Improving the clinical prediction of psychosis by combining ultra-high risk criteria and cognitive basic symptoms Frauke Schultze-Lutter a, ⁎, Joachim Klosterkötter b , Stephan Ruhrmann b a University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bolligenstr. 111, 3000 Bern 60, Switzerland b University of Cologne, Department of Psychiatry and Psychotherapy, Kerpener Str. 62, 50937 Cologne, Germany abstract article info Article history: Received 1 September 2013 Received in revised form 30 January 2014 Accepted 14 February 2014 Available online 7 March 2014 Keywords: Ultra-high risk Attenuated psychotic symptom Basic symptom Cognitive disturbances Prediction Cognition Objective: Cognitive impairments are regarded as a core component of schizophrenia. However, the cognitive dimension of psychosis is hardly considered by ultra-high risk (UHR) criteria. Therefore, we studied whether the combination of symptomatic UHR criteria and the basic symptom criterion “cognitive disturbances” (COGDIS) is superior in predicting first-episode psychosis. Method: In a naturalistic 48-month follow-up study, the conversion rate to first-episode psychosis was studied in 246 outpatients of an early detection of psychosis service (FETZ); thereby, the association between conversion, and the combined and singular use of UHR criteria and COGDIS was compared. Results: Patients that met UHR criteria and COGDIS (n = 127) at baseline had a significantly higher risk of conversion (hr = 0.66 at month 48) and a shorter time to conversion than patients that met only UHR criteria (n = 37; hr = 0.28) or only COGDIS (n = 30; hr = 0.23). Furthermore, the risk of conversion was higher for the combined criteria than for UHR criteria (n = 164; hr = 0.56 at month 48) and COGDIS (n = 158; hr = 0.56 at month 48) when considered irrespective of each other. Conclusions: Our findings support the merits of considering both COGDIS and UHR criteria in the early detection of per- sons who are at high risk of developing a first psychotic episode within 48 months. Applying both sets of criteria im- proves sensitivity and individual risk estimation, and may thereby support the development of stage-targeted interventions. Moreover, since the combined approach enables the identi fication of considerably more homogeneous at-risk samples, it should support both preventive and basic research. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Current models of psychoses assume a stepwise process in the formation of positive symptoms: neurobiological changes result in im- paired information processing and, consequently, in aberrant experiences (Garety et al., 2001; Kapur, 2003). Thus, cognitive impairment as defined by deficient neurocognitive test performance is integral to the develop- ment of psychosis, and “impaired cognition” is one of the eight “dimen- sions of psychotic symptom severity” proposed in DSM-5 (APA, 2013, p. 743f). Yet, the cognitive dimension is not considered in the ultra-high risk (UHR) criteria of psychosis (Yung et al., 1998; Miller et al., 1999). 1.1. Cognitive impairments in early at-risk stages Small-to-medium impairments in the neurocognitive test perfor- mance of at-risk patients have been repeatedly described, although considerable inter-individual variability exists (Fusar-Poli et al., 2013). These impairments appear to progress during the development of first-episode psychosis: in the very early stages, defined by the presence of cognitive and perceptive basic symptoms (BS; Schultze-Lutter et al., 2007a) and the absence of attenuated (APS) and/or transient psychotic symptoms (BLIPS), cognitive impairments are less pronounced or ab- sent compared to later stages, in which APS and/or BLIPS of the UHR criteria are present (Pukrop et al., 2006, 2007; Frommann et al., 2011). Thus, in the early stage, two problems can occur with detecting emerg- ing cognitive impairments by neurocognitive tests: (1) an early slight decline in test performance might not be detectable when the score is still within the normal range according to the respective test norms, and (2) a deficit below the normal range might not be detected when a person is still able to cope adequately (e.g., by over-focusing). Thus, with regard to cognitive impairments, the early detection of psychosis resembles that of Alzheimer's dementia (AD; Knopman, 2012; Garcia-Ptacek et al., 2013). Mild cognitive impairments (MCI), as indicated by neurocognitive scores outside the normal range, are preceded by AD-related changes in the brain and by a subtle cognitive decline characterized by test performances that are still within the nor- mal range (Jessen et al., 2010). This subtle cognitive decline shows a temporal association with the occurrence of subjective cognitive Schizophrenia Research 154 (2014) 100–106 ⁎ Corresponding author at: University Hospital of Child and Adolescent Psychiatry and Psychotherapy, Bolligenstr. 111, Haus A, 3000 Bern 60, Switzerland. Tel.: +41 31 932 8564; fax: +41 31 932 8569. E-mail addresses: frauke.schultze-lutter@kjp.unibe.ch (F. Schultze-Lutter), joachim.klosterkoetter@uk-koeln.de (J. Klosterkötter), stephan.ruhrmann@uk-koeln.de (S. Ruhrmann). http://dx.doi.org/10.1016/j.schres.2014.02.010 0920-9964/© 2014 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Schizophrenia Research journal homepage: www.elsevier.com/locate/schres