Latent class cluster analysis of symptom ratings identifies distinct subgroups within the clinical high risk for psychosis syndrome

© 2017 The clinical-high-risk for psychosis (CHR-P) syndrome is heterogeneous in terms of clinical presentation and outcomes. Identifying more homogenous subtypes of the syndrome may help clarify its etiology and improve the prediction of psychotic illness. This study applied latent class cluster analysis (LCCA) to symptom ratings from the North American Prodrome Longitudinal Studies 1 and 2 (NAPLS 1 and 2). These analyses produced evidence for three to five subgroups within the CHR-P syndrome. Differences in negative and disorganized symptoms distinguished among the subgroups. Subgroup membership was found to predict conversion to psychosis. The authors contrast the methods employed within this study with previous attempts to identify more homogenous subgroups of CHR-P individuals and discuss how these results could be tested in future samples of CHR-P individuals

Networks of blood proteins in the neuroimmunology of schizophrenia.

Levels of certain circulating cytokines and related immune system molecules are consistently altered in schizophrenia and related disorders. In addition to absolute analyte levels, we sought analytes in correlation networks that could be prognostic. We analyzed baseline blood plasma samples with a Luminex platform from 72 subjects meeting criteria for a psychosis clinical high-risk syndrome; 32 subjects converted to a diagnosis of psychotic disorder within two years while 40 other subjects did not. Another comparison group included 35 unaffected subjects. Assays of 141 analytes passed early quality control. We then used an unweighted co-expression network analysis to identify highly correlated modules in each group. Overall, there was a striking loss of network complexity going from unaffected subjects to nonconverters and thence to converters (applying standard, graph-theoretic metrics). Graph differences were largely driven by proteins regulating tissue remodeling (e.g. blood-brain barrier). In more detail, certain sets of antithetical proteins were highly correlated in unaffected subjects (e.g. SERPINE1 vs MMP9), as expected in homeostasis. However, for particular protein pairs this trend was reversed in converters (e.g. SERPINE1 vs TIMP1, being synthetical inhibitors of remodeling of extracellular matrix and vasculature). Thus, some correlation signals strongly predict impending conversion to a psychotic disorder and directly suggest pharmaceutical targets

Psychotropic medication use in youth at high risk for psychosis: Comparison of baseline data from two research cohorts 1998-2005 and 2008-2011

Background: Antipsychotic medication use rates have generally been rising among youth with psychiatric disorders, but little is known about use rates of antipsychotics or other psychotropic medications in patients at high risk for psychosis. Method: Baseline psychotropic medication use rates were compared in two research cohorts of patients at high risk for psychosis that enrolled between 1998-2005 (n. = 391) and 2008-2011 (n. = 346). Treatment durations and antipsychotic doses were described for cohort 2. Results: Median age was 17. years in cohort 1 and 18. years in cohort 2. The rate of prescription of any psychotropic at baseline was roughly 40% for each cohort. Antipsychotic prescription rates were 24% among sites that permitted baseline antipsychotic use in cohort 1 and 18% in the cohort 2; the decline did not quite reach statistical significance (p. = 0.064). In cohort 2 the mean. ±. SD baseline chlorpromazine-equivalent dose was 121. ±. 108. mg/d, and lifetime duration of antipsychotic treatment was 3.8. ±. 5.9. months. Discussion: Although the rate of antipsychotic prescription among high-risk youth may have fallen slightly, the nearly one-in-five rate in the second cohort still constitutes a significant exposure. Mitigating factors were that doses and durations of treatment were low. As for other nonpsychotic conditions, it is incumbent on our field to develop alternative treatments for high-risk patients and to generate additional evidence for or against the efficacy of antipsychotics to help define their appropriate role if alternative treatments fail

Latent class cluster analysis of symptom ratings identifies distinct subgroups within the clinical high risk for psychosis syndrome

The clinical-high-risk for psychosis (CHR-P) syndrome is heterogeneous in terms of clinical presentation and outcomes. Identifying more homogenous subtypes of the syndrome may help clarify its etiology and improve the prediction of psychotic illness. This study applied latent class cluster analysis (LCCA) to symptom ratings from the North American Prodrome Longitudinal Studies 1 and 2 (NAPLS 1 and 2). These analyses produced evidence for three to five subgroups within the CHR-P syndrome. Differences in negative and disorganized symptoms distinguished among the subgroups. Subgroup membership was found to predict conversion to psychosis. The authors contrast the methods employed within this study with previous attempts to identify more homogenous subgroups of CHR-P individuals and discuss how these results could be tested in future samples of CHR-P individuals

Duration of the psychosis prodrome

The recognition of a prodromal period preceding the onset of frank psychosis dates back to its first descriptions. Despite insights gained from a prospective approach to the study of the Clinical High Risk syndrome for psychosis (CHR-P), a prospectively-based understanding of the duration of the psychosis prodrome and the factors that may influence is not well-established. Here we analyze data from the second North American Prodrome Longitudinal Study (NAPLS-2) to characterize prodrome duration in those who converted to psychosis. Of the 764 participants identified as being at CHR-P, 94 converted to psychosis and 92 of these had recorded estimates of prodrome onset. Estimates of prodrome duration were derived from CHR-P syndrome onset and conversion dates from the Structured Interview for Psychosis-risk Syndromes. Results identified a mean prodrome duration of 21.6 months. Neither CHR-P sub-syndrome nor medication exposure was found to significantly influence prodrome duration in this sample. These results provide the most precise estimate of prodrome duration to date, although results are limited to prodromes identified by ascertainment as being at CHR-P. Our findings also suggest a rule of thirds with regard to prodrome duration in those followed for two years: one third of CHR-P patients who convert will do so by 1 year after CHR-P syndrome onset, another third 1–2 years after onset, and the final third more than 2 years after onset

Sleep problems and attenuated psychotic symptoms in youth at clinical high-risk for psychosis

There has been growing interest on the effect of sleep problems on psychotic and prodromal symptoms. The current study investigated cross-sectional relations between sleep problems and attenuated psychotic symptoms in a large sample of 740 youth at Clinical High Risk (CHR) for psychosis in an attempt to replicate previous findings and assess whether findings from general population samples and psychotic samples extend to this CHR sample. Sleep problems were found to be significantly positively associated with attenuated psychotic symptom severity. Sleep problems were also found to be more closely associated with certain specific prodromal symptoms (e.g., suspiciousness and perceptual abnormalities) than other attenuated psychotic symptoms. Further, we found that depression mediated the cross-sectional association between sleep problems and paranoid symptoms only. This adds to a growing body of evidence suggesting the mediation role of depression is more pronounced for paranoid-type psychotic symptoms as compared to other psychotic symptoms (e.g., hallucinations)

Incorporating cortisol into the NAPLS2 individualized risk calculator for prediction of psychosis

Background: Risk calculators are useful tools that can help clinicians and researchers better understand an individual's risk of conversion to psychosis. The North American Prodrome Longitudinal Study (NAPLS2) Individualized Risk Calculator has good predictive accuracy but could be potentially improved by the inclusion of a biomarker. Baseline cortisol, a measure of hypothalamic-pituitary-adrenal (HPA) axis functioning that is impacted by biological vulnerability to stress and exposure to environmental stressors, has been shown to be higher among individuals at clinical high-risk for psychosis (CHR–P) who eventually convert to psychosis than those who do not. We sought to determine whether the addition of baseline cortisol to the NAPLS2 risk calculator improved the performance of the risk calculator. Methods: Participants were drawn from the NAPLS2 study. A subset of NAPLS2 participants provided salivary cortisol samples. A multivariate Cox proportional hazards regression evaluated the likelihood of an individual's eventual conversion to psychosis based on demographic and clinical variables in addition to baseline cortisol levels. Results: A total of 417 NAPLS2 participants provided salivary cortisol and were included in the analysis. Higher levels of cortisol were predictive of conversion to psychosis in a univariate model (C-index = 0.59, HR = 21.5, p-value = 0.004). The inclusion of cortisol in the risk calculator model resulted in a statistically significant improvement in performance from the original risk calculator model (C-index = 0.78, SE = 0.028). Conclusions: Salivary cortisol is an inexpensive and non-invasive biomarker that could improve individual predictions about conversion to psychosis and treatment decisions for CHR-P individuals

Early traumatic experiences, perceived discrimination and conversion to psychosis in those at clinical high risk for psychosis

Purpose: There is evidence to suggest that both early traumatic experiences and perceived discrimination are associated with later onset of psychosis. Less is known about the impact these two factors may have on conversion to psychosis in those who are at clinical high risk (CHR) of developing psychosis. The purpose of this study was to determine if trauma and perceived discrimination were predictors of conversion to psychosis. Methods: The sample consisted of 764 individuals who were at CHR of developing psychosis and 280 healthy controls. All participants were assessed on past trauma, bullying and perceived discrimination. Results: Individuals at CHR reported significantly more trauma, bullying and perceived discrimination than healthy controls. Only perceived discrimination was a predictor of later conversion to psychosis. Conclusions: Given that CHR individuals are reporting increased rates of trauma and perceived discrimination, these should be routinely assessed, with the possibility of offering interventions aimed at ameliorating the impact of past traumas as well as improving self-esteem and coping strategies in an attempt to reduce perceived discrimination

Perceptual abnormalities in clinical high risk youth and the role of trauma, cannabis use and anxiety

Recent research suggests that perceptual abnormalities are a group of diverse experiences, which have been associated with trauma, cannabis use, and anxiety. Of the attenuated psychotic symptoms that are present in youth at clinical high risk (CHR) of psychosis, perceptual abnormalities tend to be one of the most frequently endorsed symptoms. However, very few studies have explored perceptual abnormalities and their relationships with the above environmental and affective factors in a CHR sample. Four hundred and forty–one CHR individuals who met criteria for attenuated psychotic symptom syndrome (APSS) determined by the Structured Interview for Psychosis-risk Syndromes (SIPS) were assessed on the content of their perceptual abnormalities, early traumatic experience, cannabis use and self-reported anxiety. Logistic regression analyses suggested that both simple auditory and simple visual perceptual abnormalities were more likely to be reported by CHR who had early traumatic experiences, who are current cannabis users, and who have higher levels of anxiety. Multiple regression analysis revealed that only trauma and anxiety were independent predictors of both simple auditory and simple visual perceptual abnormalities. It is possible that examining subtypes of perceptual abnormalities in CHR leads to an improved understanding of the prevalence of such symptoms

Treatment Precedes Positive Symptoms in North American Adolescent and Young Adult Clinical High Risk Cohort

Early intervention for psychotic disorders, a growing international priority, typically targets help-seeking populations with emerging psychotic (“positive”) symptoms. We assessed the nature of and degree to which treatment of individuals at high risk for psychosis preceded or followed the onset of positive symptoms. The North American Prodrome Longitudinal Study–2 collected psychosocial treatment histories for 745 (98%) of 764 high-risk participants (M age = 18.9, 57% male, 57.5% Caucasian, 19.1% Hispanic) recruited from 8 North American communities. Similar to prior findings, 82% of participants reported psychosocial treatment prior to baseline assessment, albeit with significant variability across sites (71%–96%). Participants first received treatment a median of 1.7 years prior to the onset of a recognizable psychosis-risk syndrome. Only one fourth sought initial treatment in the year following syndrome onset. Although mean sample age differed significantly by site, age at initial treatment (M = 14.1, SD = 5.0) did not. High rates of early treatment prior to syndrome onset make sense in light of known developmental precursors to psychotic disorders but are inconsistent with the low rates of treatment retrospectively reported by first-episode psychosis samples. Findings suggest that psychosis risk studies and clinics may need to more actively recruit and engage symptomatic but non-help-seeking individuals and that community clinicians be better trained to recognize both positive and nonspecific indicators of emerging psychosis. Improved treatments for nonspecific symptoms, as well as the characteristic attenuated positive symptoms, are needed