‘At-risk’ for psychosis research: where are we heading?

Abstract

The 'at-risk' criteria are a useful paradigm for investigating the psychological, neurocognitive, neurobiological and genetic risk factors for psychosis, specifically schizophrenia. To date, the primary outcome of interest in at-risk research has been the development of psychotic disorder, whereby patients are categorized as either having 'transitioned' or 'not transitioned'. Despite the acceptance of this dichotomy, it is important to consider that the threshold at which psychotic symptoms progress from attenuated to frank 'psychotic disorder' is arbitrary and may be incorrect or meaningless in terms of neurobiological and functional changes associated with psychosis. This has implications for clinical care and the search for markers of schizophrenia. We present recent research suggesting that the term 'outcome' needs to be broadened to incorporate non-psychotic diagnoses, functioning and negative symptoms. Shifting the traditional notion of outcome is the future challenge for at-risk research, but the inclusion of outcomes other than psychosis is likely to result in better aetiological models of psychotic illness.

Specificity of childhood psychotic symptoms for predicting schizophrenia by 38 years of age: a birth cohort study

“…This is in keeping with other recent studies (Kelleher et al 2012b;Werbeloff et al 2012) and commentaries (Lin et al 2012;, which also suggest that it may no longer be useful to extrapolate findings based on early psychotic symptoms solely to psychotic disorders, as it can no longer be assumed that individuals with these symptoms will eventually develop a psychotic disorder. Indeed, the lack of specificity of these early psychotic symptoms should not be that surprising because in childhood they co-occur with other mental health problems (including self-harm; Polanczyk et al 2010) and both prodromal (Kelleher et al 2012d) and clinical schizophrenia (Murray et al 2003;Weich et al 2011) have high rates of co-morbidity.…”

“…cognitive behavioral therapy; Maddox et al 2012) to improve their general psychological well-being and arm them with suitable coping strategies to tackle the challenges of adolescence. Clinical trials are required to test this proposition with affected children and such research should assess a broad range of potential mental health outcomes (Lin et al 2012). …”

Misattributing speech and jumping to conclusions: A longitudinal study in people at high risk of psychosis

“…Nevertheless, as in previous studies [11], the sample was heterogenous with respect to clinical and functional outcomes: 22% of subjects developed psychosis during follow-up, whereas 39% made a ''functional recovery'', as indexed by a follow-up GAF score > 75. Interestingly functional status at follow-up was unrelated to whether full-blown psychosis had occurred during the follow-up period, supporting suggestions that measures of ''outcome'' in this group be broadened beyond just transition to psychosis [22].…”

Functional Outcome in People at High Risk for Psychosis Predicted by Thalamic Glutamate Levels and Prefronto-Striatal Activation

“…However, the threshold at which psychotic symptoms are regarded as diagnostic of a psychotic disorder, rather than a highrisk state, does not always reflect the level of functioning in UHR cases. 6 Furthermore, around 70% of UHR individuals will not develop psychosis, 7 despite many of this subgroup having poor functional outcomes and requiring long-term clinical care. 8 Poor functional outcomes in UHR cohorts have recently been associated with a long duration of high-risk symptoms before presentation 9 and poor neurocognitive performance, 10 especially on tasks of verbal memory and fluency.…”