Transition to psychosis rates within ultra-high risk (UHR) services have been declining. It may be possible to ‘enrich’ UHR cohorts based on the environmental characteristics seen more commonly in first-episode psychosis cohorts. This study aimed to determine whether transition rates varied according to the accumulated exposure to environmental risk factors at the individual (migrant status, asylum seeker/refugee status, indigenous population, cannabis/methamphetamine use), family (family history or parental separation), and neighborhood (population density, social deprivation, and fragmentation) level.

The study included UHR people aged 15–24 who attended the PACE clinic from 2012 to 2016. Cox proportional hazards models (frequentist and Bayesian) were used to assess the association between individual and accumulated factors and transition to psychosis. UHR status and transition was determined using the CAARMS. Benjamini–Hochberg was used to correct for multiple comparisons in frequentist analyses.

Of the 461 young people included, 55.5% were female and median follow-up was 307 days (IQR: 188–557) and 17.6% (n = 81) transitioned to a psychotic disorder. The proportion who transitioned increased incrementally according to the number of individual-level risk factors present (HR = 1.51, 95% CIs 1.19–1.93, p < 0.001, pcorr = 0.01). The number of family- and neighborhood-level exposures did not increase transition risk (p > 0.05). Cannabis use was the only specific risk factor significantly associated with transition (HR = 1.89, 95% CIs 1.22–2.93, pcorr = 0.03, BF = 6.74).

There is a dose–response relationship between exposure to individual-level psychosis-related environmental risk factors and transition risk in UHR patients. If replicated, this could be incorporated into a novel approach to identifying the highest-risk individuals within clinical services.

The ‘at-risk mental state’ (ARMS) for psychosis has been critiqued for its limited prognostic ability and identification of a limited proportion of those who will develop a first episode of psychosis (FEP). Broadening the search for high-risk groups is key to improving population-level ascertainment of psychosis risk.

To explore risk enrichment in diagnostic, demographic and socio-functional domains among individuals referred to an early intervention in psychosis (EIP) service not meeting ARMS or FEP criteria.

A retrospective file review of 16 years of referrals to a tertiary EIP service in Ireland was undertaken. Diagnostic outcomes from standardised assessments (Structured Clinical Interview for DSM), demographic (age, gender, family history, nationality) and socio-occupational (relationship status, living status, working status) variables were compiled for those not meeting criteria. These were compared with individuals diagnosed with an FEP in the same period.

From 2005 to 2021 inclusive, of 2025 index assessments, 27.6% (n = 558) did not meet either FEP or ARMS criteria, which is notably higher than the 5.4% (n = 110) meeting ARMS criteria. This group had high psychiatric morbidity, with 65.4% meeting criteria for at least one DSM Axis I disorder. Depressive, anxiety and substance use disorders predominated. Their functional markers were poor, and comparable to the FEP cohort.

This group is enriched for psychosis risk factors. They are a larger group than those meeting ARMS criteria, a finding that may reflect EIP service configuration. They may be an important focus for further study in the search for at-risk populations beyond the current ARMS model.

Hippocampal hyperperfusion has been observed in people at Clinical High Risk for Psychosis (CHR), is associated with adverse longitudinal outcomes and represents a potential treatment target for novel pharmacotherapies. Whether cannabidiol (CBD) has ameliorative effects on hippocampal blood flow (rCBF) in CHR patients remains unknown.

Using a double-blind, parallel-group design, 33 CHR patients were randomized to a single oral 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labeling. We examined differences relating to CHR status (controls v. placebo), effects of CBD in CHR (placebo v. CBD) and linear between-group relationships, such that placebo > CBD > controls or controls > CBD > placebo, using a combination of hypothesis-driven and exploratory wholebrain analyses.

Placebo-treated patients had significantly higher hippocampal rCBF bilaterally (all pFWE<0.01) compared to healthy controls. There were no suprathreshold effects in the CBD v. placebo contrast. However, we found a significant linear relationship in the right hippocampus (pFWE = 0.035) such that rCBF was highest in the placebo group, lowest in controls and intermediate in the CBD group. Exploratory wholebrain results replicated previous findings of hyperperfusion in the hippocampus, striatum and midbrain in CHR patients, and provided novel evidence of increased rCBF in inferior-temporal and lateral-occipital regions in patients under CBD compared to placebo.

These findings suggest that hippocampal blood flow is elevated in the CHR state and may be partially normalized by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population.

Childhood trauma is associated with an elevated risk for psychosis, but the psychological mechanisms involved remain largely unclear. This study aimed to investigate emotional and psychotic stress reactivity in daily life as a putative mechanism linking childhood trauma and clinical outcomes in individuals at ultra-high-risk (UHR) for psychosis.

Experience sampling methodology was used to measure momentary stress, affect and psychotic experiences in the daily life of N = 79 UHR individuals in the EU-GEI High Risk Study. The Childhood Trauma Questionnaire was used to assess self-reported childhood trauma. Clinical outcomes were assessed at baseline, 1- and 2-year follow-up.

The association of stress with positive (β = −0.14, p = 0.010) and negative affect (β = 0.11, p = 0.020) was modified by transition status such that stress reactivity was greater in individuals who transitioned to psychosis. Moreover, the association of stress with negative affect (β = 0.06, p = 0.019) and psychotic experiences (β = 0.05, p = 0.037) was greater in individuals exposed to high v. low levels of childhood trauma. We also found evidence that decreased positive affect in response to stress was associated with reduced functioning at 1-year follow-up (B = 6.29, p = 0.034). In addition, there was evidence that the association of childhood trauma with poor functional outcomes was mediated by stress reactivity (e.g. indirect effect: B = −2.13, p = 0.026), but no evidence that stress reactivity mediated the association between childhood trauma and transition (e.g. indirect effect: B = 0.14, p = 0.506).

Emotional and psychotic stress reactivity may be potential mechanisms linking childhood trauma with clinical outcomes in UHR individuals.

Psychotic experiences may emerge in more severe cases of common mental disorders (CMD). Previous work identified that 30% of patients treated by mental health services in primary healthcare, specifically the Improving Access to Psychological Therapies (IAPT) programme in England, reported psychotic experiences, began treatment with more severe CMD and were less likely to reach recovery.

To replicate our previous assessment of psychotic experiences in the IAPT programme using a more sensitive threshold and determine its impact on the prevalence of psychotic experience and likelihood of recovery. Additionally, to compare recovery rates between patients with and without psychotic experiences at the end of therapy.

The Community Assessment of Psychic Experiences (CAPE-P15) with a cut-off of 1.30 was used to determine the prevalence of psychotic experiences. Recovery rates were determined using measures collected in the IAPT programme for depression (PHQ-9) and anxiety (GAD-7). Multi-group growth models estimated improvement trajectories.

In total, 2042 patients with CMD completed the CAPE-P15. The mean age was 39.8. The prevalence of psychotic experiences was 18% higher when using a lower threshold. The recovery rate for patients with psychotic experiences was lower (36%) than for those without (64%). Despite sharing similar improvement trajectories, the higher initial severity of CMD among patients with psychotic experiences impeded likelihood of recovery.

As psychotic experiences may be a marker of severity in CMD, the benefits of identifying these in IAPT populations may also apply to patients with milder experiences. Further investigation of the consequential demands on service provision and how this would affect clinical practice is recommended.

Impairments in self-recognition (i.e. recognition of own thoughts and actions) have been repeatedly shown in individuals with schizophrenia. According to classical clinical characterizations, schizophrenia is included in a continuum encompassing a large range of genetic statuses, psychotic states and symptoms. The current meta-analysis aims to determine whether self-recognition is affected by individuals within the psychosis continuum.

Three populations were considered: people with an at-risk mental state for psychosis (ARMS), hallucination-prone individuals and unaffected relatives of patients with schizophrenia. Eleven studies contrasted self-recognition between these three populations (n = 386) and healthy controls (n = 315) and four studies used correlational analysis to estimate comparable effects (n = 629). Eligible studies used experimental paradigms including source-monitoring and self-monitoring.

We observed significantly reduced self-recognition accuracy in these populations [g = −0.44 (−0.71 to −0.17), p = 0.002] compared to controls. No influence of the type of population, experimental paradigm or study design was observed.

The present analysis argues for self-recognition deficits in populations with no full-blown psychotic symptoms represented across the continuum of psychosis.

Although hallucinations have been studied in terms of prevalence and its associations with psychopathology and functional impairment, very little is known about sensory modalities other than auditory (i.e. haptic, visual and olfactory), as well the incidence of hallucinations, factors predicting incidence and subsequent course.

We examined the incidence, course and risk factors of hallucinatory experiences across different modalities in two unique prospective general population cohorts in the same country using similar methodology and with three interview waves, one over the period 1996–1999 (NEMESIS) and one over the period 2007–2015 (NEMESIS-2).

In NEMESIS-2, the yearly incidence of self-reported visual hallucinations was highest (0.33%), followed by haptic hallucinations (0.31%), auditory hallucinations (0.26%) and olfactory hallucinations (0.23%). Rates in NEMESIS-1 were similar (respectively: 0.35%, 0.26%, 0.23%, 0.22%). The incidence of clinician-confirmed hallucinations was approximately 60% of the self-reported rate. The persistence rate of incident hallucinations was around 20–30%, increasing to 40–50% for prevalent hallucinations. Incident hallucinations in one modality were very strongly associated with occurrence in another modality (median OR = 59) and all modalities were strongly associated with delusional ideation (median OR = 21). Modalities were approximately equally strongly associated with the presence of any mental disorder (median OR = 4), functioning, indicators of help-seeking and established environmental risk factors for psychotic disorder.

Hallucinations across different modalities are a clinically relevant feature of non-psychotic disorders and need to be studied in relation to each other and in relation to delusional ideation, as all appear to have a common underlying mechanism.

Few studies have followed up patients with a clinical high risk (CHR) for psychosis for more than 2–3 years. We aimed to investigate the rates and baseline predictors for remission from CHR and transition to psychosis over a follow-up period of up to 16 years. Additionally, we examined the clinical and functional long-term outcome of CHR patients who did not transition.

We analyzed the long-term course of CHR patients that had been included in the longitudinal studies “Früherkennung von Psychosen” (FePsy) or “Bruderholz” (BHS). Those patients who had not transitioned to psychosis during the initial follow-up periods (2/5 years), were invited for additional follow-ups.

Originally, 255 CHR patients had been included. Of these, 47 had transitioned to psychosis during the initial follow-ups. Thus, 208 were contacted for the long-term follow-up, of which 72 (34.6%) participated. From the original sample of 255, 26%, 31%, 35%, and 38% were estimated to have transitioned after 3, 5, 10, and 16 years, respectively, and 51% had remitted from their high risk status at the latest follow-up. Better psychosocial functioning at baseline was associated with a higher rate of remission. Of the 72 CHR patients re-assessed at long-term follow-up, 60 had not transitioned, but only 28% of those were fully recovered clinically and functionally.

Our study shows the need for follow-ups and clinical attention longer than the usual 2–3 years as there are several CHR patients with later transitions and only a minority of CHR those without transition fully recovers.

Cognitive impairment is a core feature of schizophrenia and has been observed in both familial (FHR) and clinical high-risk (CHR) samples. Nonetheless, there is a paucity of research directly contrasting cognitive profiles in these two high-risk states and first-episode schizophrenia. This study aimed to compare cognitive functions in patients with first-episode schizophrenia-spectrum disorder (FES), their unaffected siblings (FHR), CHR individuals and healthy controls.

A standardized battery of cognitive assessments was administered to 69 FES patients, 71 help-seeking CHR individuals without family history of psychotic disorder, 50 FHR participants and 68 controls. FES and CHR participants were recruited from territory-wide early intervention service for psychosis in Hong Kong. CHR status was ascertained using Comprehensive Assessment of At-Risk Mental State.

Among four groups, FES patients displayed the largest global cognitive impairment and had medium-to-large deficits across all cognitive tests relative to controls. CHR and FHR participants significantly underperformed in most cognitive tests than controls. Among various cognitive tests, digit symbol coding demonstrated the greatest magnitude of impairment in FES and CHR groups compared with controls. No significant difference between two high-risk groups was observed in global cognition and all individual cognitive tests except digit symbol coding which showed greater deficits in CHR than in FHR participants.

Clinical and familial risk groups experienced largely comparable cognitive impairment that was intermediate between FES and controls. Digit symbol coding may have the greatest discriminant capacity in distinguishing FES and CHR from healthy controls, and between two high-risk samples.

Patients with psychosis display the so-called ‘Jumping to Conclusions’ bias (JTC) – a tendency for hasty decision-making in probabilistic reasoning tasks. So far, only a few studies have evaluated the JTC bias in ‘at-risk mental state’ (ARMS) patients, specifically in ARMS samples fulfilling ‘ultra-high risk’ (UHR) criteria, thus not allowing for comparisons between different ARMS subgroups.

In the framework of the PREVENT (secondary prevention of schizophrenia) study, a JTC task was applied to 188 patients either fulfilling UHR criteria or presenting with cognitive basic symptoms (BS). Similar data were available for 30 healthy control participants matched for age, gender, education and premorbid verbal intelligence. ARMS patients were identified by the Structured Interview for Prodromal Symptoms (SIPS) and the Schizophrenia Proneness Instrument – Adult Version (SPI-A).

The mean number of draws to decision (DTD) significantly differed between ARM -subgroups: UHR patients made significantly less draws to make a decision than ARMS patients with only cognitive BS. Furthermore, UHR patients tended to fulfil behavioural criteria for JTC more often than BS patients. In a secondary analysis, ARMS patients were much hastier in their decision-making than controls. In patients, DTD was moderately associated with positive and negative symptoms as well as disorganization and excitement.

Our data indicate an enhanced JTC bias in the UHR group compared to ARMS patients with only cognitive BS. This underscores the importance of reasoning deficits within cognitive theories of the developing psychosis. Interactions with the liability to psychotic transitions and therapeutic interventions should be unravelled in longitudinal studies.

Metamemory describes the monitoring and knowledge about one's memory capabilities. Patients with schizophrenia have been found to be less able in differentiating between correct and false answers (smaller confidence gap) when asked to provide retrospective confidence ratings in previous studies. Furthermore, higher proportions of very-high-confident but false responses have been found in this patient group (high knowledge corruption). Whether and how these biases contribute to the early pathogenesis of psychosis is yet unclear. This study thus aimed at investigating metamemory function in the early course of psychosis.

Patients in an at-risk mental state for psychosis (ARMS, n = 34), patients with a first episode of psychosis (FEP, n = 21) and healthy controls (HCs, n = 38) were compared on a verbal recognition task combined with retrospective confidence-level ratings.

FEP patients showed the smallest confidence gap, followed by ARMS patients, followed by HCs. All groups differed significantly from each other. Regarding knowledge corruption, FEP patients differed significantly from HCs, whereas a statistical trend was revealed in comparison of ARMS and FEP groups. Correlations were revealed between metamemory, measures of positive symptoms and working memory performance.

These data underline the presence of a metamemory bias in ARMS patients which is even more pronounced in FEP patients. The bias might represent an early cognitive marker of the beginning psychotic state. Longitudinal studies are needed to unravel whether metacognitive deficits predict the transition to psychosis and to evaluate therapeutic interventions.

Individuals identified as at ultra-high risk (UHR) for psychosis are at risk of poor functional outcome regardless of development of psychotic disorder. Studies examining longitudinal predictors of poor functioning have tended to be small and report only medium-term follow-up data. We sought to examine clinical predictors of functional outcome in a long-term longitudinal study.

Participants were 268 (152 females, 116 males) individuals identified as UHR 2–14 years previously. A range of clinical and sociodemographic variables were assessed at baseline. Functioning at follow-up was assessed using the Social and Occupational Functioning Assessment Scale (SOFAS).

Baseline negative symptoms, impaired emotional functioning, disorders of thought content, low functioning, past substance use disorder and history of childhood maltreatment predicted poor functioning at follow-up in univariate analyses. Only childhood maltreatment remained significant in the multivariate analysis (p < 0.001). Transition to psychosis was also significantly associated with poor functioning at long-term follow-up [mean SOFAS score 59.12 (s.d. = 18.54) in the transitioned group compared to 70.89 (s.d. = 14.00) in the non-transitioned group, p < 0.001]. Childhood maltreatment was a significant predictor of poor functioning in both the transitioned and non-transitioned groups.

Childhood maltreatment and transition to psychotic disorder independently predicted poor long-term functioning. This suggests that it is important to assess history of childhood maltreatment in clinical management of UHR individuals. The finding that transition to psychosis predicts poor long-term functioning strengthens the evidence that the UHR criteria detect a subgroup at risk for schizophrenia.

Clinical equipoise regarding preventative treatments for psychosis has encouraged the development and evaluation of psychosocial treatments, such as cognitive behavioural therapy (CBT).

A systematic review and meta-analysis was conducted, examining the evidence for the effectiveness of CBT-informed treatment for preventing psychosis in people who are not taking antipsychotic medication, when compared to usual or non-specific control treatment. Included studies had to meet basic quality criteria, such as concealed and random allocation to treatment groups.

Our search produced 1940 titles, out of which we found seven completed trials (six published). The relative risk (RR) of developing psychosis was reduced by more than 50% for those receiving CBT at every time point [RR at 6 months 0.47, 95% confidence interval (CI) 0.27–0.82, p = 0.008 (fixed-effects only: six randomized controlled trials (RCTs), n = 800); RR at 12 months 0.45, 95% CI 0.28–0.73, p = 0.001 (six RCTs, n = 800); RR at 18–24 months 0.41, 95% CI 0.23–0.72, p = 0.002 (four RCTs, n = 452)]. Heterogeneity was low in every analysis and the results were largely robust to the risk of an unpublished 12-month study having unfavourable results. CBT was also associated with reduced subthreshold symptoms at 12 months, but not at 6 or 18–24 months. No effects on functioning, symptom-related distress or quality of life were observed. CBT was not associated with increased rates of clinical depression or social anxiety (two studies).

CBT-informed treatment is associated with a reduced risk of transition to psychosis at 6, 12 and 18–24 months, and reduced symptoms at 12 months. Methodological limitations and recommendations for trial reporting are discussed.

Many research groups have attempted to predict which individuals with an at-risk mental state (ARMS) for psychosis will later develop a psychotic disorder. However, it is difficult to predict the course and outcome based on individual symptoms scores.

Data from 318 ARMS individuals from two specialized services for ARMS subjects were analysed using latent class cluster analysis (LCCA). The score on the Comprehensive Assessment of At-Risk Mental States (CAARMS) was used to explore the number, size and symptom profiles of latent classes.

LCCA produced four high-risk classes, censored after 2 years of follow-up: class 1 (mild) had the lowest transition risk (4.9%). Subjects in this group had the lowest scores on all the CAARMS items, they were younger, more likely to be students and had the highest Global Assessment of Functioning (GAF) score. Subjects in class 2 (moderate) had a transition risk of 10.9%, scored moderately on all CAARMS items and were more likely to be in employment. Those in class 3 (moderate–severe) had a transition risk of 11.4% and scored moderately severe on the CAARMS. Subjects in class 4 (severe) had the highest transition risk (41.2%), they scored highest on the CAARMS, had the lowest GAF score and were more likely to be unemployed. Overall, class 4 was best distinguished from the other classes on the alogia, avolition/apathy, anhedonia, social isolation and impaired role functioning.

The different classes of symptoms were associated with significant differences in the risk of transition at 2 years of follow-up. Symptomatic clustering predicts prognosis better than individual symptoms.