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Record W2794858017 · doi:10.1093/schbul/sby016.468

T192. THE GUT MICROBIOME IN SCHIZOPHRENIA AND ANTIPSYCHOTIC INDUCED METABOLIC DYSFUNCTION

2018· article· en· W2794858017 on OpenAlexaff
Sarah Kanji, Ilona Gorbovskaya, Trehani M. Fonseka, Kazunari Yoshida, Victoria Marshe, Malgorzata MacKenzie, Přemysl Berčík, Elena F. Verdú, Margaret Hahn, Daniel J. Müller

Bibliographic record

VenueSchizophrenia Bulletin · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGut microbiota and health
Canadian institutionsUniversity of TorontoMcMaster UniversityCentre for Addiction and Mental Health
Fundersnot available
KeywordsSchizophrenia (object-oriented programming)MedicineAntipsychoticInternal medicineMicrobiomeMetabolic syndromeClozapineBody mass indexObesityPsychiatryBioinformaticsBiology

Abstract

fetched live from OpenAlex

Antipsychotic (AP) medications are the cornerstone of treatment for schizophrenia (SCZ), with off-label prescription rapidly increasing in youth and adolescent populations. However, APs have been associated with metabolic side effects including diabetes and obesity. Although several mechanisms have been proposed, the gut microbiome (GMB) has been suggested as a potential mediator of AP-induced metabolic side effects due to its role in weight and metabolic regulation; as well as emerging evidence demonstrating a shift in the microbiome of AP-treated animals and humans. The purpose of the current study is to 1) Investigate the GMB in SCZ patients compared to healthy individuals and 2) To examine the role of GMB in SCZ and AP-induced metabolic side effects. Three groups of 25 participants are being recruited. Group A: Long-term AP-treated patients (for at least 6 months) taking clozapine (CLZ). Group B: Healthy controls matched with Group A for BMI, age, sex, and smoking status. Group C: Treatment-naive SCZ patients starting an AP or patients newly switching to CLZ. Groups A and B will be assessed at a single time point (week 0) whereas Group C will be assessed prospectively at weeks 0, 3, and 12 with the same measures collected. The following clinical measures and metabolic indices are collected at baseline, and if applicable, at follow up visits: the Questionnaire of Eating and Weight Patterns (QEWP), the Dutch Eating Behavior Questionnaire (DEBQ), the Power of Food Scale (POFS), the Positive and Negative Syndrome Scale (PANSS), the Gastrointestinal Symptom Rating Scale (GSRS), Exercise/Physical Activity Evaluation, body mass index, oral glucose tolerance test, lipid profile, and serum clozapine levels. We also collect fecal samples for DNA extraction and microbiome sequencing. We are currently performing a baseline comparison across groups A, B, and C in order to evaluate intrinsic differences between schizophrenia and healthy controls, as well as, effects of new AP exposure versus chronic exposure. The difference between analytical groups (i.e. groups A, B, and C) at different time points (i.e. baseline, week 3 and 6) for variables such as BMI and metabolic parameters marker change are analyzed using two-way repeated measures ANCOVA, including significant covariates. The relationship between different measures, such as body weight and metabolic parameters, GMB composition (abundance of each species), and AIWG will be tested using Spearman’s correlation. Analysis of the Operational Taxonomic Unit network generated using QIIME will be further analyzed using linear discriminant analysis (LDA) effect size (LEfSe) method. This method uses LDA scores to estimate the effect size of differentially abundant taxa (at phyla, class or other levels) and ranks the relative difference of microbial taxa that discriminate groups with biological consistency and statistical significance. The GMB composition of within group weight gainers versus non-weight gainer will also be assessed in a subgroup of subjects using LEfSe. To date, 17 patients enrolled (13 patients in group A (9 men, mean±SD age: 31.6 ± 5.1 years; BMI, 31.4 ± 5.5), two control in group B (1 men, mean±SD age: 29.0 ± 1.4 years; BMI, 30.3 ± 0.8), two in group C (1 men, mean±SD age: 30.0 ± 9.9 years; BMI, 25.8 ± 5.6)). Further analyses including GMB composition in each group are now being conducted. We are currently analyzing these individuals for their GMB composition and results will be presented at the SIRS meeting. To our knowledge, this is the first study to assess GMB sample in SCZ and investigate the association the GMB and AP-induced metabolic side effects. Our study has the potential to help to unravel the role of GMB in SCZ and AP response.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.903
Threshold uncertainty score0.809

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.244
Teacher spread0.234 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2018
Admission routes1
Has abstractyes

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