Risk State For Psychosis Research Articles

A systematic review and meta-analysis of neuroimaging studies examining synaptic density in individuals with psychotic spectrum disorders

BackgroundPsychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology. We conducted a systematic review of the literature to identify neuroimaging studies specifically examining synaptic density across the psychosis spectrum.MethodsPRISMA guidelines on reporting were followed. We systematically searched MEDLINE, Embase, APA PsycINFO, Web of Science and The Cochrane Library from inception to December 8, 2023, and included all original peer-reviewed articles or completed clinical neuroimaging studies of any modality measuring synaptic density in participants with a diagnosis of psychosis spectrum disorder as well as individuals with psychosis-risk states. The NIH quality assessment tool for observational cohort and cross-sectional studies was used for the risk of bias assessment.ResultsFive studies (k = 5) met inclusion criteria, comprising n = 128 adults (psychotic disorder; n = 61 and healthy volunteers; n = 67 and specifically measuring synaptic density via positron emission tomography (PET) imaging of the synaptic vesicle glycoprotein 2 A (SV2A). Three studies were included in our primary meta-analysis sharing the same outcome measure of SV2A binding, volume of distribution (VT). Regional SV2A VT was reduced in psychotic disorder participants in comparison to healthy volunteers, including the occipital lobe (Mean Difference (MD)= -2.17; 95% CI: -3.36 to -0.98; P < 0.001 ), temporal lobe (MD: -2.03; 95% CI: -3.19 to -0.88; P < 0.001 ), parietal lobe (MD:-1.61; 95% CI: -2.85 to -0.37; P = 0.01), anterior cingulate cortex (MD= -1.47; 95% CI: -2.45 to -0.49; P = 0.003), frontal cortex (MD: -1.16; 95% CI: -2.18 to -0.15; P = 0.02), amygdala (MD: -1.36; 95% CI: -2.20 to -0.52, p = 0.002), thalamus (MD:-1.46; 95% CI:-2.46 to -0.46, p = 0.004) and hippocampus (MD= -0.96; 95% CI: -1.59 to -0.33; P = 0.003).ConclusionsPreliminary studies provide in vivo evidence for reduced synaptic density in psychotic disorders. However, replication of findings in larger samples is required prior to definitive conclusions being drawn.PROSPEROCRD42022359018.

Multipronged investigation of morphometry and connectivity of hippocampal network in relation to risk for psychosis using ultrahigh field MRI.

Hippocampal abnormalities are associated with psychosis-risk states. Given the complexity of hippocampal anatomy, we conducted a multipronged examination of morphometry of regions connected with hippocampus, and structural covariance network (SCN) and diffusion-weighted circuitry among 27 familial high-risk (FHR) individuals who were past the highest risk for conversion to psychoses and 41 healthy controls using ultrahigh-field high-resolution 7 Tesla (7T) structural and diffusion MRI data. We obtained fractional anisotropy and diffusion streams of white matter connections and examined correspondence of diffusion streams with SCN edges. Nearly 89 % of the FHR group had an axis-I disorder including 5 with schizophrenia. Therefore, we compared the entire FHR group regardless of the diagnosis (All_FHR=27) and FHR-without-schizophrenia (n=22) with 41 controls in this integrative multimodal analysis. We found striking volume loss in bilateral hippocampus, particularly the head, bilateral thalamus, caudate, and prefrontal regions. All_FHR and FHR-without-SZ SCNs showed significantly lower assortativity and transitivity but higher diameter compared to controls, but FHR-without-SZ SCN differed on every graph metric compared to All_FHR suggesting disarrayed network with no hippocampal hubs. Fractional anisotropy and diffusion streams were lower in FHR suggesting white matter network impairment. White matter edges showed significantly higher correspondence with SCN edges in FHR compared to controls. These differences correlated with psychopathology and cognitive measures. Our data suggest that hippocampus may be a "neural hub" contributing to psychosis risk. Higher correspondence of white matter tracts with SCN edges suggest that shared volume loss may be more coordinated among regions within the hippocampal white matter circuitry.

Activation of Internal Correctness Monitoring Circuitry in Youths With Psychosis Spectrum Symptoms

BackgroundSelf-directed performance monitoring is a critical contributor to cognitive performance and general functioning and is impacted by psychiatric symptoms and personality traits, but has been understudied in psychosis-risk states. We have shown that ventral striatum (VS) responds to correctness during cognitive tasks where no explicit feedback is required, and this intrinsic reinforcement response is reduced in schizophrenia. MethodsHere, we examined this phenomenon in youths (n = 796, age range 11–22 years) from the Philadelphia Neurodevelopmental Cohort (PNC) performing a working memory functional magnetic resonance imaging task. We hypothesized that VS would respond to internal correctness monitoring, while classic salience network regions, such as dorsal anterior cingulate cortex and anterior insular cortex, would reflect internal error monitoring and that these responses would increase with age. We expected that neurobehavioral measures of performance monitoring would be reduced in youths with subclinical psychosis spectrum features and would correlate with amotivation severity. ResultsSupporting these hypotheses, we found correct>incorrect activation in VS and incorrect>correct activation in anterior cingulate cortex and anterior insular cortex. Furthermore, VS activation was positively correlated with age, reduced in youths with psychosis spectrum features, and inversely correlated with amotivation. However, these patterns were not significant in anterior cingulate cortex and anterior insular cortex. ConclusionsThese findings advance our understanding of the neural underpinnings of performance monitoring and its impairment in adolescents with psychosis spectrum features. Such understanding can facilitate investigation of the developmental trajectory of normative and aberrant performance monitoring; contribute to early identification of youths at elevated risk for poor academic, occupational, or psychiatric outcomes; and provide potential targets for therapeutic development.

Thalamocortical dysrhythmia in patients with schizophrenia spectrum disorder and individuals at clinical high risk for psychosis.

Thalamocortical dysrhythmia (TCD) is a model characterized by abnormal resting-state thalamic oscillatory patterns where the alpha rhythm is replaced by cross-frequency coupling of low- and high-frequency rhythms. Although disrupted thalamic function is a suggested important pathophysiological mechanism underlying schizophrenia, knowledge regarding the TCD model in schizophrenia spectrum disorder (SSD) patients and individuals at clinical high risk (CHR) for psychosis is limited. A total of 169 SSD patients, 106 individuals at CHR for psychosis, and 105 healthy controls (HCs) underwent resting-state electroencephalography recordings. We performed mean global field power (MGFP) spectral analysis between 1 and 49 Hz as well as source-level theta phase-gamma amplitude coupling (TGC) analysis and compared resting-state oscillatory patterns across groups. Correlations between altered TGC values and psychotic symptom severity in the patient group were investigated. Spectral MGFP of low- and high-frequencies was larger in the SSD and CHR groups than in the HC group. The TGC of SSD patients was greater than that of HCs in the right frontal, right parietal, and left and right limbic lobes. Greater TGC in the right frontal and limbic lobes was associated with positive symptom severity in SSD patients. However, TGC in the CHR group was comparable to that in the HCs and was smaller than that in the SSD group in widespread cortical regions. The TCD pattern may be apparent after frank psychotic disorder onset in tandem with overt positive symptoms. A psychosis-risk state without overt psychotic symptoms could be characterized by abnormally increased low- and high-frequency activities with relatively preserved TGC.

W73. SUPPRESSION OF THE INFLAMMATORY RESPONSE IN SCHIZOPHRENIA HIPSC-DERIVED NEURAL PROGENITORS: A GENE-ENVIRONMENT INTERACTION STUDY

Cognitive deficits are typically seen in schizophrenia and in the prodrome, and are a major predictor of functional outcomes in patients. In Africa, few studies have investigated neurocognition in psychosis, which presents a gap in our understanding of the heterogeneity of the illness. In this study, we assessed neurocognition among the largest sample of psychosis-risk participants recruited in the continent to date.The study was conducted in Kenya, and involved 295 psychiatric medication-naïve participants at clinical high-risk (CHR) for psychosis and healthy controls, aged 15–25 yrs. Psychosis-risk status was determined separately using the Structured Interview of Psychosis-Risk Syndromes (i.e. CHR) and by self-report with the Washington Early Recognition Center Affectivity and Psychosis Screen. Eleven tests were administered using the University of Pennsylvania Computerized Neurocognitive Battery. Test performance across groups were investigated, as well as demographic and clinical effects.Fewer participants were designated as being at psychosis-risk with structured interview (n = 47; CHR) than with self-report (n = 155). A MANOVA of cognitive test performance was significant only when groups were ascertained based on self-report (p = 0.03), with decreased performance in the risk group on verbal intelligence (p = 0.003; d = 0.39), emotion recognition (p = 0.003; d = 0.36), sensorimotor processing (p = 0.01; d = 0.31) and verbal memory (p = 0.035; d = 0.21). Only verbal intelligence was significantly worse in the CHR group compared to controls (p = 0.036; d = 0.45). There were no significant age and gender relationships.Deficits across multiple cognitive domains are present in Kenyan psychosis-risk youth, most significantly in verbal intelligence. The pattern of cognitive deficits and an absence of gender effects may represent ethnicity-specific phenotypes of the psychosis-risk state. Longitudinal studies of neurocognition in Kenyan patients who convert to psychosis may enhance risk prediction in this population, and facilitate targeted interventions.

Anomalous self-experiences (ASE) in relation to clinical high risk for psychosis (CHR[sbnd]P), childhood trauma and general psychopathology among adolescent and young adult help seekers

BackgroundAnomalous self-experiences (ASE) are suggested as a phenotypic core feature of schizophrenia spectrum disorders and present in at risk samples as well. In our study, we investigated the relation between ASE and clinical high risk state for psychosis (CHRP) against the background of further influencing factors like childhood trauma and general psychopathology. Methods126 help-seeking adolescents were included. CHR-P patients were identified using the Structured Interview for Psychosis-Risk Syndromes (SIPS). ASE were assessed with the Inventory of Psychotic-like Anomalous Self-Experiences (IPASE). Childhood trauma, depression and anxiety were assessed with well-established questionnaires (CTQ; PHQ-9; GAD-7). ResultsCHR-P subgroup (n = 50, 39.7%) show significantly higher scores in IPASE total (t (81.07) = -5.150, p = .000) and CTQ total (t (85.95) = -2.75, p = .007) in comparison with the non CHR-P subgroup. Logistic regression analysis confirmed that IPASE total could predict CHR-P status (OR 1.03, 95% CI 1.01-1.04, p = .000). Furthermore, CTQ total and IPASE total show moderate to strong positive correlation (r = 0.44, p < .001) as well as CTQ total with both IPASE subdomains Cognition (r = 0.404, p < .001) and Self- Awareness (r = 0.443, p < .001). ConclusionThe CHR-P subgroup shows significantly more ASE than the non CHR-P subgroup. Further, ASE predicted CHR-P status. Our results indicated that ASE could play a considerable role in the identification of high risk for developing schizophrenia spectrum disorder and could complement CHR-P testing. Importantly, it seems that ASE may be related to exposure to childhood trauma.

Risk and protective factors for mental disorders beyond genetics: an evidence-based atlas.

Decades of research have revealed numerous risk factors for mental disorders beyond genetics, but their consistency and magnitude remainuncer-tain. We conducted a "meta-umbrella" systematic synthesis of umbrella reviews, which are systematic reviews of meta-analyses of individual studies, by searching international databases from inception to January 1, 2021. We included umbrella reviews on non-purely genetic risk or protective factors for any ICD/DSM mental disorders, applying an established classification of the credibility of the evidence: class I (convincing), class II (highly suggestive), class III (suggestive), class IV (weak). Sensitivity analyses were conducted on prospective studies to test for temporality (reverse causation), TRANSD criteria were applied to test transdiagnosticity of factors, and A Measurement Tool to Assess Systematic Reviews (AMSTAR) was employed to address the quality of meta-analyses. Fourteen eligible umbrella reviews were retrieved, summarizing 390 meta-analyses and 1,180 associations between putative risk or protective factors and mental disorders. We included 176 class I to III evidence associations, relating to 142 risk/protective factors. The most robust risk factors (class I or II, from prospective designs) were 21. For dementia, they included type 2 diabetes mellitus (risk ratio, RR from 1.54 to 2.28), depression (RR from 1.65 to 1.99) and low frequency of social contacts (RR=1.57). For opioid use disorders, the most robust risk factor was tobacco smoking (odds ratio, OR=3.07). For non-organic psychotic disorders, the most robust risk factors were clinical high risk state for psychosis (OR=9.32), cannabis use (OR=3.90), and childhood adversities (OR=2.80). For depressive disorders, they were widowhood (RR=5.59), sexual dysfunction (OR=2.71), three (OR=1.99) or four-five (OR=2.06) metabolic factors, childhood physical (OR=1.98) and sexual (OR=2.42) abuse, job strain (OR=1.77), obesity (OR=1.35), and sleep disturbances (RR=1.92). For autism spectrum disorder, the most robust risk factor was maternal overweight pre/during pregnancy (RR=1.28). For attention-deficit/hyperactivity disorder (ADHD), they were maternal pre-pregnancy obesity (OR=1.63), maternal smoking during pregnancy (OR=1.60), and maternal overweight pre/during pregnancy (OR=1.28). Only one robust protective factor was detected: high physical activity (hazard ratio, HR=0.62) for Alzheimer's disease. In all, 32.9% of the associations were of high quality, 48.9% of medium quality, and 18.2% of low quality. Transdiagnostic class I-III risk/protective factors were mostly involved in the early neurodevelopmental period. The evidence-based atlas of key risk and protective factors identified in this study represents a benchmark for advancing clinical characterization and research, and for expanding early intervention and preventive strategies for mental disorders.

Neurocognition in Kenyan youth at clinical high risk for psychosis

IntroductionCognitive deficits are typically seen in schizophrenia and in the prodrome, and are a major predictor of functional outcomes in patients. In Africa, few studies have investigated neurocognition in psychosis, which presents a gap in our understanding of the heterogeneity of the illness. In this study, we assessed neurocognition among the largest sample of psychosis-risk participants recruited in the continent to date. MethodsThe study was conducted in Kenya, and involved 295 psychiatric medication-naïve participants at clinical high-risk (CHR) for psychosis and healthy controls, aged 15–25 yrs. Psychosis-risk status was determined separately using the Structured Interview of Psychosis-Risk Syndromes (i.e. CHR) and by self-report with the Washington Early Recognition Center Affectivity and Psychosis Screen. Eleven tests were administered using the University of Pennsylvania Computerized Neurocognitive Battery. Test performance across groups were investigated, as well as demographic and clinical effects. ResultsFewer participants were designated as being at psychosis-risk with structured interview (n = 47; CHR) than with self-report (n = 155). A MANOVA of cognitive test performance was significant only when groups were ascertained based on self-report (p = 0.03), with decreased performance in the risk group on verbal intelligence (p = 0.003; d = 0.39), emotion recognition (p = 0.003; d = 0.36), sensorimotor processing (p = 0.01; d = 0.31) and verbal memory (p = 0.035; d = 0.21). Only verbal intelligence was significantly worse in the CHR group compared to controls (p = 0.036; d = 0.45). There were no significant age and gender relationships. ConclusionDeficits across multiple cognitive domains are present in Kenyan psychosis-risk youth, most significantly in verbal intelligence. The pattern of cognitive deficits and an absence of gender effects may represent ethnicity-specific phenotypes of the psychosis-risk state. Longitudinal studies of neurocognition in Kenyan patients who convert to psychosis may enhance risk prediction in this population, and facilitate targeted interventions.

Salience Signaling in Psychosis Risk States: Amygdala and Insula Abnormalities in Association With Illness Severity

Aberrant reward processing may underlie initial symptom formation in psychosis, but few studies have examined the neural bases of reward prediction error signaling in individuals at clinical high-risk (CHR) for the disorder. As the amygdala and anterior insula (AI) are implicated in emotion and salience signaling in psychosis, studies are warranted in youth at CHR.

Double Trouble at the Hippocampal Networks in Psychosis Risk States: A Multi-Pronged Morphometric-Mathematical Study Using Ultra-High Field MRI Data

Hippocampal abnormalities are widely reported in schizophrenia and psychosis-risk states. Given the complexity of hippocampal structure/function, we conducted a more granular examination of intrinsic (the trisynaptic circuit comprising dentate gyrus, CA1 and CA3) and extrinsic circuitry, and hippocampal shape using ultra-high-field high-resolution MRI (7T) on 18 familial high-risk (FHR) (age=30.83±3.85 years) and 35 control (age=28.25±3.91 years) subjects.

What makes the psychosis 'clinical high risk' state risky: psychosis itself or the co-presence of a non-psychotic disorder?

Although attenuated psychotic symptoms in the psychosis clinical high-risk state (CHR-P) almost always occur in the context of a non-psychotic disorder (NPD), NPD is considered an undesired 'comorbidity' epiphenomenon rather than an integral part of CHR-P itself. Prospective work, however, indicates that much more of the clinical psychosis incidence is attributable to prior mood and drug use disorders than to psychosis clinical high-risk states per se. In order to examine this conundrum, we analysed to what degree the 'risk' in CHR-P is indexed by co-present NPD rather than attenuated psychosis per se. We examined the incidence of early psychotic experiences (PE) with and without NPD (mood disorders, anxiety disorders, alcohol/drug use disorders), in a prospective general population cohort (n = 6123 at risk of incident PE at baseline). Four interview waves were conducted between 2007 and 2018 (NEMESIS-2). The incidence of PE, alone (PE-only) or with NPD (PE + NPD) was calculated, as were differential associations with schizophrenia polygenic risk score (PRS-Sz), environmental, demographical, clinical and cognitive factors. The incidence of PE + NPD (0.37%) was lower than the incidence of PE-only (1.04%), representing around a third of the total yearly incidence of PE. Incident PE + NPD was, in comparison with PE-only, differentially characterised by poor functioning, environmental risks, PRS-Sz, positive family history, prescription of antipsychotic medication and (mental) health service use. The risk in 'clinical high risk' states is mediated not by attenuated psychosis per se but specifically the combination of attenuated psychosis and NPD. CHR-P/APS research should be reconceptualised from a focus on attenuated psychotic symptoms with exclusion of non-psychotic DSM-disorders, as the 'pure' representation of a supposedly homotypic psychosis risk state, towards a focus on poor-outcome NPDs, characterised by a degree of psychosis admixture, on the pathway to psychotic disorder outcomes.

Association of preceding psychosis risk states and non-psychotic mental disorders with incidence of clinical psychosis in the general population: a prospective study in the NEMESIS-2 cohort.

The validity and clinical utility of the concept of "clinical high risk" (CHR) for psychosis have so far been investigated only in risk-enriched samples in clinical settings. In this population-based prospective study, we aimed - for the first time - to assess the incidence rate of clinical psychosis and es-timate the population attributable fraction (PAF) of that incidence for preceding psychosis risk states and DSM-IV diagnoses of non-psychotic mental disorders (mood disorders, anxiety disorders, alcohol use disorders, and drug use disorders). All analyses were adjusted for age, gender and education. The incidence rate of clinical psychosis was 63.0 per 100,000 person-years. The mutually-adjusted Cox proportional hazards model indicated that preceding diagnoses of mood disorders (hazard ratio, HR=10.67, 95% CI: 3.12-36.49), psychosis high-risk state (HR=7.86, 95% CI: 2.76-22.42) and drug use disorders (HR=5.33, 95% CI: 1.61-17.64) were associated with an increased risk for clinical psychosis incidence. Of the clinical psychosis incidence in the population, 85.5% (95% CI: 64.6-94.1) was attributable to prior psychopathology, with mood disorders (PAF=66.2, 95% CI: 33.4-82.9), psychosis high-risk state (PAF=36.9, 95% CI: 11.3-55.1), and drug use disorders (PAF=18.7, 95% CI: -0.9 to 34.6) as the most important factors. Although the psychosis high-risk state displayed a high relative risk for clinical psychosis outcome even after adjusting for other psychopathology, the PAF was comparatively low, given the low prevalence of psychosis high-risk states in the population. These findings provide empirical evidence for the "prevention paradox" of targeted CHR early intervention. A comprehensive prevention strategy with a focus on broader psychopathology may be more effective than the current psychosis-focused approach for achieving population-based improvements in prevention of psychotic disorders.

Altered Trisynaptic Hippocampal Network Regions in Psychosis Risk States: An Integrated Hippocampal Shape and Subregion Study Using Ultra-High Field MRI Data

Hippocampal abnormalities are widely reported in schizophrenia and in psychosis-risk states. Given the complexity of hippocampal structure/function, we conducted a highly refined in vivo examination targeting regions involved in the trisynaptic circuit (dentate gyrus, CA1 and CA3) along with hippocampal shape using a high-field MRI (7T) among familial high-risk (n=15; age=30.53±4.13 years) and control (n=33; age=28.85±4.27 years) subjects.

The DSM-5 proposal for attenuated psychosis syndrome: a history.

This article narrates a consensus history of the proposal to include diagnostic criteria for a psychosis risk syndrome in the DSM-5, in part, to document what happened, but also to potentially help focus future efforts at clinically useful early detection. The purpose of diagnosing a risk state would be to slow and ideally prevent the development of the full disorder. Concerns about diagnosing a psychosis risk state included a high false positive rate, potentially harmful use of anti-psychotic medication with people who would not transition to psychosis, and stigmatization. Others argued that educating professionals about what 'risk' entails could reduce inappropriate treatments. During the revision, the proposal shifted from diagnosing risk to emphasizing current clinical need associated with attenuated psychotic symptoms. Within the community of researchers who studied psychosis risk, people disagreed about whether risk and/or attenuated symptoms should be an official DSM-5 diagnosis. Once it became clear that the DSM-5 field trials did not include enough cases to establish the reliability of the proposed criteria, everyone agreed that the criteria should be put in a section on conditions for further study rather the main section of the DSM-5. We close with recommendations about some practical benchmarks that should be met for including criteria for early detection in the classification system.

Worldwide implementation of clinical services for the prevention of psychosis: The IEPA early intervention in mental health survey.

Clinical research into the Clinical High Risk state for Psychosis (CHR-P) has allowed primary indicated prevention in psychiatry to improve outcomes of psychotic disorders. The strategic component of this approach is the implementation of clinical services to detect and take care of CHR-P individuals, which are recommended by several guidelines. The actual level of implementation of CHR-P services worldwide is not completely clear. To assess the global geographical distribution, core characteristics relating to the level of implementation of CHR-P services; to overview of the main barriers that limit their implementation at scale. CHR-P services worldwide were invited to complete an online survey. The survey addressed the geographical distribution, general implementation characteristics and implementation barriers. The survey was completed by 47 CHR-P services offering care to 22 248 CHR-P individuals: Western Europe (51.1%), North America (17.0%), East Asia (17.0%), Australia (6.4%), South America (6.4%) and Africa (2.1%). Their implementation characteristics included heterogeneous clinical settings, assessment instruments and length of care offered. Most CHR-P patients were recruited through mental or physical health services. Preventive interventions included clinical monitoring and crisis management (80.1%), supportive therapy (70.2%) or structured psychotherapy (61.7%), in combination with pharmacological treatment (in 74.5%). Core implementation barriers were staffing and financial constraints, and the recruitment of CHR-P individuals. The dynamic map of CHR-P services has been implemented on the IEPA website: https://iepa.org.au/list-a-service/. Worldwide primary indicated prevention of psychosis in CHR-P individuals is possible, but the implementation of CHR-P services is heterogeneous and constrained by pragmatic challenges.

Predictors of remission from the ultra-high risk state for psychosis.

A significant proportion of individuals at Ultra-High Risk (UHR) for psychosis do not transition to manifest psychosis. Many non-transitioning UHR individuals do, however, display poor long-term outcomes such as persistence of attenuated psychotic symptoms. Evidence is scarce on which variables may predict a better clinical and functional prognosis such as remission from the UHR state. A total of 146 UHR individuals were enrolled in a randomized clinical trial (RCT), with this being analyses secondary to the RCT. Participants were assessed on multiple domains of symptoms, functioning, neuro- and social cognition. Regression analyses elucidated on the predictive power of these measures to remission from the UHR status (ie, not meeting UHR criteria) at 12-month follow-up. Of the 91 UHR individuals attending 12-month follow-up, 33 (36%) exhibited remission from the UHR state. Regression analyses revealed baseline functioning to be a significant predictor of risk remission, and this was maintained when controlling for the effect of antipsychotic medication, gender and estimated IQ. The individuals with remission from the UHR state showed lower attenuated psychotic- and depressive symptoms along with better functioning at 12-month follow-up. Our findings indicate functioning to be a contributor to the symptomatic recovery of UHR individuals, but a large amount of the variance on risk remission is, however, explained by other factors. Additionally, our findings suggest that UHR individuals with better functioning at ascertainment may present with a better clinical and functional prognosis, which may inform on the need for monitoring and intervention in this subgroup.

Improving the Detection of Individuals at Clinical Risk for Psychosis in the Community, Primary and Secondary Care: An Integrated Evidence-Based Approach.

Background: The first rate-limiting step for improving outcomes of psychosis through preventive interventions in people at clinical high risk for psychosis (CHR-P) is the ability to accurately detect individuals who are at risk for the development of this disorder. Currently, this detection power is sub-optimal. Methods: This is a conceptual and nonsystematic review of the literature, focusing on the work conducted by leading research teams in the field. The results will be structured in the following sections: understanding the CHR-P assessment, validity of the CHR-P as a universal risk state for psychosis, and improving the detection of at-risk individuals in secondary mental health care, in primary care, and in the community. Results: CHR-P instruments can provide adequate prognostic accuracy for the prediction of psychosis provided that they are employed in samples who have undergone risk enrichment during recruitment. This substantially limits their detection power in real-world settings. Furthermore, there is initial evidence that not all cases of psychosis onset are preceded by a CHR-P stage. A transdiagnostic individualized risk calculator could be used to automatically screen secondary mental health care medical notes to detect those at risk of psychosis and refer them to standard CHR-P assessment. Similar risk estimation tools for use in primary care are under development and promise to boost the detection of patients at risk in this setting. To improve the detection of young people who may be at risk of psychosis in the community, it is necessary to adopt digital and/or sequential screening approaches. These solutions are based on recent scientific evidence and have potential for implementation internationally. Conclusions: The best strategy to improve the detection of patients at risk for psychosis is to implement a clinical research program that integrates different but complementary detection approaches across community, primary, and secondary care. These solutions are based on recent scientific advancements in the development of risk estimation tools and e-health approaches and have the potential to be applied across different clinical settings.

Assessing Developmental Environmental Risk Factor Exposure in Clinical High Risk for Psychosis Individuals: Preliminary Results Using the Individual and Structural Exposure to Stress in Psychosis-Risk States Scale.

Introduction: Exposure to cumulative environmental risk factors across development has been linked to a host of adverse health/functional outcomes. This perspective incorporating information regarding exposure at differing developmental periods is lacking in research surrounding individuals at Clinical High Risk (CHR) for developing a psychotic disorder. Methods: CHR individuals (n = 35) and healthy volunteers (n = 28) completed structured clinical interviews as well as our group’s newly developed Individual and Structural Exposure to Stress in Psychosis-risk-states (ISESP) interview. Lifetime cumulative scores were calculated, and severity of stress was reported for multiple developmental periods/ages. Group differences were tested, and associations with current symptom domains were examined. Results: Significant group differences were not observed for lifetime cumulative events, though CHR trended toward endorsing more events and greater stress severity. For stress severity across development, there were trending group differences for the 11–13 age range, and significant group differences for the 14–18 age range; notably, comparisons for earlier time points did not approach statistical significance. Associations between negative symptoms and cumulative severity of exposure were observed. Discussion: Results suggest exploring exposure to cumulative environmental risk factors/stressors and stress severity across developmental periods is generally informative and possibly specifically so for predictive models and diathesis-stress psychosis risk conceptualizations.

Cognition, psychosis risk and metabolic measures in two adolescent birth cohorts.

Psychoses, especially schizophrenia, are often preceded by cognitive deficits and psychosis risk states. Altered metabolic profiles have been found in schizophrenia. However, the associations between metabolic profiles and poorer cognitive performance and psychosis risk in the population remain to be determined. Detailed molecular profiles were measured for up to 8976 individuals from two general population-based prospective birth cohorts: the Northern Finland Birth Cohort 1986 (NFBC 1986) and the Avon Longitudinal Study of Parents and Children (ALSPAC). A high-throughput nuclear magnetic resonance spectroscopy platform was used to quantify 70 metabolic measures at age 15-16 years in the NFBC 1986 and at ages 15 and 17 years in ALSPAC. Psychosis risk was assessed using the PROD-screen questionnaire at age 15-16 years in the NFBC 1986 or the psychotic-like symptoms assessment at age 17 years in ALSPAC. Cognitive measures included academic performance at age 16 years in both cohorts and general intelligence and executive function in ALSPAC. Logistic regression measured cross-sectional and longitudinal associations between metabolic measures and psychosis risk and cognitive performance, controlling for important covariates. Seven metabolic measures, primarily fatty acid (FA) measures, showed cross-sectional associations with general cognitive performance, four across both cohorts (low density lipoprotein diameter, monounsaturated FA ratio, omega-3 ratio and docosahexaenoic acid ratio), even after controlling for important mental and physical health covariates. Psychosis risk showed minimal metabolic associations. FA ratios may be important in marking risk for cognitive deficits in adolescence. Further research is needed to clarify whether these biomarkers could be causal and thereby possible targets for intervention.

The Italian Version of the Brief 21-Item Prodromal Questionnaire: Field Test, Psychometric Properties and Age-Sensitive Cut-Offs

Background: The Brief, 21-item version of the Prodromal Questionnaire (PQ-B) is a promising screener for psychosis-risk states that could be implemented in routine clinical practice. In this study, we assessed psychometric properties of the Italian version of the PQ-B (iPQ-B) in a sample of 243 help-seekers, aged 13–35 years. Sampling and Methods: After completing the iPQ-B, participants were assessed with the Comprehensive Assessment of At-Risk Mental States (CAARMS). Diagnostic accuracy (sensitivity, specificity, positive and negative predictive values [PPV and NPV], positive and negative likelihood ratios) and concurrent validity between PQ-B and CAARMS were determined using Cronbach’s alpha and Cohen’s kappa. We also tested the validity of the adopted PQ-B cut-offs through Receiver Operating Characteristic (ROC) curves plotted against CAARMS diagnoses and the predictive validity of the iPQ-B at 1-year follow-up. Results: The iPQ-B showed high internal consistency (Cronbach’s alpha = 0.868), acceptable diagnostic accuracy and concurrent validity (70% sensitivity, 67% specificity, 81% PPV, Cohen’s kappa = 0.335). ROC analyses pointed to threshold of ≥20 on the PQ-B total distress score as best cut-off. After 12 months of follow-up, 11% of participants who scored ≥4 on the PQ-B distressing item total score and did not meet CAARMS psychosis criteria at baseline, developed a psychotic disorder. Interestingly, age had significant negative correlations with iPQ-B scores and adolescents (aged < 18 years) showed higher iPQ-B scores than young adults. Conclusions: Overall, the psychometric properties of the iPQ-B were satisfactory. As iPQ-B scores appeared inversely associated to age, age-tailored cut-off scores are recommended for screening purposes in child-adolescent cohorts.