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The longitudinal interplay between negative and positive symptom trajectories in patients under antipsychotic treatment: a post hoc analysis of data from a randomized, 1-year pragmatic trial.

Chen L, Johnston JA, Kinon BJ, Stauffer V, Succop P, Marques TR, Ascher-Svanum H - BMC Psychiatry (2013)

Bottom Line: Correlation coefficients for changes in negative and positive symptom subscale scores were positive and statistically significant (P < 0.05).Overall, the combined trajectories indicated three major distinct patterns: (1) dramatic and sustained early improvement in both negative and positive symptoms (n = 70, 18%), (2) mild and sustained improvement in negative and positive symptoms (n = 237, 59%), and (3) no improvement in either negative or positive symptoms (n = 82, 21%).This study of symptom trajectories over 1 year shows that changes in negative and positive symptoms were neither inversely nor independently related with each other.

View Article: PubMed Central - HTML - PubMed

Affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Chen_lei_lc@lilly.com.

ABSTRACT

Background: Schizophrenia is a highly heterogeneous disorder with positive and negative symptoms being characteristic manifestations of the disease. While these two symptom domains are usually construed as distinct and orthogonal, little is known about the longitudinal pattern of negative symptoms and their linkage with the positive symptoms. This study assessed the temporal interplay between these two symptom domains and evaluated whether the improvements in these symptoms were inversely correlated or independent with each other.

Methods: This post hoc analysis used data from a multicenter, randomized, open-label, 1-year pragmatic trial of patients with schizophrenia spectrum disorder who were treated with first- and second-generation antipsychotics in the usual clinical settings. Data from all treatment groups were pooled resulting in 399 patients with complete data on both the negative and positive subscale scores from the Positive and Negative Syndrome Scale (PANSS). Individual-based growth mixture modeling combined with interplay matrix was used to identify the latent trajectory patterns in terms of both the negative and positive symptoms. Pearson correlation coefficients were calculated to examine the relationship between the changes of these two symptom domains within each combined trajectory pattern.

Results: We identified four distinct negative symptom trajectories and three positive symptom trajectories. The trajectory matrix formed 11 combined trajectory patterns, which evidenced that negative and positive symptom trajectories moved generally in parallel. Correlation coefficients for changes in negative and positive symptom subscale scores were positive and statistically significant (P < 0.05). Overall, the combined trajectories indicated three major distinct patterns: (1) dramatic and sustained early improvement in both negative and positive symptoms (n = 70, 18%), (2) mild and sustained improvement in negative and positive symptoms (n = 237, 59%), and (3) no improvement in either negative or positive symptoms (n = 82, 21%).

Conclusions: This study of symptom trajectories over 1 year shows that changes in negative and positive symptoms were neither inversely nor independently related with each other. The positive association between these two symptom domains supports the notion that different symptom domains in schizophrenia may depend on each other through a unified upstream pathological disease process.

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Negative symptom trajectories. A: Estimated and observed mean curves. Triangles indicate estimated means, and circles indicate observed means. B: Individual profiles by negative symptom trajectories. Light gray lines show trajectory of negative symptom subscale for each patient in each latent class. Bold lines show observed mean trajectories of the corresponding latent classes.
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Figure 1: Negative symptom trajectories. A: Estimated and observed mean curves. Triangles indicate estimated means, and circles indicate observed means. B: Individual profiles by negative symptom trajectories. Light gray lines show trajectory of negative symptom subscale for each patient in each latent class. Bold lines show observed mean trajectories of the corresponding latent classes.

Mentions: To identify the different trajectory subtypes in terms of negative symptoms, data from 400 patients with complete 1-year PANSS negative subscale scores were fit to a sequential series of quadratic growth models that reflected one to five different trajectory latent classes. The statistical indices associated with the series of models (i.e., one to five latent classes) are shown in Table 2. Per the aBIC (the lower, the better) and BLRT, the four-trajectory model outperformed the other models. Figure 1A shows the observed and estimated mean PANSS negative subscale scores by the latent classes of the four-trajectory solution. There were 44, 284, 9, and 63 patients in each latent class, which represented 11%, 71%, 2%, and 16% of the entire cohort, respectively. Although the smallest group accounts for only 2% of the patients, its symptom profile is exclusive (i.e., a continuous and robust response in PANSS negative subscale score through the course of the study). Thus, we chose to keep this distinct group and, as such, the four-trajectory solution. Figure 1B shows the trajectory of the negative symptom subscale for each patient in each latent class and the observed mean trajectory of the corresponding latent class. The mean trajectory of each class demonstrated a reasonable level of concordance with individual patient trajectories and provided straightforward evidence supporting the four-trajectory solution.


The longitudinal interplay between negative and positive symptom trajectories in patients under antipsychotic treatment: a post hoc analysis of data from a randomized, 1-year pragmatic trial.

Chen L, Johnston JA, Kinon BJ, Stauffer V, Succop P, Marques TR, Ascher-Svanum H - BMC Psychiatry (2013)

Negative symptom trajectories. A: Estimated and observed mean curves. Triangles indicate estimated means, and circles indicate observed means. B: Individual profiles by negative symptom trajectories. Light gray lines show trajectory of negative symptom subscale for each patient in each latent class. Bold lines show observed mean trajectories of the corresponding latent classes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219503&req=5

Figure 1: Negative symptom trajectories. A: Estimated and observed mean curves. Triangles indicate estimated means, and circles indicate observed means. B: Individual profiles by negative symptom trajectories. Light gray lines show trajectory of negative symptom subscale for each patient in each latent class. Bold lines show observed mean trajectories of the corresponding latent classes.
Mentions: To identify the different trajectory subtypes in terms of negative symptoms, data from 400 patients with complete 1-year PANSS negative subscale scores were fit to a sequential series of quadratic growth models that reflected one to five different trajectory latent classes. The statistical indices associated with the series of models (i.e., one to five latent classes) are shown in Table 2. Per the aBIC (the lower, the better) and BLRT, the four-trajectory model outperformed the other models. Figure 1A shows the observed and estimated mean PANSS negative subscale scores by the latent classes of the four-trajectory solution. There were 44, 284, 9, and 63 patients in each latent class, which represented 11%, 71%, 2%, and 16% of the entire cohort, respectively. Although the smallest group accounts for only 2% of the patients, its symptom profile is exclusive (i.e., a continuous and robust response in PANSS negative subscale score through the course of the study). Thus, we chose to keep this distinct group and, as such, the four-trajectory solution. Figure 1B shows the trajectory of the negative symptom subscale for each patient in each latent class and the observed mean trajectory of the corresponding latent class. The mean trajectory of each class demonstrated a reasonable level of concordance with individual patient trajectories and provided straightforward evidence supporting the four-trajectory solution.

Bottom Line: Correlation coefficients for changes in negative and positive symptom subscale scores were positive and statistically significant (P < 0.05).Overall, the combined trajectories indicated three major distinct patterns: (1) dramatic and sustained early improvement in both negative and positive symptoms (n = 70, 18%), (2) mild and sustained improvement in negative and positive symptoms (n = 237, 59%), and (3) no improvement in either negative or positive symptoms (n = 82, 21%).This study of symptom trajectories over 1 year shows that changes in negative and positive symptoms were neither inversely nor independently related with each other.

View Article: PubMed Central - HTML - PubMed

Affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Chen_lei_lc@lilly.com.

ABSTRACT

Background: Schizophrenia is a highly heterogeneous disorder with positive and negative symptoms being characteristic manifestations of the disease. While these two symptom domains are usually construed as distinct and orthogonal, little is known about the longitudinal pattern of negative symptoms and their linkage with the positive symptoms. This study assessed the temporal interplay between these two symptom domains and evaluated whether the improvements in these symptoms were inversely correlated or independent with each other.

Methods: This post hoc analysis used data from a multicenter, randomized, open-label, 1-year pragmatic trial of patients with schizophrenia spectrum disorder who were treated with first- and second-generation antipsychotics in the usual clinical settings. Data from all treatment groups were pooled resulting in 399 patients with complete data on both the negative and positive subscale scores from the Positive and Negative Syndrome Scale (PANSS). Individual-based growth mixture modeling combined with interplay matrix was used to identify the latent trajectory patterns in terms of both the negative and positive symptoms. Pearson correlation coefficients were calculated to examine the relationship between the changes of these two symptom domains within each combined trajectory pattern.

Results: We identified four distinct negative symptom trajectories and three positive symptom trajectories. The trajectory matrix formed 11 combined trajectory patterns, which evidenced that negative and positive symptom trajectories moved generally in parallel. Correlation coefficients for changes in negative and positive symptom subscale scores were positive and statistically significant (P < 0.05). Overall, the combined trajectories indicated three major distinct patterns: (1) dramatic and sustained early improvement in both negative and positive symptoms (n = 70, 18%), (2) mild and sustained improvement in negative and positive symptoms (n = 237, 59%), and (3) no improvement in either negative or positive symptoms (n = 82, 21%).

Conclusions: This study of symptom trajectories over 1 year shows that changes in negative and positive symptoms were neither inversely nor independently related with each other. The positive association between these two symptom domains supports the notion that different symptom domains in schizophrenia may depend on each other through a unified upstream pathological disease process.

Show MeSH
Related in: MedlinePlus