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Blood Gene Expression Profile Predicts Response to Antipsychotics.

ABSTRACT: Antipsychotic drugs are one of the largest types of prescribed drugs and have large inter-individual differences in efficacy, but there is no methodology to predict their clinical effect. Here we show a four-gene blood expression profile to predict the response to antipsychotics in schizophrenia patients before treatment. We sequenced total mRNA from blood samples of antipsychotic naïve patients who, after 3 months of treatment, were in the top 40% with the best response (15 patients) and in the bottom 40% with the worst response (15 patients) according to the Brief Psychiatric Rating Scale (BPRS). We characterized the transcriptome before treatment of these 30 patients and found 130 genes with significant differential expression (Padj value < 0.01) associated with clinical response. Then, we used Random Forests, an ensemble learning method for classification and regression, to obtain a list of predictor genes. The expression of four genes can predict the response to antipsychotic medication with a cross-validation accuracy estimation of 0.83 and an area under the curve of 0.97 using a logistic regression. We anticipate that this approach is a gateway to select the specific antipsychotic that will produce the best response to treatment for each specific patient.

SUBMITTER: Sainz J

PROVIDER: S-EPMC5845714 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Blood Gene Expression Profile Predicts Response to Antipsychotics.

Sainz Jesus J Prieto Carlos C Ruso-Julve Fulgencio F Crespo-Facorro Benedicto B

Frontiers in molecular neuroscience 20180306

Antipsychotic drugs are one of the largest types of prescribed drugs and have large inter-individual differences in efficacy, but there is no methodology to predict their clinical effect. Here we show a four-gene blood expression profile to predict the response to antipsychotics in schizophrenia patients before treatment. We sequenced total mRNA from blood samples of antipsychotic naïve patients who, after 3 months of treatment, were in the top 40% with the best response (15 patients) and in the ...[more]

PMID: 29559890

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Project description:ImportanceInduced hypothermia, the standard treatment for hypoxic-ischemic encephalopathy (HIE) in high-income countries (HICs), is less effective in the low-income populations in South Asia, who have the highest disease burden.ObjectiveTo investigate the differences in blood genome expression profiles of neonates with HIE from an HIC vs neonates with HIE from South Asia.Design, setting, and participantsThis case-control study analyzed data from (1) a prospective observational study involving neonates with moderate or severe HIE who underwent whole-body hypothermia between January 2017 and June 2019 and age-matched term healthy controls in Italy and (2) a randomized clinical trial involving neonates with moderate or severe HIE in India, Sri Lanka, and Bangladesh recruited between August 2015 and February 2019. Data were analyzed between October 2020 and August 2023.ExposureWhole-blood RNA that underwent next-generation sequencing.Main outcome and measuresThe primary outcomes were whole-blood genome expression profile at birth associated with adverse outcome (death or disability at 18 months) after HIE in the HIC and South Asia cohorts and changes in whole-genome expression profile during the first 72 hours after birth in neonates with HIE and healthy controls from the HIC cohort. Blood samples for RNA extraction were collected before whole-body hypothermia at 4 time points (6, 24, 48, and 72 hours after birth) for the HIC cohort. Only 1 blood sample was drawn within 6 hours after birth for the South Asia cohort.ResultsThe HIC cohort was composed of 35 neonates (21 females [60.0%]) with a median (IQR) birth weight of 3.3 (3.0-3.6) kg and gestational age of 40.0 (39.0-40.6) weeks. The South Asia cohort consisted of 99 neonates (57 males [57.6%]) with a median (IQR) birth weight of 2.9 (2.7-3.3) kg and gestational age of 39.0 (38.0-40.0) weeks. Healthy controls included 14 neonates (9 females [64.3%]) with a median (IQR) birth weight of 3.4 (3.2-3.7) kg and gestational age of 39.2 (38.9-40.4) weeks. A total of 1793 significant genes in the HIC cohort and 99 significant genes in the South Asia cohort were associated with adverse outcome (false discovery rate <0.05). Only 11 of these genes were in common, and all had opposite direction in fold change. The most significant pathways associated with adverse outcome were downregulation of eukaryotic translation initiation factor 2 signaling in the HIC cohort (z score = -4.56; P < .001) and aldosterone signaling in epithelial cells in the South Asia cohort (z score = null; P < .001). The genome expression profile of neonates with HIE (n = 35) at birth, 24 hours, 48 hours, and 72 hours remained significantly different from that of age-matched healthy controls in the HIC cohort (n = 14).Conclusions and relevanceThis case-control study found that disease mechanisms underlying HIE were primarily associated with acute hypoxia in the HIC cohort and nonacute hypoxia in the South Asia cohort. This finding might explain the lack of hypothermic neuroprotection.

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Blood Gene Expression Profile Predicts Response to Antipsychotics.

Publications

Blood Gene Expression Profile Predicts Response to Antipsychotics.

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