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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. [ABSTRACT FROM AUTHOR]

• Docosahexaenoic acid plays an important role in ultra-high risk of psychosis status. • Fractional anisotropy significantly differed in ultra-high risk of psychosis remitters versus non-remitters. • Specific fatty acids showed a unique link to white matter integrity in ultra-high-risk individuals. 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 ώ-3 and whole brain FA, and the interaction between the right anterior limb of the internal capsule and the sum of ώ-3. The results confirm that certain fatty acids have a unique relationship with WM integrity in UHR individuals. [ABSTRACT FROM AUTHOR]

Intervention at the earliest illness stage, in ultra or clinical high-risk individuals, or indicated prevention, currently represents the most promising strategy to ameliorate, delay or prevent psychosis. We review the current state of evidence and conduct a broad-spectrum meta-analysis of various outcomes: transition to psychosis, attenuated positive and negative psychotic symptoms, mania, depression, anxiety, general psychopathology, symptom-related distress, functioning, quality of life, and treatment acceptability. 26 randomized controlled trials were included. Meta-analytically pooled interventions reduced transition rate (risk ratio [RR] = 0.57, 95%CI 0.41–0.81) and attenuated positive psychotic symptoms at 12-months (standardized mean difference = −0.15, 95%CI = -0.28–-0.01). When stratified by intervention type (pharmacological, psychological), only the pooled effect of psychological interventions on transition rate was significant. Cognitive behavioral therapy (CBT) was associated with a reduction in incidence at 12-months (RR = 0.52, 95%CI = 0.33–0.82) and 18–48-months (RR = 0.60, 95%CI = 0.42–0.84), but not 6-months. Findings at 12-months and 18–48-months were robust in sensitivity and subgroup analyses. All other outcomes were non-significant. To date, effects of trialed treatments are specific to transition and, a lesser extent, attenuated positive symptoms, highlighting the future need to target other symptom domains and functional outcomes. Sound evidence supports CBT in reducing transition and the value of intervening at this illness stage. Research Registry ID: reviewregistry907. • This meta-analysis of 26 randomized controlled trials (N = 2351) examined the efficacy of interventions for ultra-high risk for psychosis. • Psychological interventions pooled, and cognitive behavioral, reduced transition to psychosis at 12-months and up to 4 years follow-up. • Treatments also had a small effect on attenuated positive psychotic symptoms at 12-months. • It is feasible to prevent or delay the onset of psychotic disorders through preventive interventions that are safe and effective. • A broad range of head-to-head treatment studies that target the full spectrum of clinical and functional outcomes is needed. [ABSTRACT FROM AUTHOR]