The Ultra-High-Risk for psychosis groups: Evidence to maintain the status quo
Introduction
It has been two decades since Yung and colleagues (Yung and McGorry, 1996a) introduced a set of standardised criteria to identify individuals at Ultra-High-Risk (UHR) of developing a psychotic disorder (also known as the At Risk Mental State or ‘prodromal’ phase of psychosis). Since this time, the UHR paradigm has provided a window into risk factors and aetiological mechanisms involved in psychosis onset and an opportunity to trial preventive interventions (van der Gaag et al., 2013). To be considered UHR, help-seeking individuals must be in the age range of highest risk for psychosis (late adolescence, early adulthood) and meet one or more of the following 3 criteria: 1) Attenuated Psychotic Symptoms (APS): sub-threshold positive psychotic symptoms during the past 12 months; 2) Brief Limited Intermittent Psychotic Symptoms (BLIPS): frank psychotic symptoms for less than one week which resolve spontaneously; 3) Genetic vulnerability (Trait) – meet criteria for Schizotypal Personality Disorder or have a first-degree relative with a psychotic disorder. Each risk criteria must also be associated with a deterioration in functioning or chronic low functioning.2
Over the years, evidence has pointed to variability between groups defined by these UHR criteria in relation to risk of transitioning to a psychotic disorder (Fusar-Poli et al., 2015, Nelson et al., 2011, Nelson et al., 2013). A history of BLIPS (regardless of APS or Trait risk) has consistently been linked to the highest risk of transitioning to a psychotic disorder (Fusar-Poli et al., 2015, Nelson et al., 2011, Nelson et al., 2013). Presumed genetic vulnerability (Trait) with no history of APS or BLIPS (Trait-only) confers the lowest transition risk (Fusar-Poli et al., 2015, Nelson et al., 2011). An early study found that the combination of genetic vulnerability and APS (Trait + APS) was strongly predictive of transition to psychosis by twelve months (Yung et al., 2004). However, more recent evidence suggests similar risk trajectories for Trait + APS individuals and individuals who meet APS criteria alone (APS-only) (Fusar-Poli et al., 2015, Nelson et al., 2011).
Evidence of variability in transition risk has prompted some researchers to challenge the current composition of the UHR criteria. In a guidance paper for the European Psychiatric Association, Schultz-Lutter and colleagues recommended that having a first-degree relative with a psychotic illness should not be considered a clinical marker of risk for psychosis even in the presence of functional decline (Schultze-Lutter et al., 2015). Others have proposed that BLIPS should be treated as a separate clinical entity based on both higher transition risk and diagnostic overlap with DSM/ICD brief psychotic disorders (Fusar-Poli et al., 2015).
Concurrently, it has become increasingly evident that clinical implications of UHR status extend beyond risk of transition to psychosis. Most individuals who meet UHR criteria will not develop a psychotic disorder (Nelson et al., 2013, Simon et al., 2011) but will experience persistent Attenuated Psychotic Symptoms (de Wit et al., 2014, Simon et al., 2011), poor psychosocial functioning (Rutigliano et al., 2016a) and high rates of non-psychotic disorders (de Wit et al., 2014, Lin et al., 2015, Rutigliano et al., 2016b). Such findings have driven a reframing of UHR as a clinical state signifying pluripotent, transdiagnostic risk and the need for clinical care, rather than simply a marker of psychosis risk (McGorry et al., 2006, McGorry and Nelson, 2016, Yung et al., 2012).
In the current study we investigated possible differences between the UHR groups in clinical risk other than transition to psychosis. Specifically, we examined baseline clinical characteristics known to contribute to poor outcomes in UHR populations, including symptom severity (Fusar-Poli et al., 2013, Nelson et al., 2013, Seidman et al., 2010), psychosocial functioning (Nelson et al., 2013, Seidman et al., 2010), duration of symptoms prior to first contact with clinical services (Nelson et al., 2013) and the year that individuals entered clinical services (Nelson et al., 2013, Simon et al., 2014, Yung et al., 2007). We also examined long-term non-transition outcomes including symptom severity, psychosocial functioning and the prevalence of non-psychotic disorders. A large cohort (N = 702) of UHR individuals were recruited at entry to treatment early psychosis clinical service and re-assessed up to thirteen years later. For consistency with previous studies (Fusar-Poli et al., 2015, Nelson et al., 2011), we defined four combinations of UHR risk group: Trait-only, APS-only, Trait + APS, and any BLIPS (regardless of Trait or APS criteria). If the UHR groups defined here engender truly distinct psychopathological risk profiles, we would expect group differences to emerge in baseline characteristics and long-term non-transition outcomes.
Section snippets
Participants and setting
The present sample (N = 702) were recruited between 1995 and 2013, across 10 research sites in Australia (Melbourne, Sydney), the Netherlands (Amsterdam), Germany (Jena), Switzerland (Basel, Zurich), Austria (Vienna), Denmark (Copenhagen), Singapore, and Hong Kong (Pok Fu Lam). Each site has an established early psychosis clinical service that conducts research with UHR clients. From 1995 to 2006 participants were recruited for UHR research studies at the Melbourne site only (N = 398). These
Sample characteristics
Table 2 presents baseline demographic and clinical characteristics for each of the four risk groups. As illustrated, the APS-only group were, on average, younger at baseline than Trait-only (p < 0.001) and Trait + APS (p = 0.018) and any BLIPS (p = 0.026) individuals. Groups also differed in terms of year recruited into the study (baseline year: 1995–1999, 2000–2006, 2010–2013) largely driven by a decline in any BLIPS and an increase in APS-only in later years (see Fig. 1 and Table 2). Consequently,
Discussion
In recent years the criteria that define UHR groups have been called into question due to differences observed between these groups in transition risk (Fusar-Poli et al., 2015, Schultze-Lutter et al., 2015). At the same time, it has become evident that as a clinical entity UHR status reflects more than simply a marker of psychosis risk, and may be more aptly considered a transdiagnostic risk state signifying the need for clinical care (van Os and Guloksuz, 2017). The present study thus aimed to
Funding
This work was funded by the Colonial Foundation Philanthropic Trust; Stanley Medical Research Institute (#07TGF-1102 f), and National Health and Medical Research Council Program Grant (#566529 and #350241). The Authors have declared that there are no conflicts of interest in relation to the subject of this study.
Conflict of interest
The Authors have declared that there are no conflicts of interest in relation to the subject of this study.
Acknowledgments
The authors would especially like to thank the participants of all the studies and the researchers involved in the original research studies.
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