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Psychotic symptoms are typically measured using clinical ratings, but more objective and sensitive metrics are needed. Hence, we will assess thought disorder using the Research Domain Criteria (RDoC) heuristic for language production, and its recommended paradigm of "linguistic corpus-based analyses of language output". Positive thought disorder (e.g., tangentiality and derailment) can be assessed using word-embedding approaches that assess semantic coherence, whereas negative thought disorder (e.g., concreteness, poverty of speech) can be assessed using part-of-speech (POS) tagging to assess syntactic complexity. We aim to establish convergent validity of automated linguistic metrics with clinical ratings, assess normative demographic variance, determine cognitive and functional correlates, and replicate their predictive power for psychosis transition among at-risk youths. This study will assess language production in 450 English-speaking individuals in Australia and Canada, who have recent onset psychosis, are at clinical high risk (CHR) for psychosis, or who are healthy volunteers, all well-characterized for cognition, function and symptoms. Speech will be elicited using open-ended interviews. Audio files will be transcribed and preprocessed for automated natural language processing (NLP) analyses of coherence and complexity. Data analyses include canonical correlation, multivariate linear regression with regularization, and machine-learning classification of group status and psychosis outcome. This prospective study aims to characterize language disturbance across stages of psychosis using computational approaches, including psychometric properties, normative variance and clinical correlates, important for biomarker development. SPEAK will create a large archive of language data available to other investigators, a rich resource for the field. [ABSTRACT FROM AUTHOR]

Background: People with schizophrenia have high rates of substance use which contributes to co-morbidity and premature mortality. Some evidence suggests people at-risk for psychosis have high rates of substance use. We aimed to assess substance use in a help-seeking cohort, comparing those at-risk and not at-risk for psychosis, and to establish any relationship with clinical symptoms.Method: Participants were help-seeking youth presenting to mental health services in Sydney and Melbourne. 279 (34.8%) were at-risk for psychosis, and 452 (56.4%) did not meet criteria for a psychotic disorder or risk for psychosis. The excluded individuals were made up of 59 (7.4%) young people who met criteria for a psychotic disorder and 11 (1.4%) who were unable to be evaluated. We assessed the association of substance use involvement with risk status and clinical symptoms using multivariate regression.Results: Individuals at-risk for psychosis had significantly higher tobacco, alcohol and cannabis use than those not at-risk. Multivariate analysis revealed at-risk status was significantly associated with higher alcohol involvement scores when adjusting for age and gender, but no association was found for cannabis or tobacco. At-risk status was no longer associated with alcohol involvement when cannabis or tobacco use was added into the analysis.Conclusion: Tobacco smoking, alcohol consumption and cannabis use are common in help-seeking youth, particularly those at-risk for psychosis. It is important to consider co-occurring use of different substances in adolescents. Early substance misuse in this phase of illness could be targeted to improve physical and mental health in young people. [ABSTRACT FROM AUTHOR]

Abstract: There is now strong evidence of progressive neuropathological processes in bipolar disorder (BD). On this basis, the current understanding of the neurobiology of BD has shifted from an initial focus on monoamines, subsequently including evidence of changes in intracellular second messenger systems and more recently to, incorporating changes in inflammatory cytokines, corticosteroids, neurotrophins, mitochondrial energy generation, oxidative stress and neurogenesis into a more comprehensive model capable of explaining some of the clinical features of BD. These features include progressive shortening of the inter-episode interval with each recurrence, occurring in consort with reduced probability of treatment response as the illness progresses. To this end, emerging data shows that these biomarkers may differ between early and late stages of BD in parallel with stage-related structural and neurocognitive alterations. This understanding facilitates identification of rational therapeutic targets, and the development of novel treatment classes. Additionally, these pathways provide a cogent explanation for the efficacy of seemingly diverse therapies used in BD, that appear to share common effects on oxidative, inflammatory and neurotrophic pathways. [ABSTRACT FROM AUTHOR]

Background: Individuals with first-episode psychosis demonstrate high rates of suicide attempt (SA).Aims: 1) To examine the prevalence of, and risk factors for, SA in a first-episode psychosis (FEP) cohort over a 7.4 year follow-up period. 2) To investigate differences between single versus multiple suicide attempters.Methods: This study reports baseline and follow-up data from a naturalistic, prospective follow-up of 413 FEP patients treated at a specialist early psychosis centre. Assessments were conducted at treatment entry, initial symptom remission or stabilization, and long term follow-up. Binary logistic regression models were used to assess unadjusted and adjusted associations between early illness and sociodemographic characteristics and two outcome measures: any SA during follow-up; and multiple SAs.Results: Follow-up data were available for 282 participants. Sixty-one (21.6%) made a suicide attempt over the follow-up period, including 12 successful suicides. The following baseline risk factors increased the risk of any SA: history of self-harm (OR=4.27; p<0.001), suicidal tendencies (OR=2.30; p=0.022), being depressed for >50% of the initial psychotic episode (OR=2.49; p=0.045), and hopelessness (OR=2.03; p=0.030). History of problem alcohol use increased the risk of multiple SAs (OR=4.43; 95% CI (1.05-18.7); p=0.043).Discussion: The prevalence of suicide attempt in this study exceeds reports from short-term FEP studies but is comparable to longer term follow-up studies, indicating that risk remains elevated for at least 7 years following commencement of treatment. The key predictor of future suicide attempt was previous self-harm, indicating that interventions for self-harm are required. [ABSTRACT FROM AUTHOR]