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Early-Stage Negative Symptom Trajectories and Relationships With 13-Year Outcomes in First-Episode Nonaffective Psychosis.

ABSTRACT: Negative symptoms are a key treatment target in early psychosis intervention. There is a paucity of research examining longitudinal course of negative symptoms across the initial years of treatment for first-episode psychosis using individual-based trajectory analysis. No study has been conducted investigating differential relationships of early-stage negative symptom trajectories with long-term distal outcomes. This study examined patterns and baseline predictors of negative symptom trajectories over the first 3 years of treatment in 138 patients aged 18-55 years presenting with first-episode nonaffective psychosis, using latent class growth analysis based on symptom ratings measured at 4 different time points (baseline, 1, 2, and 3 years). We further explored prospective relationships of identified trajectory classes with functional and negative symptom outcomes at 13-year follow-up. Our results revealed 3 distinct negative symptom trajectories including minimal-stable (59.6%), mild-stable (29.4%), and high-increasing (11.0%) trajectories. Poorer premorbid adjustment, more severe global cognitive impairment, and depressive symptoms at baseline were found to predict high-increasing trajectory. Among 3 trajectory classes, patients in high-increasing trajectory had the worst functional and negative symptom outcomes at 13-year follow-up, with post hoc analyses demonstrating significant outcome differences between high-increasing and minimal-stable trajectories. Our findings thus affirm a heterogeneous course of negative symptoms in first-episode psychosis and indicate that early-stage negative symptom trajectories are critically associated with long-term outcomes. Patients displaying persistently high negative symptom levels in the initial 3 years of treatment may represent a specific subgroup who necessitates an extended period of early intervention specifically targeting at negative symptoms to promote early functional recovery.

SUBMITTER: Chang WC

PROVIDER: S-EPMC6483573 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Early-Stage Negative Symptom Trajectories and Relationships With 13-Year Outcomes in First-Episode Nonaffective Psychosis.

Chang Wing Chung WC Ho Ryan Wui Hang RWH Tang Jennifer Yee Man JYM Wong Corine Sau Man CSM Hui Christy Lai Ming CLM Chan Sherry K W SKW Lee Edwin M H EMH Suen Yi Nam YN Chen Eric Y H EYH

Schizophrenia bulletin 20190401 3

Negative symptoms are a key treatment target in early psychosis intervention. There is a paucity of research examining longitudinal course of negative symptoms across the initial years of treatment for first-episode psychosis using individual-based trajectory analysis. No study has been conducted investigating differential relationships of early-stage negative symptom trajectories with long-term distal outcomes. This study examined patterns and baseline predictors of negative symptom trajectorie ...[more]

PMID: 30124959

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Project description:ImportanceIn coordinated specialty care (CSC) settings for people with a first episode of psychosis, the development of reliable, validated individual-level prediction tools for key outcomes may be informative for shared clinician and client decision-making.ObjectiveTo develop an individual-level prediction tool using machine-learning methods that predicts a trajectory of education/work status or psychiatric hospitalization outcomes over a client's next year of quarterly follow-up assessments. Additionally, to visualize these predictions in a way that is informative to clinicians and clients.Design, setting, and participantsIndividual-level data were collected for all patients enrolled in the OnTrackNY program at enrollment and at quarterly follow-ups using standardized forms. The OnTrackNY program, a network of CSC sites in New York State, provides person-centered, recovery-oriented, and evidence-based psychosocial and pharmaceutical interventions to individuals aged 16 to 30 years with recent-onset (<2 years) nonaffective psychosis. Although data collection is ongoing, data for this study were collected from October 2013 to December 2018, and the time frame for analysis was July 2020 to May 2021. Data were separated into a training/cross-validation set to perform internally validated model development and a separate holdout test set (~20% of the sample) for external validation. Random probability forest models were developed to predict individual-level trajectories of outcomes.ExposuresForty-three individual-level demographic and clinical features collected at enrollment in OnTrackNY, 25 of which were time-varying and updated at quarterly follow-up assessments, and 13 site-level demographic and economic census variables.Main outcomes and measuresIndividual-level education and/or employment status and psychiatric hospitalization trajectories at quarterly follow-up periods across the first 2 years of CSC.ResultsThe total study sample consists of 1298 individuals aged 16 to 30 years and included 341 women (26.3%), 949 men (73.1%), and 8 (<1%) with another gender. Prediction models performed well for 1-year trajectories of education/work across all validation sets, with areas under the receiver operating characteristic curve (AUCs) ranging from 0.68 (95% CI, 0.63-0.74) to 0.88 (95% CI, 0.81-0.96). Predictive accuracy for psychiatric hospitalization 3 months ahead reached AUC above 0.70; moreover, predictions of future psychiatric hospitalizations at 6 months and beyond were consistently poor, with AUCs below 0.60. Given the good externally validated performance for predicting education/work, a prototype interactive visualization tool displaying individual-level education/work trajectories and related features was developed.Conclusions and relevanceThis study suggests that accurate prediction tools can be developed for outcomes in people with first-episode psychosis, which may help inform shared clinician/client decision-making. Future work should study the effectiveness of its deployment, including proper communication to inform shared clinician/client decision-making in the context of a learning health care system. At present, more work is needed to develop better performing prediction models for future psychiatric hospitalizations before any tool is recommended for this outcome.

Project description:BackgroundThe neurodevelopmental model of psychosis was established over 30 years ago; however, the developmental influence on psychotic symptom expression - how age affects clinical presentation in first-episode psychosis - has not been thoroughly investigated.MethodsUsing generalized additive modeling, which allows for linear and non-linear functional forms of age-related change, we leveraged symptom data from a large sample of antipsychotic-naïve individuals with first-episode psychosis (N = 340, 12-40 years, 1-12 visits), collected at the University of Pittsburgh from 1990 to 2017. We examined relationships between age and severity of perceptual and non-perceptual positive symptoms and negative symptoms. We tested for age-associated effects on change in positive or negative symptom severity following baseline assessment and explored the time-varying relationship between perceptual and non-perceptual positive symptoms across adolescent development.ResultsPerceptual positive symptom severity significantly decreased with increasing age (F = 7.0, p = 0.0007; q = 0.003) while non-perceptual positive symptom severity increased with age (F = 4.1, p = 0.01, q = 0.02). Anhedonia severity increased with increasing age (F = 6.7, p = 0.00035; q = 0.0003), while flat affect decreased in severity with increased age (F = 9.8, p = 0.002; q = 0.006). Findings remained significant when parental SES, IQ, and illness duration were included as covariates. There were no developmental effects on change in positive or negative symptom severity (all p > 0.25). Beginning at age 18, there was a statistically significant association between severity of non-perceptual and perceptual symptoms. This relationship increased in strength throughout adulthood.ConclusionsThese findings suggest that as maturation proceeds, perceptual symptoms attenuate while non-perceptual symptoms are enhanced. Findings underscore how pathological brain-behavior relationships vary as a function of development.

Project description:BACKGROUND:Early illness course correlates with long-term outcome in psychosis. Accurate prediction could allow more focused intervention. Earlier intervention corresponds to significantly better symptomatic and functional outcomes. Our study objective is to use routinely collected baseline demographic and clinical characteristics to predict employment, education or training (EET) status, and symptom remission in patients with first episode psychosis (FEP) at one-year. METHODS AND FINDINGS:83 FEP patients were recruited from National Health Service (NHS) Glasgow between 2011 and 2014 to a 24-month prospective cohort study with regular assessment of demographic and psychometric measures. An external independent cohort of 79 FEP patients were recruited from NHS Glasgow and Edinburgh during a 12-month study between 2006 and 2009. Elastic net regularised logistic regression models were built to predict binary EET status, period and point remission outcomes at one-year on 83 Glasgow patients (training dataset). Models were externally validated on an independent dataset of 79 patients from Glasgow and Edinburgh (validation dataset). Only baseline predictors shared across both cohorts were made available for model training and validation. After excluding participants with missing outcomes, models were built on the training dataset for EET status, period and point remission outcomes and externally validated on the validation dataset. Models predicted EET status, period and point remission with receiver operating curve (ROC) area under the curve (AUC) performances of 0.876 (95%CI: 0.864, 0.887), 0.630 (95%CI: 0.612, 0.647) and 0.652 (95%CI: 0.635, 0.670) respectively. Positive predictors of EET included baseline EET and living with spouse/children. Negative predictors included higher PANSS suspiciousness, hostility and delusions scores. Positive predictors for symptom remission included living with spouse/children, and affective symptoms on the Positive and Negative Syndrome Scale (PANSS). Negative predictors of remission included passive social withdrawal symptoms on PANSS. A key limitation of this study is the small sample size (n) relative to the number of predictors (p), whereby p approaches n. The use of elastic net regularised regression rather than ordinary least squares regression helped circumvent this difficulty. Further, we did not have information for biological and additional social variables, such as nicotine dependence, which observational studies have linked to outcomes in psychosis. CONCLUSIONS AND RELEVANCE:Using advanced statistical machine learning techniques, we provide the first externally validated evidence, in a temporally and geographically independent cohort, for the ability to predict one-year EET status and symptom remission in individual FEP patients.

Dataset Information

Early-Stage Negative Symptom Trajectories and Relationships With 13-Year Outcomes in First-Episode Nonaffective Psychosis.

Publications

Early-Stage Negative Symptom Trajectories and Relationships With 13-Year Outcomes in First-Episode Nonaffective Psychosis.

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