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Early detection and intervention strategies in patients at clinical high-risk (CHR) for syndromal psychosis have the potential to contain the morbidity of schizophrenia and similar conditions. However, research criteria that have relied on severity and number of positive symptoms are limited in their specificity and risk high false-positive rates. Our objective was to examine the degree to which measures of recency of onset or intensification of positive symptoms [a.k.a., new or worsening (NOW) symptoms] contribute to predictive capacity.
We recruited 109 help-seeking individuals whose symptoms met criteria for the Progression Subtype of the Attenuated Positive Symptom Psychosis-Risk Syndrome defined by the Structured Interview for Psychosis-Risk Syndromes and followed every three months for two years or onset of syndromal psychosis.
Forty-one (40.6%) of 101 participants meeting CHR criteria developed a syndromal psychotic disorder [mostly (80.5%) schizophrenia] with half converting within 142 days (interquartile range: 69–410 days). Patients with more NOW symptoms were more likely to convert (converters: 3.63 ± 0.89; non-converters: 2.90 ± 1.27; p = 0.001). Patients with stable attenuated positive symptoms were less likely to convert than those with NOW symptoms. New, but not worsening, symptoms, in isolation, also predicted conversion.
Results suggest that the severity and number of attenuated positive symptoms are less predictive of conversion to syndromal psychosis than the timing of their emergence and intensification. These findings also suggest that the earliest phase of psychotic illness involves a rapid, dynamic process, beginning before the syndromal first episode, with potentially substantial implications for CHR research and understanding the neurobiology of psychosis.
The authors developed a practical and clinically useful model to predict the risk of psychosis that utilizes clinical characteristics empirically demonstrated to be strong predictors of conversion to psychosis in clinical high-risk (CHR) individuals. The model is based upon the Structured Interview for Psychosis Risk Syndromes (SIPS) and accompanying clinical interview, and yields scores indicating one's risk of conversion.
Baseline data, including demographic and clinical characteristics measured by the SIPS, were obtained on 199 CHR individuals seeking evaluation in the early detection and intervention for mental disorders program at the New York State Psychiatric Institute at Columbia University Medical Center. Each patient was followed for up to 2 years or until they developed a syndromal DSM-4 disorder. A LASSO logistic fitting procedure was used to construct a model for conversion specifically to a psychotic disorder.
At 2 years, 64 patients (32.2%) converted to a psychotic disorder. The top five variables with relatively large standardized effect sizes included SIPS subscales of visual perceptual abnormalities, dysphoric mood, unusual thought content, disorganized communication, and violent ideation. The concordance index (c-index) was 0.73, indicating a moderately strong ability to discriminate between converters and non-converters.
The prediction model performed well in classifying converters and non-converters and revealed SIPS measures that are relatively strong predictors of conversion, comparable with the risk calculator published by NAPLS (c-index = 0.71), but requiring only a structured clinical interview. Future work will seek to externally validate the model and enhance its performance with the incorporation of relevant biomarkers.
DSM-5 proposes an Attenuated Psychosis Syndrome (APS) for further investigation, based upon the Attenuated Positive Symptom Syndrome (APSS) in the Structured Interview for Psychosis-Risk Syndromes (SIPS). SIPS Unusual Thought Content, Disorganized Communication and Total Disorganization scores predicted progression to psychosis in a 2015 NAPLS-2 Consortium report. We sought to independently replicate this in a large single-site high-risk cohort, and identify baseline demographic and clinical predictors beyond current APS/APSS criteria.
We prospectively studied 200 participants meeting criteria for both the SIPS APSS and DSM-5 APS. SIPS scores, demographics, family history of psychosis, DSM Axis-I diagnoses, schizotypy, and social and role functioning were assessed at baseline, with follow-up every 3 months for 2 years.
The conversion rate was 30% (n = 60), or 37.7% excluding participants who were followed under 2 years. This rate was stable across time. Conversion time averaged 7.97 months for 60% who developed schizophrenia and 15.68 for other psychoses. Mean conversion age was 20.3 for males and 23.5 for females. Attenuated odd ideas and thought disorder appear to be the positive symptoms which best predict psychosis in a logistic regression. Total negative symptom score, Asian/Pacific Islander and Black/African-American race were also predictive. As no Axis-I diagnosis or schizotypy predicted conversion, the APS is supported as a distinct syndrome. In addition, cannabis use disorder did not increase risk of conversion to psychosis.
NAPLS SIPS findings were replicated while controlling for clinical and demographic factors, strongly supporting the validity of the SIPS APSS and DSM-5 APS diagnosis.
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