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BACKGROUND: Disruptions of axonal connectivity are thought to be a core pathophysiological feature of psychotic illness, but whether they are present early in the illness, prior to antipsychotic exposure, and whether they can predict clinical outcome remains unknown. METHODS: We acquired diffusion-weighted MRI to map structural connectivity between each pair of 319 parcellated brain regions in 61 antipsychotic-naive individuals with First Episode Psychosis (FEP; 15-25 years, 46% female) and a demographically matched sample of 27 control participants, along with clinical follow-up data in patients three months and 12 months after the scan. We used connectome-wide analyses to map disruptions of inter-regional pairwise connectivity and connectome-based predictive modelling to predict longitudinal change in symptoms and functioning. RESULTS: Individuals with FEP showed disrupted connectivity in a brain-wide network linking all brain regions when compared with controls (pFWE=.03). Baseline structural connectivity significantly predicted change in functioning over 12 months (r=.44;pFWE=.041), such that lower connectivity within fronto-striato-thalamic systems predicted worse functional outcomes. CONCLUSIONS: Brain-wide reductions of structural connectivity exist during the early stages of psychotic illness and cannot be attributed to antipsychotic medication. Moreover, baseline measures of structural connectivity can predict change in patient functional outcomes up to one year after engagement with treatment services.
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BACKGROUND AND HYPOTHESIS: Cognition has been associated with socio-occupational functioning in individuals at Clinical High Risk for Psychosis (CHR-P). The present study hypothesized that clustering CHR-P participants based on cognitive data could reveal clinically meaningful subtypes. STUDY DESIGN: A cohort of 291 CHR-P subjects was recruited through the multicentre EU-GEI high-risk study. We explored whether an underlying cluster structure was present in the cognition data. Clustering of cognition data was performed using k-means clustering and density-based spatial clustering of applications with noise. Cognitive subtypes were validated by comparing differences in functioning, psychosis symptoms, transition outcome, and grey matter volume between clusters. Network analysis was used to further examine relationships between cognition scores and clinical symptoms. STUDY RESULTS: No underlying cluster structure was found in the cognitive data. K-means clustering produced "spared" and "impaired" cognition clusters similar to those reported in previous studies. However, these clusters were not associated with differences in functioning, symptomatology, outcome, or grey matter volume. Network analysis identified cognition and symptoms/functioning measures that formed separate subnetworks of associations. CONCLUSIONS: Stratifying patients according to cognitive performance has the potential to inform clinical care. However, we did not find evidence of cognitive clusters in this CHR-P sample. We suggest that care needs to be taken in inferring the existence of distinct cognitive subtypes from unsupervised learning studies. Future research in CHR-P samples could explore the existence of cognitive subtypes across a wider range of cognitive domains.
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Aims: To map studies assessing both clinical high risk for psychosis (CHR-P) and borderline personality disorder (BPD) in clinical samples, focusing on clinical/research/preventive paradigms and proposing informed research recommendations. Methods: We conducted a PRISMA-ScR/JBI-compliant scoping review (protocol: https://osf.io/8mz7a) of primary research studies (cross-sectional/longitudinal designs) using valid measures/criteria to assess CHR-P and BPD (threshold/subthreshold) in clinical samples, reporting on CHR-P/psychotic symptoms and personality disorder(s) in the title/abstract/keywords, identified in Web of Science/PubMed/(EBSCO)PsycINFO until 23/08/2023. Results: 33 studies were included and categorized into four themes reflecting their respective clinical/research/preventive paradigm: (i) BPD as a comorbidity in CHR-P youth (k = 20), emphasizing early detection and intervention in psychosis; (ii) attenuated psychosis syndrome (APS) as a comorbidity among BPD inpatients (k = 2), with a focus on hospitalized adolescents/young adults admitted for non-psychotic mental disorders; (iii) mixed samples (k = 7), including descriptions of early intervention services and referral pathways; (iv) transdiagnostic approaches (k = 4) highlighting "clinical high at risk mental state" (CHARMS) criteria to identify a pluripotent risk state for severe mental disorders. Conclusion: The scoping review reveals diverse approaches to clinical care for CHR-P and BPD, with no unified treatment strategies. Recommendations for future research should focus on: (i) exploring referral pathways across early intervention clinics to promote timely intervention; (ii) enhancing early detection strategies in innovative settings such as emergency departments; (iii) improving mental health literacy to facilitate help-seeking behaviors; (iv) analysing comorbid disorders as complex systems to better understand and target early psychopathology; (v) investigating prospective risk for BPD; (vi) developing transdiagnostic interventions; (vii) engaging youth with lived experience of comorbidity to gain insight on their subjective experience; (viii) understanding caregiver burden to craft family-focused interventions; (ix) expanding research in underrepresented regions such as Africa and Asia, and; (x) evaluating the cost-effectiveness of early interventions to determine scalability across different countries. Systematic Review Registration: https://osf.io/8mz7a.
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Decreased white matter (WM) integrity and disturbance in fatty acid composition have been reported in individuals at ultra-high risk of psychosis (UHR). The current study is the first to investigate both WM integrity and erythrocyte membrane polyunsaturated fatty acid (PUFA) levels as potential risk biomarkers for persistent UHR status, and global functioning in UHR individuals. Forty UHR individuals were analysed at baseline for erythrocyte membrane PUFA concentrates. Tract-based spatial statistics (TBSS) was used to analyse fractional anisotropy (FA) and diffusivity measures. Measures of global functioning and psychiatric symptoms were evaluated at baseline and at 12-months. Fatty acids and WM indices did not predict functional outcomes at baseline or 12-months. Significant differences were found in FA between UHR remitters and non-remitters (individuals who no longer met UHR criteria versus those who continued to meet criteria at 12-months). Docosahexaenoic acid (DHA) was found to be a significant predictor of UHR status at 12-months, as was the interaction between the sum of Ï-3 and whole brain FA, and the interaction between the right anterior limb of the internal capsule and the sum of Ï-3. The results confirm that certain fatty acids have a unique relationship with WM integrity in UHR individuals.
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Membrana Eritrocítica , Vaina de Mielina , Trastornos Psicóticos , Humanos , Trastornos Psicóticos/metabolismo , Trastornos Psicóticos/diagnóstico por imagen , Trastornos Psicóticos/patología , Masculino , Femenino , Membrana Eritrocítica/metabolismo , Adulto Joven , Adolescente , Vaina de Mielina/metabolismo , Vaina de Mielina/patología , Anisotropía , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Sustancia Blanca/metabolismo , Ácidos Grasos/metabolismo , Adulto , Imagen de Difusión Tensora , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/patología , Ácidos Docosahexaenoicos/metabolismo , Escalas de Valoración Psiquiátrica , Ácidos Grasos Insaturados/metabolismoRESUMEN
Globally, 75% of depressive, bipolar, and psychotic disorders emerge by age 25 years. However, these disorders are often preceded by non-specific symptoms or attenuated clinical syndromes. Difficulties in determining optimal treatment interventions for these emerging mental disorders, and uncertainties about accounting for co-occurring psychopathology and illness trajectories, have led many youth mental health services to adopt transdiagnostic clinical staging frameworks. In this Health Policy paper, an international working group highlights ongoing challenges in applying transdiagnostic staging frameworks in clinical research and practice, and proposes refinements to the transdiagnostic model to enhance its reliability, consistent recording, and clinical utility. We introduce the concept of within-stage heterogeneity and describe the advantages of defining stage in terms of clinical psychopathology and stage modifiers. Using examples from medicine, we discuss the utility of categorising stage modifiers into factors associated with progression (ie, potential predictors of stage transition) and extension (ie, factors associated with the current presentation that add complexity to treatment selection). Lastly, we suggest how it is possible to revise the currently used transdiagnostic staging approach to incorporate these key concepts, and how the revised framework could be applied in clinical and research practice.
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Trastornos Mentales , Humanos , Adolescente , Trastornos Mentales/terapia , Trastornos Mentales/diagnóstico , Reproducibilidad de los Resultados , Adulto Joven , Servicios de Salud Mental/normas , Salud Mental , Progresión de la Enfermedad , AdultoRESUMEN
Importance: Psychiatric disorders may come and go with symptoms changing over a lifetime. This suggests the need for a paradigm shift in diagnosis and treatment. Here we present a fresh look inspired by dynamical systems theory. This theory is used widely to explain tipping points, cycles, and chaos in complex systems ranging from the climate to ecosystems. Observations: In the dynamical systems view, we propose the healthy state has a basin of attraction representing its resilience, while disorders are alternative attractors in which the system can become trapped. Rather than an immutable trait, resilience in this approach is a dynamical property. Recent work has demonstrated the universality of generic dynamical indicators of resilience that are now employed globally to monitor the risks of collapse of complex systems, such as tropical rainforests and tipping elements of the climate system. Other dynamical systems tools are used in ecology and climate science to infer causality from time series. Moreover, experiences in ecological restoration confirm the theoretical prediction that under some conditions, short interventions may invoke long-term success when they flip the system into an alternative basin of attraction. All this implies practical applications for psychiatry, as are discussed in part 2 of this article. Conclusions and Relevance: Work in the field of dynamical systems points to novel ways of inferring causality and quantifying resilience from time series. Those approaches have now been tried and tested in a range of complex systems. The same tools may help monitoring and managing resilience of the healthy state as well as psychiatric disorders.
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Trastornos Mentales , Humanos , Trastornos Mentales/psicología , Resiliencia Psicológica , Teoría de SistemasRESUMEN
Importance: Dynamical systems theory is widely used to explain tipping points, cycles, and chaos in complex systems ranging from the climate to ecosystems. It has been suggested that the same theory may be used to explain the nature and dynamics of psychiatric disorders, which may come and go with symptoms changing over a lifetime. Here we review evidence for the practical applicability of this theory and its quantitative tools in psychiatry. Observations: Emerging results suggest that time series of mood and behavior may be used to monitor the resilience of patients using the same generic dynamical indicators that are now employed globally to monitor the risks of collapse of complex systems, such as tropical rainforest and tipping elements of the climate system. Other dynamical systems tools used in ecology and climate science open ways to infer personalized webs of causality for patients that may be used to identify targets for intervention. Meanwhile, experiences in ecological restoration help make sense of the occasional long-term success of short interventions. Conclusions and Relevance: Those observations, while promising, evoke follow-up questions on how best to collect dynamic data, infer informative timescales, construct mechanistic models, and measure the effect of interventions on resilience. Done well, monitoring resilience to inform well-timed interventions may be integrated into approaches that give patients an active role in the lifelong challenge of managing their resilience and knowing when to seek professional help.
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Trastornos Mentales , Humanos , Trastornos Mentales/psicología , Trastornos Mentales/terapia , Resiliencia Psicológica , Teoría de SistemasRESUMEN
BACKGROUND: Labeling terms for high-risk state for psychosis, such as 'ultra-high risk' (UHR), 'attenuated psychosis syndrome' (APS), and 'at-risk mental state' (ARMS), have been criticized for their potential to lead to stigma. Hence, mental health service users in Melbourne recently proposed new terms illustrating the at-risk concept ['pre-diagnosis stage' (PDS), 'potential of developing a mental illness' (PDMI), and 'disposition for developing a mental illness' (DDMI)]. We aimed at testing the suitability of these existing and new terms in the clinical settings of early psychiatric intervention in Japan. METHODS: At two centers of early intervention (Toyama and Tokyo), a questionnaire on the understanding and opinion of high-risk terminology was administered to 62 high-risk patients, 44 caregivers, and 64 clinicians. The questionnaire contained the existing and new terms, where the term ARMS was translated into two different Japanese terms ARMS-psychosis and ARMS-kokoro. Participants' opinion on the disclosure of high-risk status was also obtained. RESULTS: ARMS-kokoro was most preferred, least stigmatizing, and best explaining the patients' difficulties for all groups, while UHR and other terms including the Japanese word 'psychosis' (i.e., APS and ARMS-psychosis) were not preferred. New labeling terms were generally not well received. All groups preferred full disclosure of high-risk terms by the psychiatrist with or without the presence of family members. CONCLUSION: The term ARMS-kokoro was commonly accepted as a favorable labeling term for the high-risk state for psychosis in Japan. However, another translation ARMS-psychosis was considered stigmatizing, demonstrating the importance of appropriate translation of high-risk terminology into local languages.
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Cuidadores , Trastornos Psicóticos , Terminología como Asunto , Humanos , Trastornos Psicóticos/epidemiología , Japón , Cuidadores/psicología , Masculino , Femenino , Adulto , Adulto Joven , Encuestas y Cuestionarios , Personal de Salud/estadística & datos numéricos , Riesgo , Estigma Social , Adolescente , Persona de Mediana EdadRESUMEN
AIM: Lithium, even at low doses, appears to offer neuroprotection against a wide variety of insults. In this controlled pilot, we examined the safety (i.e., side-effect profile) of lithium in a sample of young people identified at ultra-high risk (UHR) for psychosis. The secondary aim was to explore whether lithium provided a signal of clinical efficacy in reducing transition to psychosis compared with treatment as usual (TAU). METHODS: Young people attending the PACE clinic at Orygen, Melbourne, were prescribed a fixed dose (450 mg) of lithium (n = 25) or received TAU (n = 78). The primary outcome examined side-effects, with transition to psychosis, functioning and measures of psychopathology assessed as secondary outcomes. RESULTS: Participants in both groups were functionally compromised (lithium group GAF = 56.6; monitoring group GAF = 56.9). Side-effect assessment indicated that lithium was well-tolerated. 64% (n = 16) of participants in the lithium group were lithium-adherent to week 12. Few cases transitioned to psychosis across the study period; lithium group 4% (n = 1); monitoring group 7.7% (n = 6). There was no difference in time to transition to psychosis between the groups. No group differences were observed in other functioning and symptom domains, although all outcomes improved over time. CONCLUSIONS: With a side-effect profile either comparable to, or better than UHR antipsychotic trials, lithium might be explored for further research with UHR young people. A definitive larger trial is needed to determine the efficacy of lithium in this cohort.
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Despite the functional impact of cognitive deficit in people with psychosis, objective cognitive assessment is not typically part of routine clinical care. This is partly due to the length of traditional assessments and the need for a highly trained administrator. Brief, automated computerised assessments could help to address this issue. We present data from an evaluation of PsyCog, a computerised, non-verbal, mini battery of cognitive tests. Healthy Control (HC) (N = 135), Clinical High Risk (CHR) (N = 233), and First Episode Psychosis (FEP) (N = 301) participants from a multi-centre prospective study were assessed at baseline, 6 months, and 12 months. PsyCog was used to assess cognitive performance at baseline and at up to two follow-up timepoints. Mean total testing time was 35.95 min (SD = 2.87). Relative to HCs, effect sizes of performance impairments were medium to large in FEP patients (composite score G = 1.21, subtest range = 0.52-0.88) and small to medium in CHR patients (composite score G = 0.59, subtest range = 0.18-0.49). Site effects were minimal, and test-retest reliability of the PsyCog composite was good (ICC = 0.82-0.89), though some practice effects and differences in data completion between groups were found. The present implementation of PsyCog shows it to be a useful tool for assessing cognitive function in people with psychosis. Computerised cognitive assessments have the potential to facilitate the evaluation of cognition in psychosis in both research and in clinical care, though caution should still be taken in terms of implementation and study design.
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This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.
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Trastornos Psicóticos , Esquizofrenia , Humanos , Estudios Prospectivos , Adulto , Síntomas Prodrómicos , Adulto Joven , Cooperación Internacional , Adolescente , Proyectos de Investigación/normas , Masculino , FemeninoRESUMEN
BACKGROUND: We examined the course of illness over a 12-month period in a large, international multi-center cohort of people with a first-episode schizophrenia spectrum disorder (FES) in a naturalistic, prospective study (PSYSCAN). METHOD: Patients with a first episode of schizophrenia, schizoaffective disorder (depressive type) or schizophreniform disorder were recruited at 16 institutions in Europe, Israel and Australia. Participants (N = 304) received clinical treatment as usual throughout the study. RESULTS: The mean age of the cohort was 24.3 years (SD = 5.6), and 67 % were male. At baseline, participants presented with a range of intensities of psychotic symptoms, 80 % were taking antipsychotic medication, 68 % were receiving psychological treatment, with 46.5 % in symptomatic remission. The mean duration of untreated psychosis was 6.2 months (SD = 17.0). After one year, 67 % were in symptomatic remission and 61 % were in functional remission, but 31 % had been readmitted to hospital at some time after baseline. In the cohort as a whole, depressive symptoms remained stable over the follow-up period. In patients with a current depressive episode at baseline, depressive symptoms slightly improved. Alcohol, tobacco and cannabis were the most commonly used substances, with daily users of cannabis ranging between 9 and 11 % throughout the follow-up period. CONCLUSIONS: This study provides valuable insight into the early course of a broad range of clinical and functional aspects of illness in FES patients in routine clinical practice.
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Antipsicóticos , Trastornos Psicóticos , Esquizofrenia , Humanos , Masculino , Adulto Joven , Adulto , Femenino , Esquizofrenia/epidemiología , Esquizofrenia/terapia , Esquizofrenia/diagnóstico , Estudios de Cohortes , Estudios Prospectivos , Resultado del Tratamiento , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/terapia , Trastornos Psicóticos/diagnóstico , Antipsicóticos/uso terapéutico , Estudios de SeguimientoRESUMEN
BACKGROUND: The majority of individuals at ultra-high risk (UHR) for psychosis do not transition to a full threshold psychotic disorder. It is therefore important to understand their longer-term clinical and functional outcomes, particularly given the high prevalence of comorbid mental disorders in this population at baseline. AIMS: This study investigated the prevalence of non-psychotic disorders in the UHR population at entry and long-term follow-up and their association with functional outcomes. Persistence of UHR status was also investigated. STUDY DESIGN: The sample comprised 102 UHR young people from the Personal Assessment and Crisis Evaluation (PACE) Clinic who had not transitioned to psychosis by long-term follow-up (meanâ =â 8.8 years, rangeâ =â 6.8-12.1 years since baseline). RESULTS: Eighty-eight percent of participants at baseline were diagnosed with at least one mental disorder, the majority of which were mood disorders (78%), anxiety disorders (35%), and substance use disorders (SUDs) (18%). This pattern of disorder prevalence continued at follow-up, though prevalence was reduced, with 52% not meeting criteria for current non-psychotic mental disorder. However, 35% of participants developed a new non-psychotic mental disorder by follow-up. Presence of a continuous non-psychotic mental disorder was associated with poorer functional outcomes at follow-up. 28% of participants still met UHR criteria at follow-up. CONCLUSIONS: The study adds to the evidence base that a substantial proportion of UHR individuals who do not transition to psychosis experience persistent attenuated psychotic symptoms and persistent and incident non-psychotic disorders over the long term. Long-term treatment and re-entry into services is indicated.
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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.
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Trastornos Psicóticos , Humanos , Trastornos Psicóticos/genética , Psicopatología/métodos , Longevidad/genéticaRESUMEN
A set of clinical criteria, the Clinical High At-Risk Mental State (CHARMS) criteria, have been developed to identify symptomatic young people who are at-risk of disorder progression. The current study aimed to validate the CHARMS criteria by testing whether they prospectively identify individuals at-risk of progressing from attenuated symptomatology to a first episode of serious mental disorder, namely first episode psychosis, first episode mania, severe major depression, and borderline personality disorder. 121 young people completed clinical evaluations at baseline, 6- and 12-month follow-up. The Kaplan-Meier method was used to assess transition rates. Cox regression and LASSO were used to examine baseline clinical predictors of transition. Linear mixed effects modelling was used to examine symptom severity. 28 % of CHARMS+ individuals transitioned to a Stage 2 disorder by 12-month follow-up. The CHARMS+ group had more severe symptoms at follow-up than the CHARMS- group. 96 % of Stage 2 transitions were initially to severe depression. Meeting criteria for multiple CHARMS subgroups was associated with higher transition risk: meeting one at-risk group = 24 %; meeting two at-risk groups = 17 %, meeting three at-risk groups = 55 %, meeting four at-risk groups = 50 %. The strongest baseline predictor of transition was severity of depressive symptoms. The CHARMS criteria identified a group of individuals at-risk of imminent onset of severe mental disorder, particularly severe depression. Larger scale studies and longer follow-up periods are required to validate and extend these findings.
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Trastorno de Personalidad Limítrofe , Trastorno Depresivo Mayor , Trastornos Psicóticos , Humanos , Adolescente , Trastornos Psicóticos/diagnóstico , Trastorno Depresivo Mayor/diagnóstico , Trastorno de Personalidad Limítrofe/diagnóstico , ManíaRESUMEN
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.
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Trastornos Psicóticos , Aislamiento Social , Humanos , Trastornos Psicóticos/psicología , Aislamiento Social/psicología , Masculino , Femenino , Adulto Joven , Adolescente , Adulto , Evaluación Ecológica Momentánea , Distrés Psicológico , Estrés Psicológico/psicología , Factores de RiesgoRESUMEN
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 nâ =â 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% (nâ =â 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.
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Biomarcadores , Síntomas Prodrómicos , Proteómica , Trastornos Psicóticos , Humanos , Trastornos Psicóticos/sangre , Femenino , Masculino , Biomarcadores/sangre , Adulto Joven , Adolescente , Adulto , Progresión de la Enfermedad , Estudios Longitudinales , RiesgoRESUMEN
AIM: Basic self disturbance is a putative core vulnerability marker of schizophrenia spectrum disorders. The primary aims of the Self, Neuroscience and Psychosis (SNAP) study are to: (1) empirically test a previously described neurophenomenological self-disturbance model of psychosis by examining the relationship between specific clinical, neurocognitive, and neurophysiological variables in UHR patients, and (2) develop a prediction model using these neurophenomenological disturbances for persistence or deterioration of UHR symptoms at 12-month follow-up. METHODS: SNAP is a longitudinal observational study. Participants include 400 UHR individuals, 100 clinical controls with no attenuated psychotic symptoms, and 50 healthy controls. All participants complete baseline clinical and neurocognitive assessments and electroencephalography. The UHR sample are followed up for a total of 24 months, with clinical assessment completed every 6 months. RESULTS: This paper presents the protocol of the SNAP study, including background rationale, aims and hypotheses, design, and assessment procedures. CONCLUSIONS: The SNAP study will test whether neurophenomenological disturbances associated with basic self-disturbance predict persistence or intensification of UHR symptomatology over a 2-year follow up period, and how specific these disturbances are to a clinical population with attenuated psychotic symptoms. This may ultimately inform clinical care and pathoaetiological models of psychosis.
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Trastornos Psicóticos , Esquizofrenia , Humanos , Factores de Riesgo , Trastornos Psicóticos/psicología , Esquizofrenia/diagnóstico , Estudios Longitudinales , Atención , Escalas de Valoración PsiquiátricaRESUMEN
Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Design, Setting, and Participants: This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. Main Outcomes and Measures: For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores. Results: Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD) age was 22.32 (4.95) years. Individuals with CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z scores, and all ADS values. For any given region, the proportion of individuals with CHR-P who had infranormal or supranormal values was low (up to 153 individuals [<11.42%]) and similar to that of healthy individuals (<115 individuals [<9.30%]). Individuals with CHR-P who converted to a psychotic disorder had a higher percentage of infranormal values in temporal regions compared with those who did not convert (7.01% vs 1.38%) and healthy individuals (5.10% vs 0.89%). In the CHR-P group, only the ADS SA was associated with positive symptoms (ß = -0.08; 95% CI, -0.13 to -0.02; P = .02 for false discovery rate) and IQ (ß = 0.09; 95% CI, 0.02-0.15; P = .02 for false discovery rate). Conclusions and Relevance: In this case-control study, findings suggest that macroscale neuromorphometric measures may not provide an adequate explanation of psychosis risk.
Asunto(s)
Trastornos Psicóticos , Humanos , Masculino , Adulto Joven , Adulto , Femenino , Estudios de Casos y Controles , Trastornos Psicóticos/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Neuroimagen , Cognición , Síntomas ProdrómicosRESUMEN
BACKGROUND: Multimodal modeling that combines biological and clinical data shows promise in predicting transition to psychosis in individuals who are at ultra-high risk. Individuals who transition to psychosis are known to have deficits at baseline in cognitive function and reductions in gray matter volume in multiple brain regions identified by magnetic resonance imaging. METHODS: In this study, we used Cox proportional hazards regression models to assess the additive predictive value of each modality-cognition, cortical structure information, and the neuroanatomical measure of brain age gap-to a previously developed clinical model using functioning and duration of symptoms prior to service entry as predictors in the Personal Assessment and Crisis Evaluation (PACE) 400 cohort. The PACE 400 study is a well-characterized cohort of Australian youths who were identified as ultra-high risk of transitioning to psychosis using the Comprehensive Assessment of At Risk Mental States (CAARMS) and followed for up to 18 years; it contains clinical data (from N = 416 participants), cognitive data (n = 213), and magnetic resonance imaging cortical parameters extracted using FreeSurfer (n = 231). RESULTS: The results showed that neuroimaging, brain age gap, and cognition added marginal predictive information to the previously developed clinical model (fraction of new information: neuroimaging 0%-12%, brain age gap 7%, cognition 0%-16%). CONCLUSIONS: In summary, adding a second modality to a clinical risk model predicting the onset of a psychotic disorder in the PACE 400 cohort showed little improvement in the fit of the model for long-term prediction of transition to psychosis.