Adolescents and adults at clinical high-risk for psychosis: age-related differences in attenuated positive symptoms syndrome prevalence and entanglement with basic symptoms.

BACKGROUND: The attenuated positive symptoms syndrome (APSS) is considered an at-risk indicator for psychosis. However, the characteristics and developmental aspects of the combined or enriched risk criteria of APSS and basic symptom (BS) criteria, including self-experienced cognitive disturbances (COGDIS) remain under-researched. METHOD: Based on the Structured Interview of Prodromal Syndromes (SIPS), the prevalence of APSS in 13- to 35-year-old individuals seeking help in an early recognition program for schizophrenia and bipolar-spectrum disorders was examined. BS criteria and COGDIS were rated using the Schizophrenia Proneness Instrument for Adults/Children and Youth. Participants meeting APSS criteria were compared with participants meeting only BS criteria across multiple characteristics. Co-occurrence (APSS+/BS+, APSS+/COGDIS+) was compared across 13-17, 18-22 and 23-35 years age groups. RESULTS: Of 175 individuals (age = 20.6 ± 5.8, female = 38.3%), 94 (53.7%) met APSS criteria. Compared to BS, APSS status was associated with suicidality, higher illness severity, lower functioning, higher SIPS positive, negative, disorganized and general symptoms scores, depression scores and younger age (18.3 ± 5.0 v. 23.2 ± 5.6 years, p < 0.0001) with age-related differences in the prevalence of APSS (ranging from 80.3% in 13- to 17-year-olds to 33.3% in 23- to 35-year-olds (odds ratio 0.21, 95% confidence interval 0.11-0.37). Within APSS+ individuals, fewer adolescents fulfilled combined risk criteria of APSS+/BS+ or APSS+/COGDIS+ compared to the older age groups. CONCLUSIONS: APSS status was associated with greater suicidality and illness/psychophathology severity in this help-seeking cohort, emphasizing the need for clinical care. The age-related differences in the prevalence of APSS and the increasing proportion of APSS+/COGDIS+ may point to a higher proportion of non-specific/transient, rather than risk-specific attenuated positive symptoms in adolescents.

Changes in neurocognitive functioning during transition to manifest disease: comparison of individuals at risk for schizophrenic and bipolar affective psychoses.

BACKGROUND: Neurocognitive deficits are important aspects of schizophrenic disorder because they have a strong impact on social and vocational outcomes. Previously it was assumed that cognitive abilities progressively deteriorate with illness onset. However, recent research results have contradicted this with observations of continuous or even improved performance in individuals at risk for psychosis or manifest schizophrenia. The objective of our longitudinal study was to examine neurocognitive functioning in help-seeking individuals meeting basic symptoms or ultra-high-risk criteria for schizophrenic psychosis (HRSchiz) or risk criteria for affective psychosis (HRBip). The progression of cognitive functioning in individuals converting to psychosis was compared with that of at-risk individuals who did not convert during the follow-up period. METHOD: Data were available from 86 study participants who completed neurocognitive and clinical assessments at baseline and, on average, 12.8 (s.d. = 1.5) months later. Neurocognitive measures were grouped according to their load in factor analysis to five cognitive domains: speed, attention, fluency, learning and memory, and working memory. RESULTS: Neurocognitive functioning in HRSchiz and HRBip individuals generally improved over time. Subjects converting to manifest psychosis displayed a stable neurocognitive profile from baseline to follow-up. Compared with non-converters, they had already demonstrated a significantly lower level of performance during their baseline examinations. CONCLUSIONS: Our data provide no evidence for a progressive cognitive decline in individuals at risk of psychosis. In line with the neurodevelopmental model, our findings suggest that cognitive deficits are already present very early, before or during the prodromal stage of the illness.

Neurocognitive profiles in help-seeking individuals: comparison of risk for psychosis and bipolar disorder criteria.

BACKGROUND: Neurocognitive deficits are important aspects of the schizophrenic disorders because they have a strong impact on social and vocational outcomes. We expanded on previous research by focusing on the neurocognitive profiles of persons at high risk (HR) or ultra-high risk (UHR) for schizophrenic and affective psychoses. Our main aim was to determine whether neurocognitive measures are sufficiently sensitive to predict a group affiliation based on deficits in functional domains. METHOD: This study included 207 help-seeking individuals identified as HR (n = 75), UHR (n = 102) or at high risk for bipolar disorder (HRBip; n = 30), who were compared with persons comprising a matched, healthy control group (CG; n = 50). Neuropsychological variables were sorted according to their load in a factor analysis and were compared among groups. In addition, the likelihood of group membership was estimated using logistic regression analyses. RESULTS: The performance of HR and HRBip participants was comparable, and intermediate between the controls and UHR. The domain of processing speed was most sensitive in discriminating HR and UHR [odds ratio (OR) 0.48, 95% confidence interval (CI) 0.28-0.78, p = 0.004] whereas learning and memory deficits predicted a conversion to schizophrenic psychosis (OR 0.47, 95% CI 0.25-0.87, p = 0.01). CONCLUSIONS: Performances on neurocognitive tests differed among our three at-risk groups and may therefore be useful in predicting psychosis. Overall, cognition had a profound effect on the extent of general functioning and satisfaction with life for subjects at risk of psychosis. Thus, this factor should become a treatment target in itself.

Checking the predictive accuracy of basic symptoms against ultra high-risk criteria and testing of a multivariable prediction model: Evidence from a prospective three-year observational study of persons at clinical high-risk for psychosis.

BACKGROUND: The aim of this study was to critically examine the prognostic validity of various clinical high-risk (CHR) criteria alone and in combination with additional clinical characteristics. METHODS: A total of 188 CHR positive persons from the region of Zurich, Switzerland (mean age 20.5 years; 60.2% male), meeting ultra high-risk (UHR) and/or basic symptoms (BS) criteria, were followed over three years. The test battery included the Structured Interview for Prodromal Syndromes (SIPS), verbal IQ and many other screening tools. Conversion to psychosis was defined according to ICD-10 criteria for schizophrenia (F20) or brief psychotic disorder (F23). RESULTS: Altogether n=24 persons developed manifest psychosis within three years and according to Kaplan-Meier survival analysis, the projected conversion rate was 17.5%. The predictive accuracy of UHR was statistically significant but poor (area under the curve [AUC]=0.65, P<.05), whereas BS did not predict psychosis beyond mere chance (AUC=0.52, P=.730). Sensitivity and specificity were 0.83 and 0.47 for UHR, and 0.96 and 0.09 for BS. UHR plus BS achieved an AUC=0.66, with sensitivity and specificity of 0.75 and 0.56. In comparison, baseline antipsychotic medication yielded a predictive accuracy of AUC=0.62 (sensitivity=0.42; specificity=0.82). A multivariable prediction model comprising continuous measures of positive symptoms and verbal IQ achieved a substantially improved prognostic accuracy (AUC=0.85; sensitivity=0.86; specificity=0.85; positive predictive value=0.54; negative predictive value=0.97). CONCLUSIONS: We showed that BS have no predictive accuracy beyond chance, while UHR criteria poorly predict conversion to psychosis. Combining BS with UHR criteria did not improve the predictive accuracy of UHR alone. In contrast, dimensional measures of both positive symptoms and verbal IQ showed excellent prognostic validity. A critical re-thinking of binary at-risk criteria is necessary in order to improve the prognosis of psychotic disorders.