At Clinical High Risk for Psychosis: Outcome for Nonconverters

Harvard University, Cambridge, Massachusetts, United States
American Journal of Psychiatry (Impact Factor: 12.3). 04/2011; 168(8):800-5. DOI: 10.1176/appi.ajp.2011.10081191
Source: PubMed


A major focus of early intervention research is determining the risk of conversion to psychosis and developing optimal algorithms of prediction. Although reported rates of nonconversion vary in the literature, the nonconversion rate always encompasses a majority (50%-85%) of the sample participants. Less is known about the outcome among this group, referred to as false positive individuals.
A longitudinal study was conducted of more than 300 prospectively identified treatment-seeking individuals meeting criteria for a psychosis-risk syndrome. Participants were recruited and evaluated across eight clinical research centers as part of the North American Prodrome Longitudinal Study. Over a 2.5-year follow-up assessment period, 214 (71%) participants had not made the transition to psychosis.
The sample examined included 111 individuals who had at least 1 year of follow-up data available and did not transition to psychosis within the study duration. In year 1, there was significant improvement in ratings for attenuated positive and negative symptoms. However, at least one attenuated positive symptom was still present for 43% of the sample at 1 year and for 41% at 2 years. At the follow-up timepoints, social and role functioning were significantly poorer in the clinical sample relative to nonpsychiatric comparison subjects.
Help-seeking individuals who meet prodromal criteria appear to represent those who are truly at risk for psychosis and are showing the first signs of illness, those who remit in terms of the symptoms used to index clinical high-risk status, and those who continue to have attenuated positive symptoms.

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    • "The current study aimed to expand upon previous research by examining, in a large cohort of individuals at CHR for psychosis and healthy controls, whether social cognition is impaired. It has been observed that the majority of individuals who present as being at CHR and who do not make the transition to psychosis continue to have deficits in social function (Addington et al., 2011), plus there is a link between social cognition and social functioning . It would therefore be important to have an improved understanding of these early deficits in social cognition in the CHR population as a whole so that potential treatments at this pre-psychotic phase could be developed. "
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    ABSTRACT: Social cognition, the mental operations that underlie social interactions, is a major construct to investigate in schizophrenia. Impairments in social cognition are present before the onset of psychosis, and even in unaffected first-degree relatives, suggesting that social cognition may be a trait marker of the illness. In a large cohort of individuals at clinical high risk for psychosis (CHR) and healthy controls, three domains of social cognition (theory of mind, facial emotion recognition and social perception) were assessed to clarify which domains are impaired in this population. Six-hundred and seventy-five CHR individuals and 264 controls, who were part of the multi-site North American Prodromal Longitudinal Study, completed The Awareness of Social Inference Test, the Penn Emotion Recognition task, the Penn Emotion Differentiation task, and the Relationship Across Domains, measures of theory of mind, facial emotion recognition, and social perception, respectively. Social cognition was not related to positive and negative symptom severity, but was associated with age and IQ. CHR individuals demonstrated poorer performance on all measures of social cognition. However, after controlling for age and IQ, the group differences remained significant for measures of theory of mind and social perception, but not for facial emotion recognition. Theory of mind and social perception are impaired in individuals at CHR for psychosis. Age and IQ seem to play an important role in the arising of deficits in facial affect recognition. Future studies should examine the stability of social cognition deficits over time and their role, if any, in the development of psychosis.
    Schizophrenia Research 12/2015; in press. DOI:10.1016/j.scog.2015.04.004 · 3.92 Impact Factor
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    • "However, the majority of UHR patients do not develop psychotic disorder even up to 10 years post-identification (Nelson et al. 2013). Nonetheless, many remain symptomatic and disabled (Addington et al. 2011; Schlosser et al. 2012; Lin et al. 2015b). It is important therefore to study psychosocial functioning as an outcome in at-risk research (Yung et al. 2010; Lin et al. 2013b). "
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    ABSTRACT: Individuals identified as at ultra-high risk (UHR) for psychosis are at risk of poor functional outcome regardless of development of psychotic disorder. Studies examining longitudinal predictors of poor functioning have tended to be small and report only medium-term follow-up data. We sought to examine clinical predictors of functional outcome in a long-term longitudinal study. Participants were 268 (152 females, 116 males) individuals identified as UHR 2-14 years previously. A range of clinical and sociodemographic variables were assessed at baseline. Functioning at follow-up was assessed using the Social and Occupational Functioning Assessment Scale (SOFAS). Baseline negative symptoms, impaired emotional functioning, disorders of thought content, low functioning, past substance use disorder and history of childhood maltreatment predicted poor functioning at follow-up in univariate analyses. Only childhood maltreatment remained significant in the multivariate analysis (p < 0.001). Transition to psychosis was also significantly associated with poor functioning at long-term follow-up [mean SOFAS score 59.12 (s.d. = 18.54) in the transitioned group compared to 70.89 (s.d. = 14.00) in the non-transitioned group, p < 0.001]. Childhood maltreatment was a significant predictor of poor functioning in both the transitioned and non-transitioned groups. Childhood maltreatment and transition to psychotic disorder independently predicted poor long-term functioning. This suggests that it is important to assess history of childhood maltreatment in clinical management of UHR individuals. The finding that transition to psychosis predicts poor long-term functioning strengthens the evidence that the UHR criteria detect a subgroup at risk for schizophrenia.
    Psychological Medicine 07/2015; DOI:10.1017/S003329171500135X · 5.94 Impact Factor
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    • "First, the follow-up assessment was limited to a relatively short period of 2 years. Although significant improvement in symptoms and functioning reportedly occurs typically within 1 year (Addington et al., 2011; Velthorst et al., 2011), changes in symptomatic and functional status are still possible, as is psychotic transition, after 2 years in CHR non-converters. Second, the follow-up duration varied among individual CHR subjects. "
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    ABSTRACT: The aim of this study was to investigate whether P300 could predict the short-term prognosis of subjects at clinical high risk (CHR) for psychosis who do not convert to psychotic disorder (non-converters). CHR subjects were examined with auditory P300 at baseline, and their clinical state was regularly assessed up to 2years. 45 CHR non-converters were divided into remitter and non-remitter groups. Repeated-measures analysis of variance (ANOVA) was performed to compare baseline P300 between the two groups. Multiple regression analysis was used to identify factors predicting symptomatic or functional improvement in CHR subjects during the follow-up period. There were no group differences in P300 amplitude or latency between CHR remitters and non-remitters. In the multiple regression analysis, P300 amplitude at Pz (β=0.206, 95% confidence interval [95CI]=0.035 to 0.567, p=0.028) significantly predicted later amelioration of the Scale of Prodromal Symptoms (SOPS) negative symptoms. Improvement in SOPS general symptoms was significantly predicted by P300 amplitude at Pz (β=0.255, 95CI=0.065 to 0.455, p=0.010) and mood stabilizer use (β=0.199, 95CI=0.081 to 4.154, p=0.042). These results indicate that P300 may be a possible predictor of improvement in negative and general symptoms in CHR non-converters. Our findings support the recommendation that a broader concept of assessment guidelines is needed to forecast clinical outcome and provide appropriate interventions for CHR non-converters. Copyright © 2015 Elsevier B.V. All rights reserved.
    Schizophrenia Research 05/2015; 165(2-3). DOI:10.1016/j.schres.2015.04.033 · 3.92 Impact Factor
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