Psychosis superspectrum I: Nosology, etiology, and lifespan development.

This review describes the Hierarchical Taxonomy of Psychopathology (HiTOP) model of psychosis-related psychopathology, the psychosis superspectrum. The HiTOP psychosis superspectrum was developed to address shortcomings of traditional diagnoses for psychotic disorders and related conditions including low reliability, arbitrary boundaries between psychopathology and normality, high symptom co-occurrence, and heterogeneity within diagnostic categories. The psychosis superspectrum is a transdiagnostic dimensional model comprising two spectra-psychoticism and detachment-which are in turn broken down into fourteen narrow components, and two auxiliary domains-cognition and functional impairment. The structure of the spectra and their components are shown to parallel the genetic structure of psychosis and related traits. Psychoticism and detachment have distinct patterns of association with urbanicity, migrant and ethnic minority status, childhood adversity, and cannabis use. The superspectrum also provides a useful model for describing the emergence and course of psychosis, as components of the superspectrum are relatively stable over time. Changes in psychoticism predict the onset of psychosis-related psychopathology, whereas changes in detachment and cognition define later course. Implications of the superspectrum for genetic, socio-environmental, and longitudinal research are discussed. A companion review focuses on neurobiology, treatment response, and clinical utility of the superspectrum, and future research directions.

The temporal association between social isolation, distress, and psychotic experiences in individuals at clinical high-risk for psychosis.

BACKGROUND: Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis. METHODS: We used experience sampling methodology in a sample of 137 CHR participants. We analyzed the association between SI, PEs, and distress using time-lagged linear mixed-effects models. RESULTS: SI did not predict next-moment fluctuations in PEs, or vice versa. Furthermore, although SI-related distress was not predictive of subsequent PEs, general affective distress during SI was a robust predictor of next-moment PEs. CONCLUSIONS: Our results suggest that SI and PEs are not directly related on a moment-to-moment level, but a negative emotional state when alone does contribute to the risk of PEs. These findings highlight the role of affective wellbeing during early-stage psychosis development.

Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium.

Using machine learning, we recently decomposed the neuroanatomical heterogeneity of established schizophrenia to discover two volumetric subgroups-a 'lower brain volume' subgroup (SG1) and an 'higher striatal volume' subgroup (SG2) with otherwise normal brain structure. In this study, we investigated whether the MRI signatures of these subgroups were also already present at the time of the first-episode of psychosis (FEP) and whether they were related to clinical presentation and clinical remission over 1-, 3-, and 5-years. We included 572 FEP and 424 healthy controls (HC) from 4 sites (Sao Paulo, Santander, London, Melbourne) of the PHENOM consortium. Our prior MRI subgrouping models (671 participants; USA, Germany, and China) were applied to both FEP and HC. Participants were assigned into 1 of 4 categories: subgroup 1 (SG1), subgroup 2 (SG2), no subgroup membership ('None'), and mixed SG1 + SG2 subgroups ('Mixed'). Voxel-wise analyses characterized SG1 and SG2 subgroups. Supervised machine learning analyses characterized baseline and remission signatures related to SG1 and SG2 membership. The two dominant patterns of 'lower brain volume' in SG1 and 'higher striatal volume' (with otherwise normal neuromorphology) in SG2 were identified already at the first episode of psychosis. SG1 had a significantly higher proportion of FEP (32%) vs. HC (19%) than SG2 (FEP, 21%; HC, 23%). Clinical multivariate signatures separated the SG1 and SG2 subgroups (balanced accuracy = 64%; p < 0.0001), with SG2 showing higher education but also greater positive psychosis symptoms at first presentation, and an association with symptom remission at 1-year, 5-year, and when timepoints were combined. Neuromorphological subtypes of schizophrenia are already evident at illness onset, separated by distinct clinical presentations, and differentially associated with subsequent remission. These results suggest that the subgroups may be underlying risk phenotypes that could be targeted in future treatment trials and are critical to consider when interpreting neuroimaging literature.

Frontostriatothalamic effective connectivity and dopaminergic function in the psychosis continuum.

Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signalling or impaired top-down cortical regulation. We used spectral dynamic causal modelling of resting-state functional MRI to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naïve first-episode psychosis patients and 23 controls and an independent sample of 36 patients with established schizophrenia and 100 controls. We also investigated the association between FST effective connectivity and striatal 18F-DOPA uptake in an independent healthy cohort of 33 individuals who underwent concurrent functional MRI and PET. Using a posterior probability threshold of 0.95, we found that midbrain and thalamic connectivity were implicated as dysfunctional across both patient groups. Dysconnectivity in first-episode psychosis patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in established schizophrenia patients. In the healthy 18F-DOPA cohort, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits to those associated with psychotic symptom severity in patients. Overall, our findings indicate that subcortical dysconnectivity is evident in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signalling are closely related to striatal dopamine synthesis capacity, which is a robust marker for psychosis.

Influence of cannabis use on incidence of psychosis in people at clinical high risk.

AIMS: Evidence for case-control studies suggests that cannabis use is a risk factor for the development of psychosis. However, there have been limited prospective studies and the direction of this association remains controversial. The primary aim of the present study was to examine the association between cannabis use and the incidence of psychotic disorders in people at clinical high risk of psychosis. Secondary aims were to assess associations between cannabis use and the persistence of psychotic symptoms, and with functional outcome. METHODS: Current and previous cannabis use were assessed in individuals at clinical high risk of psychosis (n = 334) and healthy controls (n = 67), using a modified version of the Cannabis Experience Questionnaire. Participants were assessed at baseline and followed up for 2 years. Transition to psychosis and persistence of psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental States criteria. Level of functioning at follow up was assessed using the Global Assessment of Functioning disability scale. RESULTS: During follow up, 16.2% of the clinical high-risk sample developed psychosis. Of those who did not become psychotic, 51.4% had persistent symptoms and 48.6% were in remission. There was no significant association between any measure of cannabis use at baseline and either transition to psychosis, the persistence of symptoms, or functional outcome. CONCLUSIONS: These findings contrast with epidemiological data that suggest that cannabis use increases the risk of psychotic disorder.

The Australian Early Psychosis Collaborative Consortium (AEPCC): Improving Clinical Care in Early Psychosis.

OBJECTIVES: The field of early psychosis has undergone considerable expansion over the last few decades and has a strong evidence base of effectiveness. Like all areas of healthcare, however, early psychosis services need to more consistently deliver higher quality care to achieve better outcomes for patients and families. A national clinical research infrastructure is urgently required to enable the sector to deliver the highest quality care and expand and translate evidence more quickly and efficiently. This paper describes the establishment of the Australian Early Psychosis Collaborative Consortium (AEPCC) that aims to achieve this. CONCLUSION: AEPCC is the first of its kind in Australia (and internationally). It will deliver the required clinical research infrastructure through the implementation of a clinical quality registry, clinical trials and translation network, and lived experience network. AEPCC will provide a critical resource to better understand the state of early psychosis care, and trial new interventions on a scale that has not previously been possible in Australia.

Relationship between jumping to conclusions and clinical outcomes in people at clinical high-risk for psychosis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 association of plasma inflammatory markers with omega-3 fatty acids and their mediating role in psychotic symptoms and functioning: An analysis of the NEURAPRO clinical trial.

BACKGROUND: There is increasing evidence that dysregulation of polyunsaturated fatty acids (FAs) mediated membrane function plays a role in the pathophysiology of schizophrenia. Even though preclinical findings have supported the anti-inflammatory properties of omega-3 FAs on brain health, their biological roles as anti-inflammatory agents and their therapeutic role on clinical symptoms of psychosis risk are not well understood. In the current study, we investigated the relationship of erythrocyte omega-3 FAs with plasma immune markers in a clinical high risk for psychosis (CHR) sample. In addition, a mediation analysis was performed to examine whether previously reported associations between omega-3 FAs and clinical outcomes were mediated via plasma immune markers. Clinical outcomes for CHR participants in the NEURAPRO clinical trial were measured using the Brief Psychiatric Rating Scale (BPRS), Schedule for the Scale of Assessment of Negative Symptoms (SANS) and Social and Occupational Functioning Assessment Scale (SOFAS) scales. The erythrocyte omega-3 index [eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)] and plasma concentrations of inflammatory markers were quantified at baseline (n = 268) and 6 month follow-up (n = 146) by gas chromatography and multiplex immunoassay, respectively. In linear regression models, the baseline plasma concentrations of Interleukin (IL)-15, Intercellular adhesion molecule (ICAM)-1 and Vascular cell adhesion molecule (VCAM)-1 were negatively associated with baseline omega-3 index. In addition, 6-month change in IL-12p40 and TNF-α showed a negative association with change in omega-3 index. In longitudinal analyses, the baseline and 6 month change in omega-3 index was negatively associated with VCAM-1 and TNF-α respectively at follow-up. Mediation analyses provided little evidence for mediating effects of plasma immune markers on the relationship between omega-3 FAs and clinical outcomes (psychotic symptoms and functioning) in CHR participants. Our results indicate a predominantly anti-inflammatory relationship of omega-3 FAs on plasma inflammatory status in CHR individuals, but this did not appear to convey clinical benefits at 6 month and 12 month follow-up. Both immune and non-immune biological effects of omega-3 FAs would be resourceful in understanding the clinical benefits of omega-3 FAs in CHR papulation.

Machine learning based prediction and the influence of complement - Coagulation pathway proteins on clinical outcome: Results from the NEURAPRO trial.

BACKGROUND: Functional outcomes are important measures in the overall clinical course of psychosis and individuals at clinical high-risk (CHR), however, prediction of functional outcome remains difficult based on clinical information alone. In the first part of this study, we evaluated whether a combination of biological and clinical variables could predict future functional outcome in CHR individuals. The complement and coagulation pathways have previously been identified as being of relevance to the pathophysiology of psychosis and have been found to contribute to the prediction of clinical outcome in CHR participants. Hence, in the second part we extended the analysis to evaluate specifically the relationship of complement and coagulation proteins with psychotic symptoms and functional outcome in CHR. MATERIALS AND METHODS: We carried out plasma proteomics and measured plasma cytokine levels, and erythrocyte membrane fatty acid levels in a sub-sample (n = 158) from the NEURAPRO clinical trial at baseline and 6 months follow up. Functional outcome was measured using Social and Occupational Functional assessment Score (SOFAS) scale. Firstly, we used support vector machine learning techniques to develop predictive models for functional outcome at 12 months. Secondly, we developed linear regression models to understand the association between 6-month follow-up levels of complement and coagulation proteins with 6-month follow-up measures of positive symptoms summary (PSS) scores and functional outcome. RESULTS AND CONCLUSION: A prediction model based on clinical and biological data including the plasma proteome, erythrocyte fatty acids and cytokines, poorly predicted functional outcome at 12 months follow-up in CHR participants. In linear regression models, four complement and coagulation proteins (coagulation protein X, Complement C1r subcomponent like protein, Complement C4A & Complement C5) indicated a significant association with functional outcome; and two proteins (coagulation factor IX and complement C5) positively associated with the PSS score. Our study does not provide support for the utility of cytokines, proteomic or fatty acid data for prediction of functional outcomes in individuals at high-risk for psychosis. However, the association of complement protein levels with clinical outcome suggests a role for the complement system and the activity of its related pathway in the functional impairment and positive symptom severity of CHR patients.

Integrating trauma, self-disturbances, cognitive biases, and personality into a model for the risk of psychosis: a longitudinal study in a non-clinical sample.

The hypothesis of the psychosis continuum enables to study the mechanisms of psychosis risk not only in clinical samples but in non-clinical as well. The aim of this longitudinal study was to investigate self-disturbances (SD), a risk factor that has attracted substantial interest over the last two decades, in combination with trauma, cognitive biases and personality, and to test whether SD are associated with subclinical positive symptoms (PS) over a 12-month follow-up period. Our study was conducted in a non-clinical sample of 139 Polish young adults (81 females, age M = 25.32, SD = 4.51) who were selected for frequent experience of subclinical PS. Participants completed self-report questionnaires for the evaluation of SD (IPASE), trauma (CECA.Q), cognitive biases (DACOBS) and personality (TCI), and were interviewed for subclinical PS (CAARMS). SD and subclinical PS were re-assessed 12 months after baseline measurement. The hypothesized model for psychosis risk was tested using path analysis. The change in SD and subclinical PS over the 12-month period was investigated with non-parametric equivalent of dependent sample t-tests. The models with self-transcendence (ST) and harm avoidance (HA) as personality variables were found to be well-fitted and explained 34% of the variance in subclinical PS at follow-up. Moreover, we found a significant reduction of SD and subclinical PS after 12 months. Our study suggests that combining trauma, cognitive biases, SD and personality traits such as ST and HA into one model can enhance our understanding of appearance as well as maintenance of subclinical PS.

Basic self-disturbance trajectories in clinical high risk for psychosis: a one-year follow-up study.

Basic self-disturbance (BSD) has been proposed as a driver of symptom development in schizophrenia spectrum disorders (SSDs). In a one-year follow-up of 32 patients (15-30 years) at putative risk for psychosis, we investigated trajectories of BSD levels from baseline to follow-up, and associations between clinical characteristics at baseline and follow-up, including follow-up levels of BSD (assessed with the EASE). Clinical high risk (CHR) for psychosis status and symptom severity were assessed with the SIPS/SOPS scales and also according to the cognitive basic symptoms high-risk criteria (COGDIS). DSM-IV diagnoses, functioning and other clinical characteristics were assessed with standard clinical instruments. Higher severity of negative symptoms and meeting COGDIS criteria at baseline were associated with higher BSD levels at follow-up. All measured at follow-up, higher BSD levels correlated with higher severity of positive, negative, disorganization and general symptoms, and with a lower level of global functioning. We found higher BSD levels at follow-up in subjects with schizotypal personality disorder (SPD) at baseline (n = 5) and in SSDs at follow-up (n = 12, including nine with SPD). Mean BSD levels decreased significantly from baseline to follow-up, but individual trajectories varied considerably. Increased BSD levels were associated with higher baseline BSD levels, non-remission of positive symptoms and functional decline. Overall, the current study indicates that subgroups in the CHR population with a higher risk of non-remission or deterioration may be identified by supplementing CHR criteria with assessment of BSD and negative symptoms.

The incidence and admission rate for first-episode psychosis in young people before and during the COVID-19 pandemic in Melbourne, Australia.

OBJECTIVE: The COVID-19 pandemic has had a profound effect on global mental health, with one-third of infected individuals developing a psychiatric or neurological disorder 6 months after infection. The risk of infection and the associated restrictions introduced to reduce the spread of the virus have also impacted help-seeking behaviours. Therefore, this study aimed to determine whether there was a difference during the COVID-19 pandemic in the treated incidence of psychotic disorders and rates of admission to hospital for psychosis (including involuntary admission). METHODS: Incident cases of first-episode psychosis in young people, aged 15 to 24, at an early intervention service in Melbourne from an 8-month period before the pandemic were compared with rates during the pandemic. Hospital admission rates for these periods were also compared. RESULTS: Before the pandemic, the annual incidence of first-episode psychosis was 104.5 cases per 100,000 at-risk population, and during the pandemic it was 121.9 (incidence rate ratio = 1.14, 95% confidence interval = [0.92, 1.42], p = 0.24). Immediately after the implementation of restrictions, there was a non-significant reduction in the treated incidence (incidence rate ratio = 0.80, 95% confidence interval = [0.58, 1.09]), which was followed by a significant increase in the treated incidence in later months (incidence rate ratio = 1.94, 95% confidence interval = [1.52, 2.49]; incidence rate ratio = 1.64, 95% confidence interval = [1.25, 2.16]). Before the pandemic, 37.3% of young people with first-episode psychosis were admitted to hospital, compared to 61.7% during the pandemic (odds ratio = 2.71, 95% confidence interval = [1.73, 4.24]). Concerning the legal status of the admissions, before the pandemic, 27.3% were admitted involuntarily to hospital, compared to 42.5% during the pandemic (odds ratio = 1.97, 95% confidence interval = [1.23, 3.14]). CONCLUSION: There was a mild increase, which did not reach statistical significance, in the overall incidence of first-episode psychosis; however, the pattern of presentations changed significantly, with nearly twice as many cases presenting in the later months of the restrictions. There was a significant increase in both voluntary and involuntary admissions, and the possible explanations for these findings are discussed.

The reality of at risk mental state services: a response to recent criticisms.

BACKGROUND: In the 1990s criteria were developed to detect individuals at high and imminent risk of developing a psychotic disorder. These are known as the at risk mental state, ultra high risk or clinical high risk criteria. Individuals meeting these criteria are symptomatic and help-seeking. Services for such individuals are now found worldwide. Recently Psychological Medicine published two articles that criticise these services and suggest that they should be dismantled or restructured. One paper also provides recommendations on how ARMS services should be operate. METHODS: In this paper we draw on the existing literature in the field and present the perspective of some ARMS clinicians and researchers. RESULTS: Many of the critics' arguments are refuted. Most of the recommendations included in the Moritz et al. paper are already occurring. CONCLUSIONS: ARMS services provide management of current problems, treatment to reduce risk of onset of psychotic disorder and monitoring of mental state, including attenuated psychotic symptoms. These symptoms are associated with a range of poor outcomes. It is important to assess them and track their trajectory over time. A new approach to detection of ARMS individuals can be considered that harnesses broad youth mental health services, such as headspace in Australia, Jigsaw in Ireland and ACCESS Open Minds in Canada. Attention should also be paid to the physical health of ARMS individuals. Far from needing to be dismantled we feel that the ARMS approach has much to offer to improve the health of young people.

Investigation of structural brain correlates of neurological soft signs in individuals at ultra-high risk for psychosis.

Increased severity of neurological soft signs (NSS) in schizophrenia have been associated with abnormal brain morphology in cerebello-thalamo-cortical structures, but it is unclear whether similar structures underlie NSS prior to the onset of psychosis. The present study investigated the relationship between severity of NSS and grey matter volume (GMV) in individuals at ultra-high risk for psychosis (UHR) stratified for later conversion to psychosis. Structural T1-weighted MRI scans were obtained from 56 antipsychotic-naïve UHR individuals and 35 healthy controls (HC). The UHR individuals had follow-up data (mean follow-up: 5.2 years) to ascertain clinical outcome. Using whole-brain voxel-based morphometry, the relationship between NSS and GMV at baseline was assessed in UHR, HC, as well as individuals who later transitioned (UHR-P, n = 25) and did not transition (UHR-NP, n = 31) to psychosis. NSS total and subscale scores except motor coordination were significantly higher in UHR compared to HC. Higher signs were also found in UHR-P, but not UHR-NP. Total NSS was not associated with GMV in the whole sample or in each group. However, in UHR-P individuals, greater deficits in sensory integration was associated with lower GMV in the left cerebellum, right insula, and right middle frontal gyrus. In conclusion, NSS are present in UHR individuals, particularly those who later transitioned to a psychotic disorder. While these signs show little overall variation with GMV, the association of sensory integration deficits with lower GMV in UHR-P suggests that certain brain areas may be implicated in the development of specific neurological abnormalities in the psychosis prodrome.

The associations between migrant status and ethnicity and the identification of individuals at ultra-high risk for psychosis and transition to psychosis: a systematic review.

PURPOSE: Migrant and ethnic minority populations exhibit a higher incidence of psychotic disorders. The Ultra-High Risk for psychosis (UHR) paradigm provides an opportunity to explore the stage at which such factors influence the development of psychosis. In this systematic review, we collate and appraise the literature on the association between ethnicity and migrant status and the rate of identification of individuals at UHR, as well as their rate of transition to psychosis. METHODS: We conducted a systematic review in the Ovid Medline, PsychINFO, Pubmed, CINAHL and EMBASE databases according to PRISMA guidelines. We included studies written in English that included an UHR cohort, provided a measure of ethnicity or migrant status, and examined the incidence, rate, or risk of UHR identification or transition to psychosis. RESULTS: Of 2182 unique articles identified, seven fulfilled the criteria. One study found overrepresentation of UHR individuals from black ethnic groups, while another found underrepresentation. Two studies found increased rates of transition among certain ethnic groups and a further two found no association. Regarding migrant status, one study found that first-generation migrants were underrepresented in an UHR sample. Lastly, a lower transition rate in migrant populations was identified in one study, while two found no association. CONCLUSION: Rates of UHR identification and transition according to ethnic and migrant status were inconsistent and insufficient to conclusively explain higher incidences of psychotic disorders among these groups. We discuss the clinical implications and avenues for future research, which is required to clarify the nature of the associations.

The association between migrant status and transition in an ultra-high risk for psychosis population.

PURPOSE: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder. METHODS: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model. RESULTS: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147-756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62-1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70-1.51). CONCLUSIONS: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics.

The interplay between childhood trauma, cognitive biases, psychotic-like experiences and depression and their additive impact on predicting lifetime suicidal behavior in young adults.

BACKGROUND: Childhood trauma, psychosis risk, cognition, and depression have been identified as important risk markers for suicidal behaviors. However, little is known about the interplay between these distal and proximal markers in influencing the risk of suicide. We aim to investigate the interplay between childhood trauma, cognitive biases, psychotic-like experiences (PLEs) and depression in predicting suicidal behaviors in a non-clinical sample of young adults. METHODS: In total, 3495 young adults were recruited to an online computer-assisted web interview. We used the Prodromal Questionnaire to assess PLEs. Childhood trauma was assessed with the Traumatic Experience Checklist (three items) and Childhood Experience of Care and Abuse Questionnaire (CECA.Q, three items). Cognitive biases were assessed with a short version of the Davos Assessment of Cognitive Biases Scale. Suicidality, psychiatric diagnoses, and substance use were screened with a self-report questionnaire. RESULTS: Childhood trauma, as well as PLEs, was associated with an approximately five-fold increased risk of suicidal thoughts and plans as well as suicide attempts. Participants with depression were six times more likely to endorse suicidal behaviors. Path analysis revealed that PLEs, depression and cognitive biases are significant mediators of the relationship between trauma and suicidal behaviors. The model explained 44.6% of the variance in lifetime suicidality. CONCLUSIONS: Cognitive biases, PLEs, and depression partially mediate the relationship between childhood trauma and suicidal behaviors. The interplay between distal and proximal markers should be recognized and become part of clinical screening and therapeutic strategies for preventing risk of suicidality.

Perceptual biases and metacognition and their association with anomalous self experiences in first episode psychosis.

Anomalous self-experiences have been described as a prerequisite for anomalous perceptual experiences. Later, these anomalous perceptual experiences may then be metacognitively appraised as distressing, maintaining these experiences and later leading to anomalous (delusional) beliefs. This model of anomalous events may potentially be driven by perceptual biases and metacognitive deficits. This cross-sectional study explored the association between perceptual biases, metacognition and anomalous self- and perceptual experiences and delusional beliefs in First Episode Psychosis (FEP) and a matched healthy control sample. Fifty-eight individuals with FEP and seventy-two healthy controls were included in the main analysis. Increased auditory perceptual biases were significantly associated with increased state and trait anomalous self-experiences, in particular alienation from surroundings and emotional numbing. No significant associations were found between metacognitive efficiency and anomalous experiences. These findings may be consistent with the minimal self-disturbance model of schizophrenia spectrum vulnerability, particularly with the hyperreflexivity concept.

At-risk studies and clinical antecedents of psychosis, bipolar disorder and depression: a scoping review in the context of clinical staging.

Identifying young people at risk of developing serious mental illness and identifying predictors of onset of illness has been a focus of psychiatric prediction research, particularly in the field of psychosis. Work in this area has facilitated the adoption of the clinical staging model of early clinical phenotypes, ranging from at-risk mental states to chronic and severe mental illness. It has been a topic of debate if these staging models should be conceptualised as disorder-specific or transdiagnostic. In order to inform this debate and facilitate cross-diagnostic discourse, the present scoping review provides a broad overview of the body of literature of (a) longitudinal at-risk approaches and (b) identified antecedents of (homotypic) illness progression across three major mental disorders [psychosis, bipolar disorder (BD) and depression], and places these in the context of clinical staging. Stage 0 at-risk conceptualisations (i.e. familial high-risk approaches) were identified in all three disorders. However, formalised stage 1b conceptualisations (i.e. ultra-high-risk approaches) were only present in psychosis and marginally in BD. The presence of non-specific and overlapping antecedents in the three disorders may support a general staging model, at least in the early stages of severe psychotic or mood disorders.

Detail, dynamics and depth: useful correctives for some current research trends.

Several research trends in contemporary psychiatry would benefit from greater emphasis on detailed assessment, modelling dynamic change, and micro-level analysis. This may assist with clarifying nosological and pathoaetiological issues. We make this case by referring to three areas: psychopathology and nosology; prediction research; and 'big N' data sets.Declaration of interestNone.