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Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n = 754). Plasma proteomic data were quantified using mass spectrometry. The primary outcome was transition to psychosis over the study follow-up period. Logistic regression models were internally validated, and optimism-corrected performance metrics derived with a bootstrap procedure. In the overall sample of CHR participants (age: 18.5, SD: 3.9; 51.9% male), 20.4% (n = 154) developed psychosis within 4.4 years. The a priori-specified model showed poor risk-prediction accuracy for the development of psychosis (C-statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group level, Complement C8B, C4B, C5, and leucine-rich α-2 glycoprotein 1 (LRG1) were associated with transition to psychosis but did not surpass correction for multiple comparisons. This study did not confirm the findings from a previous proteomic prediction model of transition from CHR to psychosis. Certain complement proteins may be weakly associated with transition at a group level. Previous findings, derived from small samples, should be interpreted with caution.

Dysfunctional mental imagery is integral to the maintenance of many psychological disorders and is typically associated with stronger affective and behavioural responses than verbal cognitions. This finding extends itself to the high prevalence of suicidal mental imagery in disorders such as depression and bipolar disorder. Imagery Rescripting is a therapy approach which has been found to effectively reduce dysfunctional mental images across various mental health conditions. Thus, Imagery Rescripting of suicidal mental imagery may be effective at reducing such cognitions and ultimately associated risk. However, this remains an unexplored area within the treatment literature. This paper puts out an urgent call for clinical research to evaluate the effectiveness of such a treatment intervention, and to assist, we propose and describe a clinical approach to this to stimulate further thought and research. There are also many research questions of clinical relevance that must be explored in this field of work, which we put forward and consider in this commentary piece. What is already known about this topic: Mental imagery is a form of cognition that generates stronger emotional responses compared to verbal-linguistic thinking and is integral to the maintenance of most psychological disorders. Cognitive Behavioural Therapy (CBT) approaches are typically more effective when mental imagery techniques – such as Imagery Rescripting (ImRs) – are incorporated to target intrusive, distressing mental imagery. Mental images of suicide (comprised of both flash-back and/or flash-forward mental images) are more distressing, realistic and promote suicidal behaviours more than verbal thoughts, and are common in disorders such as depression and bipolar disorder. What this topic adds: Urgent clinical research is needed to evaluate the effectiveness of ImRs at reducing intrusive suicidal mental images, and thus related risk, and this paper proposes and describes an approach for researchers to use as a framework. There are several clinical research considerations to be made when examining ImRs of suicidal mental images, including around the delivery and safety of the intervention. More research is needed to clarify the above clinical considerations, and to further understand change mechanisms, to learn the most safe and effective ImRs approach. If ImRs is found to be effective at reducing suicidal images in upcoming clinical trials, it is strongly recommended clinicians receive adequate training and ongoing clinical supervision from an experienced practitioner given the complexities around this approach. [ABSTRACT FROM AUTHOR]

This study examined whether distress in relation to attenuated psychotic symptoms (DAPS) is associated with clinical outcomes in an ultra-high risk (UHR) for psychosis sample. We also investigated whether DAPS is associated with cognitive style (attributional style and cognitive biases) and whether amount of psychosocial treatment provided is associated with reduction in DAPS. The study was a secondary analysis of the "Neurapro" clinical trial of omega-3 fatty acids. Three hundred and four UHR patients were recruited across 10 early intervention services. Data from baseline assessment, regular assessments over 12 months, and medium term follow-up (mean = 3.4 years) were used for analysis. Findings indicated: a positive association between DAPS assessed over time and transition to psychosis; a significant positive association between baseline and longitudinal DAPS and transdiagnostic clinical and functional outcomes; a significant positive association between baseline and longitudinal DAPS and nonremission of UHR status. There was no relationship between severity of DAPS and cognitive style. A greater amount of psychosocial treatment (cognitive-behavioral case management) was associated with an increase in DAPS scores. The study indicates that UHR patients who are more distressed by their attenuated psychotic symptoms are more likely to have a poorer clinical trajectory transdiagnostically. Assessment of DAPS may therefore function as a useful marker of risk for a range of poor outcomes. The findings underline the value of repeated assessment of variables and incorporation of dynamic change into predictive modeling. More research is required into mechanisms driving distress associated with symptoms and the possible bidirectional relationship between symptom severity and associated distress. [ABSTRACT FROM AUTHOR]

Background: Neurocognitive impairments are core early features of psychosis and are observed in those at ultra‐high risk (UHR) for psychosis. The aim of the present study was to explore whether neurocognition is associated with polyunsaturated fatty acids (PUFAs), as has been observed in other clinical populations. Method: Erythrocyte levels of total omega‐3‐and omega‐6 PUFAs the omega‐3/omega‐6 ratio, were measured in 265 UHR individuals. Six domains of neurocognition as well a Composite Score, were assessed using the Brief Assessment of Cognition in Schizophrenia. Pearson's correlations were used to assess the relationship between PUFAs and neurocognition. All analyses were controlled for tobacco smoking. Results: Verbal Fluency correlated positively with eicosapentaenoic acid (P =.024) and alpha‐linolenic acid (P =.01), and negatively with docosahexanoic acid (P =.007) and Working Memory positively correlated with omega‐3/omega‐6 ratio (P =.007). Conclusions: The current results provide support for a relationship between Verbal Fluency and omega‐3 PUFAs in UHR. Further investigation is required to elucidate whether these biomarkers are useful as risk markers or in understanding the biological underpinning of neurocognitive impairment in this population. [ABSTRACT FROM AUTHOR]

Aim: Several prediction models have been introduced to identify young people at greatest risk of transitioning to psychosis. To date, none has examined the possibility of developing a clinical prediction model of outcomes other than transition. The aims of this study were to examine the association between baseline clinical predictors and outcomes including, but not limited to, transition to psychosis in young people at risk for psychosis, and to develop a prediction model for these outcomes. Methods: Several evidence‐based variables previously associated with transition to psychosis and some important clinical comorbidities experienced by ultra‐high risk (UHR) individuals were identified in 202 UHR individuals. Secondary analysis of the Neurapro clinical trial were conducted to investigate the associations between these variables and favourable (remission and recovery) or unfavourable (transition to psychosis, no remission, any recurrence and relapse) clinical outcomes. Logistic regression, best subset selection, Akaike Information Criterion and receiver operating characteristic curves were used to seek the best prediction model for clinical outcomes from all combinations of possible predictors. Results: When considered individually, only higher general psychopathology levels (P =.023) was associated with the unfavourable outcomes. Prediction models suggest that general psychopathology and functioning are predictive of unfavourable outcomes. Conclusion: The predictive performance of the resulting models was modest and further research is needed. Nonetheless, when designing early intervention centres aiming to support individuals in the early phases of a mental disorder, the proper assessment of general psychopathology and functioning should be considered in order to inform interventions and length of care provided. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: Childhood trauma (CT), abuse and neglect are commonly reported by individuals experiencing psychosis. However, there are concerns that acute psychotic symptoms, in particular delusions, may contribute to inaccurate reporting of CT. As a result, individuals experiencing psychosis may not be asked about their experiences of abuse when they are being seen in psychiatric settings. This lack of attention can directly impact on the tailoring of their clinical care. This study aimed to investigate the stability of reports of CT by young people experiencing a first psychotic episode (FEP) compared to healthy comparison subjects. Methods: Responses of 24 young people during the acute FEP and 3 months later to items on the Childhood Trauma Questionnaire (CTQ) were compared to 30 non‐psychiatric controls. All participants were aged 15 to 25 years. Results: FEP participants reported higher CT than controls at both time points. Reliability analyses (interclass correlation coefficients [ICCs]) suggested strong agreement between CT reports at baseline and follow‐up for FEP participants (.81) and controls (.91). Positive psychotic symptoms were unrelated to CT reports. Although the severity of CT reports fluctuated between assessments, complete retractions of severe abuse claims occurred rarely. Conclusions: The results suggest that retrospective self‐report can be used to reliably assess CT in young people experiencing acute psychosis. [ABSTRACT FROM AUTHOR]