Dataset Information

Brain function, structure and genomic data are linked but show different sensitivity to duration of illness and disease stage in schizophrenia.

ABSTRACT: The progress of schizophrenia at various stages is an intriguing question, which has been explored to some degree using single-modality brain imaging data, e.g. gray matter (GM) or functional connectivity (FC). However it remains unclear how those changes from different modalities are correlated with each other and if the sensitivity to duration of illness and disease stages across modalities is different. In this work, we jointly analyzed FC, GM volume and single nucleotide polymorphisms (SNPs) data of 159 individuals including healthy controls (HC), drug-naïve first-episode schizophrenia (FESZ) and chronic schizophrenia patients (CSZ), aiming to evaluate the links among SNP, FC and GM patterns, and their sensitivity to duration of illness and disease stages in schizophrenia. Our results suggested: 1) both GM and FC highlighted impairments in hippocampal, temporal gyrus and cerebellum in schizophrenia, which were significantly correlated with genes like SATB2, GABBR2, PDE4B, CACNA1C etc. 2) GM and FC presented gradually decrease trend (HC?>?FESZ>CSZ), while SNP indicated a non-gradual variation trend with un-significant group difference observed between FESZ and CSZ; 3) Group difference between HC and FESZ of FC was more remarkable than GM, and FC presented a stronger negative correlation with duration of illness than GM (p?=?0.0006). Collectively, these results highlight the benefit of leveraging multimodal data and provide additional clues regarding the impact of mental illness at various disease stages.

SUBMITTER: Luo N

PROVIDER: S-EPMC6558215 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Brain function, structure and genomic data are linked but show different sensitivity to duration of illness and disease stage in schizophrenia.

Luo Na N Tian Lin L Calhoun Vince D VD Chen Jiayu J Lin Dongdong D Vergara Victor M VM Rao Shuquan S Yang Jian J Zhuo Chuanjun C Xu Yong Y Turner Jessica A JA Zhang Fuquan F Sui Jing J

NeuroImage. Clinical 20190531

The progress of schizophrenia at various stages is an intriguing question, which has been explored to some degree using single-modality brain imaging data, e.g. gray matter (GM) or functional connectivity (FC). However it remains unclear how those changes from different modalities are correlated with each other and if the sensitivity to duration of illness and disease stages across modalities is different. In this work, we jointly analyzed FC, GM volume and single nucleotide polymorphisms (SNPs) ...[more]

PMID: 31176952

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Project description:Abstract Background: Cariprazine (CAR) is a D3/D2 receptor partial agonist antipsychotic approved for treatment of adults with acute exacerbation of schizophrenia. Many patients with schizophrenia display a progressive worsening of symptomatology, a process that has the potential to impede treatment response. These post hoc analyses were performed to evaluate CAR efficacy in subsets of patients at different stages of disease progression. Methods: Data were pooled from 3 randomized, 6-week, double-blind, placebo (PBO)-controlled Phase II/III trials of CAR efficacy and safety in patients with schizophrenia (NCT01104766, NCT01104779, NCT00694707). For this post hoc analysis, data were grouped according to number of previous episodes (<5, 5–10, >10), duration of schizophrenia in years (?5.1, 5.2–13.4, >13.4), or number of previous psychiatric hospitalizations (?2, 3–6, >6). Efficacy outcomes were change from baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) total score, PANSS Positive and Negative subscales, and Clinical Global Impression of Severity scale (CGI-S); data were analyzed using a mixed-effects model for repeated measures. Results: At all stages of illness, patients treated with CAR (n = 1024) showed a significantly greater improvement on PANSS and CGI-S total scores than did those treated with PBO (n = 442). Compared with PBO, CAR significantly reduced mean PANSS total score in patients regardless of number of previous episodes (<5: least squares mean difference [LSMD] ?8.0, P < .0001; 5–10: LSMD ?6.3, P = .0018; >10: LSMD ?9.2, P = .0001), duration of schizophrenia (?5.1 years: LSMD ?7.6, P = .0002; 5.2–13.4 years: LSMD ?8.5, P < .0001; >13.4 years: LSMD ?7.6, P = .0003), or number of previous psychiatric hospitalizations (0–2: LSMD ?5.6, P = .0030; 3–6: LSMD ?9.7, P < .0001; >6: LSMD ?9.6, P < .0001). CAR also significantly reduced mean CGI-S overall score relative to PBO in patients regardless of number of previous episodes (<5: LSMD ?0.4, P = .0005; 5–10: LSMD ?0.2, P = .0385; >10: LSMD ?0.7, P < .0001), duration of schizophrenia (?5.1 years: LSMD ?0.3, P = .0041; 5.2–13.4 years: LSMD ?0.5, P < .0001; >13.4 years: LSMD ?0.3, P = .0017), or number of previous psychiatric hospitalizations (0–2: LSMD ?0.3, P = .0133; 3–6: LSMD ?0.4, P < .0001; >6: LSMD ?0.6, P < .0001). Similar results were observed on the PANSS Positive and Negative subscales. Conclusion: Cariprazine was efficacious in the overall adult population. When stratified by number of previous episodes experienced, duration of schizophrenia, or number of previous psychiatric hospitalizations, no consistent trends in magnitude of efficacy were evident; however, cariprazine efficacy in patients at the later stages of illness was similar to or greater than that in patients at earlier stages, suggesting that cariprazine is effective in the treatment of schizophrenia in adults regardless of the stage of illness progression.

Dataset Information

Brain function, structure and genomic data are linked but show different sensitivity to duration of illness and disease stage in schizophrenia.

Publications

Brain function, structure and genomic data are linked but show different sensitivity to duration of illness and disease stage in schizophrenia.

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