current risk of psychosis were identified. Vulnerability to psychosis was associated with all items of functioning and interpersonal relationships. Current risk of psychosis, however, was associated only with the subjectively reported negative attitude of others. Negative attitude of others was also associated with feelings of reference at both vulnerability and risk levels.

The subjective experience of negative attitude of others towards oneself may be an early indicator of psychotic development.

Sex differences in cognitive functioning have long been recognized in schizophrenia patients and healthy controls (HC). However, few studies have focused on patients with an at-risk mental state (ARMS) for psychosis. Thus, the aim of the present study was to investigate sex differences in neurocognitive performance in ARMS patients compared with HC.

The data analyzed in this study were collected within the multicenter European Gene–Environment Interactions study (11 centers). A total of 343 ARMS patients (158 women) and 67 HC subjects (33 women) were included. All participants completed a comprehensive neurocognitive battery. Linear mixed effects models were used to explore whether sex differences in cognitive functioning were present in the total group (main effect of sex) and whether sex differences were different for HC and ARMS (interaction between sex and group).

Women performed better in social cognition, speed of processing, and verbal learning than men regardless of whether they were ARMS or HC. However, only differences in speed of processing and verbal learning remained significant after correction for multiple testing. Additionally, ARMS patients displayed alterations in attention, current IQ, speed of processing, verbal learning, and working memory compared with HC.

Findings indicate that sex differences in cognitive functioning in ARMS are similar to those seen between healthy men and women. Thus, it appears that sex differences in cognitive performance may not be specific for ARMS, a finding resembling that in patients with schizophrenic psychoses.

Gender differences in symptomatology in chronic schizophrenia and first episode psychosis patients have often been reported. However, little is known about gender differences in those at risk of psychotic disorders. This study investigated gender differences in symptomatology, drug use, comorbidity (i.e. substance use, affective and anxiety disorders) and global functioning in patients with an at-risk mental state (ARMS) for psychosis.

The sample consisted of 336 ARMS patients (159 women) from the prodromal work package of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI; 11 centers). Clinical symptoms, drug use, comorbidity and functioning were assessed at first presentation to an early detection center using structured interviews.

In unadjusted analyses, men were found to have significantly higher rates of negative symptoms and current cannabis use while women showed higher rates of general psychopathology and more often displayed comorbid affective and anxiety disorders. No gender differences were found for global functioning. The results generally did not change when corrected for possible cofounders (e.g. cannabis use). However, most differences did not withstand correction for multiple testing.

Findings indicate that gender differences in symptomatology and comorbidity in ARMS are similar to those seen in overt psychosis and in healthy controls. However, observed differences are small and would only be reliably detected in studies with high statistical power. Moreover, such small effects would likely not be clinically meaningful.

An efficient indicated prevention of psychotic disorders requires valid risk criteria that work in both clinical and community samples. Yet, ultra-high risk and basic symptom criteria were recently recommended for use in clinical samples only. Their use in the community was discouraged for lack of knowledge about their prevalence, clinical relevance and risk factors in non-clinical, community settings when validly assessed with the same instruments used in the clinic.

Using semi-structured telephone interviews with established psychosis-risk instruments, we studied the prevalence of psychosis-risk symptoms and criteria, their clinical relevance (using presence of a non-psychotic mental disorder or of functional deficits as proxy measures) and their risk factors in a random, representative young adult community sample (N=2683; age 16–40 years; response rate: 63.4%).

The point-prevalence of psychosis-risk symptoms was 13.8%. As these mostly occurred too infrequent to meet frequency requirements of psychosis-risk criteria, only 2.4% of participants met psychosis-risk criteria. A stepwise relationship underlay the association of ultra-high risk and basic symptoms with proxy measures of clinical relevance, this being most significant when both occurred together. In line with models of their formation, basic symptoms were selectively associated with age, ultra-high risk symptoms with traumatic events and lifetime substance misuse.

Psychosis-risk criteria were uncommon, indicating little risk of falsely labelling individuals from the community at-risk for psychosis. Besides, both psychosis-risk symptoms and criteria seem to possess sufficient clinical relevance to warrant their broader attention in clinical practice, especially if ultra-high risk and basic symptoms occur together.

The nosology of the psychosis high-risk state is controversial. Traditionally conceived as an ‘at risk’ state for the development of psychotic disorders, it is also conceptualised as a clinical syndrome associated with functional impairment.

To investigate meta-analytically the functional status of patients at high clinical risk for psychosis and its association with longitudinal outcomes.

Three meta-analyses compared level of functioning (n = 3012) and quality of life (QoL) (n = 945) between a high-risk group, a healthy control group and group with psychosis, and baseline functioning in people in the high-risk group who did or did not have a transition to psychosis at follow-up (n = 654).

People at high risk had a large impairment in functioning (P<0.001) and worse QoL (P = 0.001) than the healthy control group, but only small to moderately better functioning (P = 0.012) and similar QoL (P = 0.958) compared with the psychosis group. Among the high-risk group, those who did not develop psychosis reported better functioning (P = 0.001) than those who did.

Our results indicate that the high-risk state is characterised by consistent and large impairments of functioning and reduction in QoL similar to those in other coded psychiatric disorders.

Decline in social functioning occurs in individuals who later develop psychosis.

To investigate whether baseline differences in disability are present in those who do and those who do not make a transition to psychosis in a group clinically at high risk and whether disability is a risk factor for transition.

Prospective multicentre, naturalistic field study with an 18-month follow-up period on 245 help-seeking individuals clinically at high risk. Disability was assessed with the Disability Assessment Schedule of the World Health Organization (WHODAS–II).

At baseline, the transition group displayed significantly greater difficulties in making new friends (z =−3.40, P = 0.001), maintaining a friendship (z =−3.00, P = 0.003), dealing with people they do not know (z =−2.28, P = 0.023) and joining community activities (z =−2.0, P = 0.05) compared with the non-transition group. In Cox regression, difficulties in getting along with people significantly contributed to the prediction of transition to psychosis in our sample (β = 0.569, s.e. = 0.184, Wald = 9.548, P = 0.002, hazard ratio (HR) = 1.767, 95% CI 1.238–2.550).

Certain domains of social disability might contribute to the prediction of psychosis in a sample clinically at high risk.

Depression is a frequent condition in early psychosis. Therefore, early detection instruments should distinguish depression from beginning psychosis

To examine whether basic symptoms, i.e. subtle subjective deficits, differ between participants suffering from a potential prodrome (n = 146), first-episode schizophrenia (n= 153) and non-psychotic depression (n = 115)

Basic symptoms were assessed with the Schizophrenia Proneness Instrument

The prodrome and schizophrenia groups did not differ in level of basic symptoms but both had higher levels than the depression group. DSM – IV depression was frequent in those suffering from a potential prodrome (38%) and first-episode schizophrenia (21%). In both groups, participants with and without depression did not differ in basic symptoms. In multivariate analyses, consideration of current depression generally facilitated correct group classification, except for participants suffering from both a potential prodrome and depression

Cognitive basic symptoms distinguished well between all three groups. However, identification of persons suffering from a potential prodrome might be enhanced by considering current affective status

Cognitive disturbances have been demonstrated in individuals with potentially prodromal symptoms in objective–neuropsychological as well as subjective-symptomatic studies. Yet, the relation between subjective and objective deficits and to different prodromal states is unclear

To explore interactions between subjective and objective cognitive measures in different prodromal states

In participants with an early (n=33) or late (n=69) initial prodromal state, cognitive subjective and objective deficits were assessed with the Schizophrenia Proneness Instrument and a comprehensive neuropsychological test battery

Participants with an early initial prodromal state were less impaired than those with a late initial state. Subjective and objective cognitive deficits were unrelated, excepttime-limited neurocognitive speed measures and subjectively reduced stress tolerance, especially in participants with an early initial prodromal state

Subjective and objective cognitive deficits are generally unrelated in the psychosis prodrome and as such they can add complementary information valuable for prediction. However, possible associations between the two levels might be better detectable in the less impaired early initial prodromal state

People in a putatively late prodromal state not only have an enhanced risk for psychosis but already suffer from mental and functional disturbances

To evaluate the acute effects of a combined supportive and antipsychotic treatment on prodromal symptoms

Putatively prodromal individuals were randomly assigned to a needs-focused intervention without (n=59) or with amisulpride (n=65). Outcome measures at 12-weeks effects were prodromal symptoms, global functioning and extrapyramidal side-effects

Amisulpride plus the needs-focused intervention produced superior effects on attenuated and full-blown psychotic symptoms, basic, depressive and negative symptoms, and global functioning. Main side-effects were prolactin associated

Coadministration of amisulpride yielded a marked symptomatic benefit. Effects require confirmation by a placebo-controlled study

The Early Detection and Intervention Programme of the German Research Network on Schizophrenia (GRNS) investigates the initial prodromal phase of psychosis in a multidimensional approach. Two intervention strategies are being studied by two large-scale multicentre projects.

To present the concept of the intervention studies, and to provide an interim report of the recruitment procedure.

Comprehensive cognitive-behavioural therapy has been developed for patients in the ‘early initial prodromal state’. For patients in the ‘late initial prodromal state’ the atypical neuroleptic amisulpride is explored. Both interventions are evaluated in randomised controlled trials using clinical management as the control condition.

Between January 2001 and March 2003, 1212 individuals seeking help for mental health problems were screened for putative prodromal symptoms at four university centres. More than 388 individuals fulfilled criteria for both interventions and 188 (48. 5%) gave informed consent to participate in the trials.

The screening procedure appears to be feasible and trial participation seems to be acceptable to a relevant proportion of people at increased risk of developing psychosis.