Validity of the Prodromal Risk Syndrome for First Psychosis: Findings From the North American Prodrome Longitudinal Study

Treatment and prevention studies over the past decade have enrolled patients believed to be at risk for future psychosis. These patients were considered at risk for psychosis by virtue of meeting research criteria derived from retrospective accounts of the psychosis prodrome. This study evaluated the diagnostic validity of the prospective “prodromal risk syndrome” construct. Patients assessed by the Structured Interview for Prodromal Syndromes as meeting criteria of prodromal syndromes (n = 377) from the North American Prodrome Longitudinal Study were compared with normal comparison (NC, n = 196), help-seeking comparison (HSC, n = 198), familial high-risk (FHR, n = 40), and schizotypal personality disorder (SPD, n = 49) groups. Comparisons were made on variables from cross-sectional demographic, symptom, functional, comorbid diagnostic, and family history domains of assessment as well as on follow-up outcome. Prodromal risk syndrome patients as a group were robustly distinguished from NC subjects across all domains and distinguished from HSC subjects and from FHR subjects on most measures in many of these domains. Adolescent and young adult SPD patients, while distinct from prodromal patients on definitional grounds, were similar to prodromals on multiple measures, consistent with SPD in young patients possibly being an independent risk syndrome for psychosis. The strong evidence of diagnostic validity for the prodromal risk syndrome for first psychosis raises the question of its evaluation for inclusion in Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition).     

The phenomenological critique and self-disturbance: implications for ultra-high risk ("prodrome") research

Recent years have witnessed widespread interest in the early phase of schizophrenia and other psychotic disorders. Strategies have been introduced to attempt to identify individuals in the prepsychotic or prodromal phase. The most widely used of these approaches is the ultra-high risk (UHR) approach, which combines known trait and state risk factors for psychotic disorder. However, researchers guided by phenomenological theory have argued that modern psychiatry's neglect of subjective experience has compromised researchers' understanding of psychotic disorder and has thereby limited efforts at prospective and early identification. Phenomenological research indicates that disturbance of the basic sense of self may be a core marker of psychotic vulnerability, particularly of schizophrenia spectrum disorders. It is argued that identifying self-disturbance in the UHR population may provide a means of further "closing in" on individuals truly at high risk of psychotic disorder, thus supplementing the UHR identification approach. This would be of practical value in the sense of reducing inclusion of "false-positive" cases in UHR samples and of theoretical value in the sense of shedding light on core features of psychotic pathology. The strong explanatory power and empirical findings to date invite further research into the role of self-disturbance as a phenotypic vulnerability marker for psychotic disorder.     

A randomized trial of family focused treatment for adolescents and young adults at risk for psychosis: study rationale, design and methods

Aim: This article outlines the rationale for a family‐focused psychoeducational intervention for individuals at risk for psychosis and explains the design of a randomized multisite trial to test its efficacy. Methods: Adolescents and young adults that meet criteria for a psychosis risk syndrome at eight participating North American Prodromal Longitudinal Study sites are randomly assigned to a 6‐month, 18‐session family‐focused treatment for prodromal youth or a 3‐session psychoeducational enhanced care control intervention and followed over 1 year. Results: The results will determine whether the use of a family intervention is able to significantly improve functional outcomes, decrease the severity of positive symptoms and possibly prevent the onset of full psychosis, compared with enhanced care alone. Levels of familial criticism at baseline are hypothesized to moderate responses to family intervention. Improvements in knowledge about symptoms, family communication and problem solving will be tested as mediators in the pathways between treatment assignment and clinical or psychosocial outcomes in high‐risk youth. Conclusions: The ongoing trial evaluates whether a non‐invasive psychosocial approach can significantly enhance functional outcomes and prevent the ultra high risk patients from developing psychosis. The results will provide an important stepping stone in the movement of the field from refining early detection strategies to developing efficacious preventative treatments.     

Experience of trauma and conversion to psychosis in an ultra‐high‐risk (prodromal) group

Bechdolf A, Thompson A, Nelson B, Cotton S, Simmons MB, Amminger GP, Leicester S, Francey SM, McNab C, Krstev H, Sidis A, McGorry PD, Yung AR. Experience of trauma and conversion to psychosis in an ultra‐high‐risk (prodromal) group. Objective: We aimed to replicate a recent finding of high prevalence of trauma history in patients at ‘ultra‐high risk’ (UHR) of psychotic disorder and to investigate whether trauma predicts conversion to psychosis in this population. Method: A consecutive sample of UHR patients was assessed. History of trauma was accessed with the General Trauma Questionnaire. Cox regression models were used to explore relationship between conversion to psychosis and trauma. Results: Of 92 UHR patients nearly 70% had experienced a traumatic event and 21.7% developed psychosis during follow‐up (mean 615 days). Patients who had experienced a sexual trauma (36%) were significantly more likely to convert to first‐episode psychosis (OR 2.96) after controlling for meeting multiple UHR intake groups. Conclusion: UHR patients have a high prevalence of history of trauma. Previous sexual trauma may be a predictor of onset of psychotic disorder in this population.     

Prodromal psychosis screening in adolescent psychiatry clinics

Background: Research has identified a syndrome conferring ultra‐high risk (UHR) for psychosis, although UHR interviews require intensive staff training, time and patient burden. Previously, we developed the Prodromal Questionnaire (PQ) to screen more efficiently for UHR syndromes. Aims: This study examined the concurrent validity of the PQ against UHR status and preliminary predictive validity for later psychotic disorder. Method: We assessed a consecutive patient sample of 408 adolescents who presented to psychiatry clinics in Helsinki, Finland, seeking mental health treatment, including 80 participants who completed the Structured Interview for Prodromal Syndromes (SIPS). Results: A cut‐off score of 18 or more positive symptoms on the PQ predicted UHR diagnoses on the SIPS with 82% sensitivity and 49% specificity. Three of 14 (21%) participants with high PQ scores and SIPS UHR diagnoses developed full psychotic disorders within 1 year. Conclusions: Using the PQ and SIPS together can be an efficient two‐stage screening process for prodromal psychosis in mental health clinics.     

Help-seeking pathways in early psychosis

Introduction Understanding the help-seeking pathways of patients with a putative risk of developing psychosis helps improving development of specialised care services. This study aimed at obtaining information about: type of health professionals contacted by patients at putative risk for psychosis on their help-seeking pathways; number of contacts; type of symptoms leading to contacts with health professionals; interval between initial contact and referral to a specialised outpatient service. Method The help-seeking pathways were assessed as part of a prospective study in 104 patients with suspected at-risk states for psychosis. Results The mean number of contacts prior to referral was 2.38. Patients with psychotic symptoms more often contacted mental health professionals, whereas patients with insidious and more unspecific features more frequently contacted general practitioners (GPs). Conclusions GPs have been found to under-identify the insidious features of emerging psychosis (Simon et al. (2005) Br J Psychiatry 187:274–281). The fact that they were most often contacted by patients with exactly these features calls for focussed and specialised help for primary care physicians. Thus, delays along the help-seeking pathways may be shortened. This may be of particular relevance for patients with the deficit syndrome of schizophrenia.     

Early signs and symptoms of psychosis among Palauan adolescents

Aim: This study was designed to identify early symptoms associated with the occurrence of psychosis during adolescence. Method: Participants were recruited in the Republic of Palau, an isolated island nation in Micronesia with a prevalence rate for schizophrenia of 1.99%. Diagnostic interviews were used to obtain reports of early and current symptoms from 112 genetically high-risk (GHR) and 208 genetically low-risk (GLR) adolescents (ages 16–23). Based on current psychotic symptoms, participants were sorted into three groups: non-clinical, at-risk/symptomatic risk and clinically symptomatic. Results: Multivariate analysis of variance revealed several between-group differences on rates of early symptoms. Most notably, youth who were in the GHR-clinically symptomatic group reported significantly higher rates of early marijuana use than GLR-clinically symptomatic youth, who were significantly more likely to report early symptoms of depression and behaviour disorders. In addition, several gender based differences in the link between early symptoms and adolescent onset psychosis were noted. Conclusions: Findings are generally consistent with previous research on early indicators, though several unexpected findings suggest that results from this study may not be fully generalizable beyond this relatively isolated and culturally distinct Micronesian nation.     

Recovery from an at-risk state: clinical and functional outcomes of putatively prodromal youth who do not develop psychosis

Background: The "clinical high risk" (CHR) construct was developed to identify individuals at imminent risk of developing psychosis. However, most individuals identified as CHR do not convert to psychosis, and it is unknown whether these nonconverting individuals actually recover from an at-risk state. Methods: Eighty-four prospectively identified patients meeting CHR criteria, and 58 healthy comparison subjects were followed in a 2-year longitudinal study. Analyses examined rates of conversion, clinical, and functional recovery. Proportional cause-specific hazard models were used to examine the effects of baseline and time-varying predictors on conversion and remission. Trajectories of symptoms and psychosocial functioning measures were compared across outcome groups. Results: Competing risk survival analyses estimated that 30% of CHR subjects convert to psychosis by 2 years, while 36% symptomatically remit and 30% functionally recover by 2 years. Lower levels of negative and mood/anxiety symptoms were related to increased likelihood of both symptomatic and functional recovery. CHR subjects who remitted symptomatically were more similar to healthy controls in terms of both their baseline and longitudinal symptoms and functioning than the other outcome groups. Conclusions: Nonconverting CHR cases represented a heterogeneous group. Given that nonconverted subjects who remitted symptomatically also presented initially with less severe prodromal symptomatology and showed a distinct normative trajectory of both symptoms and psychosocial functioning over time, it may be possible to refine the CHR criteria to reduce the number of "false positive" cases by eliminating those who present with less severe attenuated positive symptoms or show early improvements in terms of symptoms or functioning.     

When things are not as they seem: detecting first‐episode psychosis upon referral to ultra high risk (‘prodromal’) clinics

The current paper examines a neglected function of ‘ultra high risk’ (UHR) clinics: to detect first‐episode psychosis (FEP) mistakenly identified as a prodrome. A clinical audit was conducted of referrals to a UHR service, the Personal Assessment and Crisis Evaluation Clinic, over a 12‐month period (April 2005–March 2006). In this audit, 11.4% of the total number of referrals (n= 149) and 11.9% of those who attended a first appointment were psychotic on referral. These figures indicate that a substantial proportion of individuals thought to be prodromal are in fact suffering FEP. UHR clinics minimize duration of untreated psychosis for FEP patients mistaken as prodromal.     

Generalized and specific cognitive performance in clinical high-risk cohorts: a review highlighting potential vulnerability markers for psychosis

Cognitive deficits are a core feature of established psychotic illnesses. However, the association between cognition and emerging psychosis is less understood. While there is some evidence that cognitive deficits are present prior to the onset of psychosis, findings are not consistent. In this article we provide an overview of the more general cognitive findings available from genetic high-risk studies, retrospective studies, and birth cohort studies. We then focus the review on neuropsychological performance in clinically "at-risk" groups. Overall, general cognitive ability as assessed by established batteries appears to remain relatively intact in these ultra-high risk cohorts and is a poor predictor close to illness onset relative to other vulnerability factors. Further decline may occur with illness progression, more consistent with state relative to trait factors. In addition, most established cognitive tasks involve several relatively discrete cognitive subprocesses, where findings from general batteries of subtests may mask specific deficits. In this context, our review suggests that relatively specific olfactory identification and spatial working memory deficits exist prior to illness onset and may be more potent trait markers for psychosis than cognitively dense tasks such as verbal memory. Suggestions for further research address the importance of standardization of inclusion criteria and the maintenance of basic neuropsychological assessment to allow better comparison of findings across centers. Further, in order to better understand the aetiopathology of cognitive dysfunction in psychosis, more experimental, hypothesis-driven measures of discrete cognitive processes are required. Delineation of the relationship between specific cognitive ability and symptoms from data-driven approaches may improve our understanding of the role of cognition during psychosis onset.