Development and temporal validation of a clinical prediction model of transition to psychosis in individuals at ultra-high risk in the UHR 1000+ cohort.

The concept of ultra-high risk for psychosis (UHR) has been at the forefront of psychiatric research for several decades, with the ultimate goal of preventing the onset of psychotic disorder in high-risk individuals. Orygen (Melbourne, Australia) has led a range of observational and intervention studies in this clinical population. These datasets have now been integrated into the UHR 1000+ cohort, consisting of a sample of 1,245 UHR individuals with a follow-up period ranging from 1 to 16.

Psychosis Risk: Time to Look Empirically at a First-step Economical-pragmatic Way to Examine Anomalous Self-experience. Exploring the SQuEASE-11.

Background: Since the late 1990s, there has been a worldwide surge of scientific interest in the pre-psychotic phase, resulting in the introduction of several clinical tools for early detection. The predictive accuracy of these tools has been limited, motivating the need for methodological and perspectival improvements. The EASE manual supports systematic assessment of anomalous self-experience, and proposes an overall model of understanding how most psychotic experiences may be initially generated on the basis of a unifying, fundamental, pre-reflective distortion of subjectivity.

Brainwide Anatomical Connectivity and Prediction of Longitudinal Outcomes in Antipsychotic-Naïve First-Episode Psychosis.

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 remain unknown.

Methods: We acquired diffusion-weighted magnetic resonance images to map structural connectivity between each pair of 319 parcellated brain regions in 61 antipsychotic-naïve individuals with first-episode psychosis (15-25 years, 46% female) and a demographically matched sample of 27 control participants. Clinical follow-up data were also acquired in patients 3 and 12 months after the scan.

An open label pilot trial of low-dose lithium for young people at ultra-high risk for psychosis.

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.

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis.

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.

Psychopathology and psychosocial functioning among young people with first-episode psychosis and/or first-presentation borderline personality disorder.

Background: One in five young people with first-episode psychosis (FEP) also presents with borderline personality disorder (BPD) features. Among people diagnosed with BPD, auditory verbal hallucinations occur in 29-50 % and delusions in 10-100 %. Co-occurrence of psychotic symptoms and BPD is associated with greater clinical severity and greater difficulty accessing evidence based FEP care.

Transdiagnostic risk identification: A validation study of the Clinical High At Risk Mental State (CHARMS) criteria.

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.

Combining Clinical With Cognitive or Magnetic Resonance Imaging Data for Predicting Transition to Psychosis in Ultra High-Risk Patients: Data From the PACE 400 Cohort.

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 self, neuroscience and psychosis study: Testing a neurophenomenological model of the onset of psychosis.

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.

A Sequential Adaptive Intervention Strategy Targeting Remission and Functional Recovery in Young People at Ultrahigh Risk of Psychosis: The Staged Treatment in Early Psychosis (STEP) Sequential Multiple Assignment Randomized Trial.

Importance: Clinical trials have not established the optimal type, sequence, and duration of interventions for people at ultrahigh risk of psychosis.

Objective: To determine the effectiveness of a sequential and adaptive intervention strategy for individuals at ultrahigh risk of psychosis.

Design, Setting, And Participants: The Staged Treatment in Early Psychosis (STEP) sequential multiple assignment randomized trial took place within the clinical program at Orygen, Melbourne, Australia.

The Addition of Fish Oil to Cognitive Behavioral Case Management for Youth Depression: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial.

Background: Clinical trials suggest that long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) (fish oil) may reduce depressive symptoms in adults with major depressive disorder. Therefore, n-3 PUFAs may be a potential treatment for depression in youth.

Methods: Participants were 15- to-25 year-old individuals with major depressive disorder who sought care in one of three government-funded mental health services for young people in metropolitan Melbourne, Perth, or Sydney, Australia.

Effects of risperidone/paliperidone versus placebo on cognitive functioning over the first 6 months of treatment for psychotic disorder: secondary analysis of a triple-blind randomised clinical trial.

The drivers of cognitive change following first-episode psychosis remain poorly understood. Evidence regarding the role of antipsychotic medication is primarily based on naturalistic studies or clinical trials without a placebo arm, making it difficult to disentangle illness from medication effects. A secondary analysis of a randomised, triple-blind, placebo-controlled trial, where antipsychotic-naive patients with first-episode psychotic disorder were allocated to receive risperidone/paliperidone or matched placebo plus intensive psychosocial therapy for 6 months was conducted.

Gradients of striatal function in antipsychotic-free first-episode psychosis and schizotypy.

Both psychotic illness and subclinical psychosis-like experiences (PLEs) have been associated with cortico-striatal dysfunction. This work has largely relied on a discrete parcellation of the striatum into distinct functional areas, but recent evidence suggests that the striatum comprises multiple overlapping and smoothly varying gradients (i.e.

The association between stressful experiences and OCD symptoms in young adults at transdiagnostic risk.

Background: It is unclear whether there is a specific association between stressful experiences and obsessive-compulsive symptoms or whether this relationship is due to stressful experiences increasing risk for psychopathology generally.

Aims: The current study examined the association between stressful experiences and obsessive-compulsive symptom dimensions, while adjusting for coexisting psychiatric symptoms and psychological distress in a young adult transdiagnostic at-risk sample.

Methods: Forty-three participants completed self-report measures assessing obsessive-compulsive symptoms, stressful experiences, and a range of other psychiatric symptoms.

Isolating the impact of antipsychotic medication on metabolic health: Secondary analysis of a randomized controlled trial of antipsychotic medication versus placebo in antipsychotic medication naïve first-episode psychosis (the STAGES study).

Background: Cardiovascular and metabolic diseases are the leading contributors to the early mortality associated with psychotic disorders. To date, it has not been possible to disentangle the effect of medication and non-medication factors on the physical health of people with a first episode of psychosis (FEP). This study aimed to isolate the effects of antipsychotic medication on anthropometric measurements, fasting glucose and lipids.

Effects of omega-3 polyunsaturated fatty acid supplementation on cognitive functioning in youth at ultra-high risk for psychosis: secondary analysis of the NEURAPRO randomised controlled trial.

Background: Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population.

Aims: To investigate whether omega-3 polyunsaturated fatty acid (-3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis.

Intelligence trajectories in individuals at ultra-high risk for psychosis: An 8-year longitudinal analysis.

Cognitive impairment is a well-documented predictor of transition to a full-threshold psychotic disorder amongst individuals at ultra-high risk (UHR) for psychosis. However, less is known about whether change in cognitive functioning differs between those who do and do not transition. Studies to date have not examined trajectories in intelligence constructs (e.

Pineal morphology of the clinical high-risk state for psychosis and different psychotic disorders.

Background: Pineal volume reductions have been reported in schizophrenia and clinical high-risk states for the development of psychosis, supporting the role of melatonin dysregulation in the pathophysiology of psychosis. However, it remains unclear whether pineal volume is associated with the later onset of psychosis in individuals at clinical high-risk (CHR) of psychosis or if pineal atrophy is specific to schizophrenia among different psychotic disorders.

Methods: This magnetic resonance imaging study examined the volume of and cyst prevalence in the pineal gland in 135 individuals at CHR of psychosis [52 (38.

Baseline data of a sequential multiple assignment randomized trial (STEP study).

Aim: Research has shown that preventative intervention in individuals at ultra-high risk of psychosis (UHR) improves symptomatic and functional outcomes. The staged treatment in early psychosis (STEP) trial aims to determine the most effective type, timing and sequence of interventions in the UHR population by sequentially studying the effectiveness of (1) support and problem solving, (2) cognitive-behavioural case management and (3) antidepressant medication with an embedded fast-fail option of (4) omega-3 fatty acids or low-dose antipsychotic medication. This paper presents the recruitment flow and baseline clinical characteristics of the sample.

Twelve-Month Cognitive Trajectories in Individuals at Ultra-High Risk for Psychosis: A Latent Class Analysis.

Understanding longitudinal cognitive performance in individuals at ultra-high risk for psychosis (UHR) is important for informing theoretical models and treatment. A vital step in this endeavor is to determine whether there are UHR subgroups that have similar patterns of cognitive change over time. The aims were to: i) identify latent class trajectories of cognitive performance over 12-months in UHR individuals, ii) identify baseline demographic and clinical predictors of the resulting classes, and iii) determine whether trajectory classes were associated with transition to psychosis or functional outcomes.

Characterization and prediction of clinical pathways of vulnerability to psychosis through graph signal processing.

Causal interactions between specific psychiatric symptoms could contribute to the heterogenous clinical trajectories observed in early psychopathology. Current diagnostic approaches merge clinical manifestations that co-occur across subjects and could significantly hinder our understanding of clinical pathways connecting individual symptoms. Network analysis techniques have emerged as alternative approaches that could help shed light on the complex dynamics of early psychopathology.

Cannabidiol for at risk for psychosis youth: A randomized controlled trial.

Background: No biological treatment has been firmly established for the at-risk stage of psychotic disorder. In this study we aim to test if subthreshold psychotic symptoms can be effectively treated with cannabidiol (CBD), a non-psychoactive compound of the plant Cannabis sativa. The question has taken on increased importance in the wake of evidence questioning both the need and efficacy of specific pharmacological interventions in the ultra-high risk (UHR) for psychosis group.