Early-onset of symptoms predicts conversion to non-affective psychosis in ultra-high risk individuals

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Abstract

Objective

We examined if age of onset of psychiatric symptoms and/or sex predict conversion to non-affective or affective psychosis in individuals considered to be at ultra-high risk for schizophrenia.

Method

Participants (n = 86) were offered treatment and monthly follow-up until transition to psychosis, or for 12 months if they did not meet exit criteria for psychotic disorder. Individuals without transition to psychosis at 12-month were reassessed approximately 3 years after the end of the treatment phase. Ultra-high risk was defined by the presence of subthreshold and/or self-limiting psychotic symptoms and/or having a family history of psychotic disorder combined with functional decline. Cox regressions after adjustment for treatment interventions were applied to investigate associations between age of onset, sex, and other baseline measures with progression to psychotic outcomes.

Results

Early age of onset of psychiatric symptoms, in particular onset before age 18 was the only tested variable that significantly predicted non-affective psychosis. Independent significant predictors of affective psychosis were poor functioning, female sex and the presence of a combination of intake criteria (family history of psychosis plus drop in functioning, and attenuated and/or brief limited psychotic symptoms) at baseline.

Conclusions

Age of onset of psychiatric symptoms is the single most important factor associated with conversion to non-affective psychosis in ultra-high risk individuals.

Introduction

In the last decade there has been a dramatic increase in interest in the early manifestations of schizophrenia and other psychotic disorders, in particular, the prodromal stage of illness (Lieberman and Fenton, 2000). Because of the non-specific nature of these early manifestations and their limited predictive value for schizophrenia the term at-risk-mental-state has been suggested for the prepsychotic phase (McGorry and Singh, 1995). Several clinical risk definitions are currently under investigation including, the Personal Assessment and Crisis Evaluation (PACE) clinic's criteria that identify people putatively at high risk of developing psychosis through subthreshold and/or self-limiting psychotic symptoms and/or having a family history of psychotic disorder combined with functional decline (Yung et al., 1998). Klosterkötter et al. (2001) have utilized the concept of basic symptoms, subjectively experienced neuropsychological deficits in cognition, attention, perception and movement as factors related to risk for psychosis. Cornblatt et al. (2003) have adopted an approach which follows the neurodevelopmental model of schizophrenia proposing a subgroup with attenuated negative symptoms or attenuated disorganized symptoms, as earliest stage, succeeded by later stages with attenuated positive symptoms.

The certainty with which individuals can be identified who will develop psychosis in the near future is crucial for intervention studies in emerging psychosis. The PACE clinic criteria yielded a transition rate of 30–40% within 6–12 months (Yung et al., 1998); these criteria are therefore defining a group at ultra-high risk (UHR) for psychosis. In an attempt to further enhance the predictive accuracy in UHR patients Yung et al. (2004) examined measures of symptom duration, functioning, and psychopathology. Significant predictors of transition to psychosis included poor functioning, long duration of symptoms, high levels of depression and reduced attention, and family history of psychosis with decrease in functioning plus the experience of subthreshold psychotic symptoms. A combination of these predictive variables resulted in a model of psychosis prediction with good specificity and moderate sensitivity. However, predictor models derived from research environments are usually difficult to apply in everyday practice as application is limited by a lack of resources.

The epidemiological characteristics of a disorder can provide important clues in the search for etiology and are essential in the development of evidence based treatment models. Psychotic disorders are very rare below the age of 14 but show a marked increase in prevalence between the ages of 15 and 17 (Thomsen, 1996). Schizophrenia occurring in adolescence before the age of 18 has been defined as early-onset schizophrenia (Vourdas et al., 2003). Compared to individuals with adult-onset schizophrenia, an early onset of schizophrenia has been associated with more premorbid abnormalities (Hollis, 1995, Vourdas et al., 2003), higher levels of neurocognitive impairment (Hoff et al., 1996, Rhinewine et al., 2005), and poorer functional outcomes (Hollis, 2000). The findings in early-onset schizophrenia indicate that an onset of psychotic symptoms before the age of 18 years may represent a more severe variant of the adult form of the disorder (Hollis, 2000, Rhinewine et al., 2005). Based on these observations, at-risk-mental state with an onset of symptoms before the age of 18 might be associated with a worse outcome, namely a higher transition rate to psychosis and potentially schizophrenia.

Sex differences are also prominent in schizophrenia (Leung and Chue, 2000). Two systematic reviews found that the incidence of schizophrenia is significantly higher in men than in women (Aleman et al., 2003, McGrath et al., 2004). Males have an earlier age of onset in schizophrenia (Angermeyer and Kuhn, 1988) and less favorable short to medium term outcomes (Angermeyer et al., 1990, Leung and Chue, 2000). However, it is unclear if at-risk-mental-state in males is associated with a higher risk of progression to schizophrenia than in females.

The present study examined if age of onset of psychiatric symptoms and/or sex effect conversion to full diagnostic threshold psychotic disorder in UHR individuals. We hypothesized that (a) younger age of onset, in particular, an onset of symptoms before the 18th birthday, and (b) male gender are associated with a significantly higher risk of transition to non-affective psychotic disorder.

Section snippets

Patients

Patients were recruited to the PACE clinic in Melbourne, Australia, to participate in a randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in UHR young people (Yung et al., 1998, McGorry et al., 2002). The PACE clinic functions as part of ORYGEN Youth Health, a specialist mental health service for young people. The present study was approved by the research and ethics committee of North-Western Mental Health (Melbourne, Australia).

Results

522 referrals were screened for inclusion criteria between October 1996 and February 1999. One hundred and thirty-five (25.9%) of 522 met UHR criteria, of those, 68.1% (92 of 135) agreed to research involvement. Four individuals missed all appointments and two committed suicide after the initial assessment phase. The study sample is therefore comprised of 86 individuals (mean age = 19.74 years, S.D. = 3.65, range = 14–28, median = 20.0) with longitudinal information.

Discussion

Symptoms and behaviors of the prodromal phase overlap with mental experiences of people who do not develop schizophrenia or other psychotic disorders. The knowledge of factors specifically associated with conversion to different psychotic outcomes may assist and guide early detection and intervention. Age of onset has been proposed as the single most important clue to the etiology of schizophrenia (Delisi, 1992). Our results support this view. Among selected potential predictors, we found

Acknowledgements

The Personal Assistance and Crisis Evaluation (PACE) clinic was supported by the Victorian Health Promotion Foundation, Melbourne; National Health and Medical Research Council, Canberra, Australia; Australian Research and Development Grants Advisory Scheme, Canberra; National Alliance for Schizophrenia and Depression, Great Neck, NY; Stanley Foundation, Muscatine, Iowa; and Janssen-Cilag Australia, Sydney.

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