Twelve-month psychosis-predictive value of the ultra-high risk criteria in children and adolescents
Introduction
Psychoses are one of the most severe disorders in children and adolescents (CAD) (Gore et al., 2011). Their poor outcome generally correlates positively with the durations of untreated psychosis (DUP) and illness (DUI) (Marshall et al., 2005). Outcome is even worse in early-onset psychosis (EOP), with the first episode starting before the age of 18 years (Rabinowitz et al., 2006).
Compared with adult-onset psychosis (AOP), the poorer outcome of EOP might not be intrinsic, but due to a significantly longer DUP (Schimmelmann et al., 2007, Schimmelmann et al., 2008). Furthermore, clinically, EOP often presents slightly differently compared with AOP (Gochman et al., 2011, Tiffin and Welsh, 2013). Thus, the challenges of early detection and treatment of first signs of the emerging disorder may be different in EOP and also in AOP with an illness onset in childhood and early adolescence compared with AOP that has an onset in late adolescence and adulthood (Schimmelmann and Schultze-Lutter, 2012, Schimmelmann et al., 2013a, Schimmelmann et al., 2013b).
Two approaches for an early detection of psychoses currently prevail: the “ultra-high risk” (UHR) (Yung et al., 1998), mainly relying on attenuated psychotic symptoms (APS) and the “basic symptoms” (Schultze-Lutter et al., 2012). The alternative UHR criteria, which comprise the attenuated psychotic symptom (APS) criterion, the brief intermittent psychotic symptom (BIPS) criterion, and the genetic risk and functional decline (GRFD) criterion, were originally developed with the explicit aim of detecting an imminent risk for psychoses, i.e., persons at risk for developing a first-episode within the next 12 months (Schultze-Lutter et al., 2015). In contrast to the UHR criteria, the criteria based on basic symptoms, i.e., the cognitive-perceptive basic symptoms, (COPER) criterion and the cognitive disturbances (COGDIS) criterion (Schultze-Lutter et al., 2012), were developed to detect the risk for psychosis as early as possible in the development of the illness, ideally before functional impairments have appeared (Schultze-Lutter et al., 2015).
A recent meta-analysis showed pooled conversion rates in UHR samples that increased from 9.6% at 6 months to 37.0% at > 4-year follow-up, with significantly lower conversion rates in 12- to 18-year-olds (Schultze-Lutter et al., 2015). Lower conversion rates in CAD might not be surprising as current risk criteria were developed and validated in predominately adult samples (age ≥ 16 years; Schultze-Lutter et al., 2015, Yung et al., 1998).
CAD studies reporting high prevalence of (attenuated) psychotic symptoms (hallucinations) in the general population further indicated age-related peculiarities of UHR symptoms (Schimmelmann et al., 2013a, Schimmelmann et al., 2013b). These seem to decrease throughout adolescence (Kelleher et al., 2012b, Brandizzi et al., 2014, Schimmelmann et al., 2015) and remit spontaneously in about three quarters of CAD (Bartels-Velthuis et al., 2011).
Thus, it was recently argued that the validity of current risk criteria needs to be examined in and possibly adapted to CAD populations (National Institute for Health and Clinical Excellence NICE, 2013, Schimmelmann and Schultze-Lutter, 2012, Schimmelmann et al., 2013a, Schultze-Lutter et al., 2012, Schultze-Lutter et al., 2015).
To address this need, we investigated predictors of 1-year outcome in CAD at increased risk of psychosis in terms of both predictors of conversion to psychosis and of outcome of non-converters (remission and persistence of UHR criteria versus conversion).
Section snippets
Participants
The sample consisted of 35 patients (aged 9–17-years, n = 7 (20%) each age 9–11 and 16–17) with suspected EOP at the Child and Adolescent Neuropsychiatry Unit of the Children Hospital Bambino Gesù in Rome from 2012 to 2013 (Table 1). Inclusion criterion was the presence of any UHR criterion (Yung et al., 1998): APS, brief intermittent psychotic symptoms (BIPS) and/or genetic risk plus functional deterioration (GRFD). Exclusion criteria were: past or present psychosis, traumatic brain injury or
One-year outcome
Within 1 year, 7 (20.0%) patients developed an EOP (schizophrenia), while 9 (25.7%) remitted from UHR status, which persisted in 19 (54.3%) patients. No significant differences across age groups revealed (AG1: χ2(4) = 1.38, p = 0.848; AG2: χ2(2) = 1.06, p = 0.588), indicating a small age effect on outcome (AG1: V = 0.140; AG2: V = 0.174). Furthermore, neither in general nor on item-level did BIPS or APS reveal any significant age group difference at baseline, and a moderate effect only revealed for APS in
Discussion
Addressing the need to examine the validity of UHR criteria in and possibly adapt them to CAD (National Institute for Health and Clinical Excellence NICE, 2013, Schimmelmann et al., 2013a, Schimmelmann et al., 2013b, Schimmelmann et al., 2015, Schultze-Lutter et al., 2015), we examined the 1-year outcome in 35 CAD meeting UHR criteria, thereby including children below the age of 12 for the first time. We found a fifth of patients developing psychosis; schizophrenia in all cases. UHR status
Strengths and limitations
Our sample differs from other adolescent UHR samples in several aspects: (1) Being recruited at a hospital that is an Italian point of reference for the assessment and treatment of psychosis in CAD participants had been referred rather on the suspicion of a first episode of EOP than on that of a still developing psychosis as is usual when referring to an early detection service. Thus, similar to early UHR samples, our sample likely represents a more severe spectrum of the UHR state with high
Conclusions
Our findings provide first evidence for the predictive utility of UHR criteria in CAD in terms of BIPS when accompanied by signs of cognitive impairment, i.e., disorganized communication. Yet, as APS related to both thought content and perception were rather indicative of non-conversion at 1-year follow-up, their use in early detection of psychosis in CAD needs further study. Overall, the need for more in-depth studies into developmental peculiarities in the early detection and treatment of
Conflicts of interest
The authors have no conflict of interest to declare related to the content of this study.
Role of funding source
None.
Contributors
Dr. Armando designed this large First Episode Outcome Study. Dr. Pontillo, Dr. Decrescenzo, Dr. Mazzone, Dr. Monducci, Dr. Lo Cascio, Dr. Santonastaso and Dr. Pucciarini collected the data. Dr. Armando and Dr. Schultze-Lutter analyzed and interpreted the data. Dr. Armando, Dr. Schultze-Lutter, Dr. Vicari and Dr. Schimmelmann wrote the first draft of the manuscript. All contributed to and have approved the final manuscript.
Acknowledgments
Marco Armando was supported by the Brain and Behavior Research Foundation (21278) (formerly NARSAD).
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