Intervention in Individuals at Ultra-High Risk for Psychosis: A Review and Future Directions

Centre for Youth Mental Health, Orygen Youth Health Research Centre, University of Melbourne, Victoria, Australia.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 07/2009; 70(9):1206-12. DOI: 10.4088/JCP.08r04472
Source: PubMed


Over the last 15 years, a focus on early intervention in psychotic disorders has emerged. Initially, the early psychosis movement focused on timely recognition and phase-specific treatment of first-episode psychosis. However, early psychosis researchers suspected that pushing the point of intervention even further back to the prodromal phase of psychotic disorders may result in even better outcomes. This article reviews intervention research in the ultra-high-risk phase of psychotic disorders.
A literature search of intervention trials with ultra-high-risk cohorts published after 1980 was conducted on PubMed with the search terms prodrome and intervention.
All published intervention trials with ultra-high-risk cohorts.
The first generation of intervention trials indicated that both pharmacologic and psychological intervention strategies may be of value in terms of symptom reduction and delay or prevention of onset of threshold psychotic disorder.
Further controlled intervention trials with larger sample sizes are required in order to confirm and extend these findings. We argue that the clinical staging model provides a framework for the rationale and design of such studies, with simpler, safer, and more benign interventions being better candidates for first-line treatment, while more complex and potentially harmful treatments should be reserved for those cases in which response has failed to occur. Recent evidence indicates that neuroprotective agents, such as essential fatty acids, may be a suitable form of intervention for the ultra-high-risk phase of psychotic disorders, with a positive risk-benefit balance. Ethical aspects have become more salient given the recently observed declining transition rate in ultra-high-risk samples. We outline the key questions for the next generation of ultra-high-risk intervention trials.

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    • "likelihood of psychosis prevention) as well as costs (direct medical costs, side-effects, etc.) (Essock et al., 2002; McNeil and Kaij, 1979). Applications of the present work might include treatment monitoring, integration with other evaluations , and programs of stepwise application of treatments, all in the context of prudent counseling (McGorry et al., 2009). "
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    ABSTRACT: Background: Improving predictive accuracy is of paramount importance for early detection and prevention of psychosis. We sought a symptom severity classifier that would improve psychosis risk prediction. Methods: Subjects were from two cohorts of the North American Prodrome Longitudinal Study. All subjects met Criteria of Psychosis-Risk States. In Cohort-1 (n=296) we developed a classifier that included those items of the Scale of Psychosis-Risk Symptoms that best distinguished subjects who converted to psychosis from nonconverters, with performance initially validated by randomization tests in Cohort-1. Cohort-2 (n=592) served as an independent test set. Results: We derived 2-Item and 4-Item subscales. Both included unusual thought content and suspiciousness; the latter added reduced ideational richness and difficulties with focus/concentration. The Concordance Index (C-Index), a measure of discrimination, was similar for each subscale across cohorts (4-Item subscale Cohort-2: 0.71, 95% CI=[0.64, 0.77], Cohort-1: 0.74, 95% CI=[0.69, 0.80]; 2-Item subscale Cohort-2: 0.68, 95% CI=[0.3, 0.76], Cohort-1: 0.72, 95% CI=[0.66-0.79]). The 4-Item performed better than the 2-Item subscale in 742/1000 random selections of 80% subsets of Cohort-2 subjects (p-value=1.3E-55). Subscale calibration between cohorts was proportional (higher scores/lower survival), but absolute conversion risk predicted from Cohort-1 was higher than that observed in Cohort-2, reflecting the cohorts' differences in 2-year conversion rates (Cohort-2: 0.16, 95% CI=[0.13, 0.19]; Cohort-1: 0.30, 95% CI=[0.24, 0.36]). Conclusion: Severity of unusual thought content, suspiciousness, reduced ideational richness, and difficulty with focus/concentration informed psychosis risk prediction. Scales based on these symptoms may have utility in research and, assuming further validation, eventual clinical applications.
    Schizophrenia Research 10/2015; DOI:10.1016/j.schres.2015.09.008 · 3.92 Impact Factor
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    • "Pioneering work on the trajectory of BP has identified early-risk syndromes that precede the official onset (Akiskal et al., 1985; Duffy et al., 2014; Mesman et al., 2013) and are proposed to represent early stages in the development of BP (Duffy et al., 2014). Identifying the early stages of BP is important for prevention and early intervention strategies, which have been shown to be successful in early psychosis and can avert or delay the transition from clinically ultra-high-risk conditions to a full psychotic disorder (McGorry et al., 2009). The early symptoms (and syndromes) that precede full-blown BP are usually non-specific during childhood (e.g., anxiety, sleep disturbance, and attention deficit hyperactivity disorder (ADHD) symptoms/signs) and then manifest as adjustment disorder during early adolescence and later as subthreshold depression and/or hypomania that falls short of the official criteria (Akiskal et al., 1985; Correll et al., 2014; Duffy et al., 2014; Egeland et al., 2000; Mesman et al., 2013). "
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    ABSTRACT: Background: Validating the high-risk (HR) and ultra-high-risk (UHR) stages of bipolar disorder (BP) may help enable early intervention strategies. Methods: We followed up with 44 offspring of parents with BP, subdividing into the HR and UHR categories. The offspring were aged 8-28 years and were free of any current DSM-IV diagnoses. Our multilevel, integrative approach encompassed gray matter (GM) volumes, brain network connectivity, neuropsychological performance, and clinical outcomes. Findings: Compared with the healthy controls (HCs) (n = 33), the HR offspring (n = 26) showed GM volume reductions in the right orbitofrontal cortex. Compared with the HR offspring, the UHR offspring (n = 18) exhibited increased GM volumes in four regions. Both the HR and UHR offspring displayed abnormalities in the inferior occipital cortex regarding the measures of degree and centrality, reflecting the connections and roles of the region, respectively. In the UHR versus the HR offspring, the UHR offspring exhibited upwards-shifted small world topologies that reflect high clustering and efficiency in the brain networks. Compared with the HCs, the UHR offspring had significantly lower assortativity, which was suggestive of vulnerability. Finally, processing speed, visual-spatial, and general function were impaired in the UHR offspring but not in the HR offspring. Interpretation: The abnormalities observed in the HR offspring appear to be inherited, whereas those associated with the UHR offspring represent stage-specific changes predisposing them to developing the disorder.
    10/2015; 2(8):917-26. DOI:10.1016/j.ebiom.2015.06.027
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    • "Focus on the early detection and intervention in psychosis has spread all over the world in the past 20 years (McGorry, 1993; McGlashan, 1996; Birchwood et al., 1998; Cocchi et al., 2008; McGorry et al., 2009; De Koning et al., 2009). Emphasis on this model has renewed interest in the assessment of vulnerability traits for psychosis in both the schizophrenia and the bipolar disorder spectra (Stefanis et al., 2004; Kwapil et al., 2008; Barrantes-Vidal et al., 2009; 2010; Kwapil et al., 2011; Walsh et al., 2012; Fonseca- Pedrero et al., 2012). "
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    ABSTRACT: Sparse evidence of a co-aggregation of the risk of schizophrenia and bipolar disorder provides support for a shared but nonspecific genetic etiology of bipolar disorder and schizophrenia. Temperaments are conceptualized as trait sub-syndromic conditions of major pathologies. This study set out to test the hypothesis of a continuum between schizotypy and affective temperaments versus the alternative hypothesis of their independence based on a cross-sectional, survey design involving 649 (males: 47%) college students. The short 39-item TEMPS-A and the SPQ were used as measures of the affective temperaments and of schizotypy, respectively. Confirmatory factor analyses were applied to a unidimensional model, to a standard correlate traits model, to second-order representations of a common latent structure, and to a bifactor model. Confirmatory bifactor modeling provided evidence against a complete independence of the dimensions subsumed by the affective and the schizotypal traits. The best solution distinguished between two sub-domains grouping positive symptoms and negative symptoms as measured by the SPQ subscales, and a sub-domain related to the affective temperaments as measured by the TEMPS-A. Limitations due to the use of subscales from two different tools should be taken into account.
    Psychiatry Research 11/2014; 225(1-2). DOI:10.1016/j.psychres.2014.10.027 · 2.47 Impact Factor
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