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Record W2904915074 · doi:10.1073/pnas.1811695115

Transgenerational hypocortisolism and behavioral disruption are induced by the antidepressant fluoxetine in male zebrafish <i>Danio rerio</i>

2018· article· en· W2904915074 on OpenAlexafffund
Marilyn N. Vera-Chang, Antony D. St‐Jacques, Rémi Gagné, Christopher J. Martyniuk, Carole L. Yauk, Thomas W. Moon, Vance L. Trudeau

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2018
Typearticle
Languageen
FieldPsychology
TopicNeuroendocrine regulation and behavior
Canadian institutionsOntario GenomicsHealth CanadaUniversity of Ottawa
FundersFonds de recherche du Québec – Nature et technologiesTrent UniversityNatural Sciences and Engineering Research Council of CanadaGovernment of CanadaHealth CanadaUniversity of Ottawa
KeywordsFluoxetineEndocrinologyDanioZebrafishInternal medicineFetusAdrenocorticotropic hormoneAntidepressantSerotoninTranscriptomeBiologyHormonePhysiologyPregnancyMedicineGeneGeneticsReceptor

Abstract

fetched live from OpenAlex

The global prevalence of depression is high during childbearing. Due to the associated risks to the mother and baby, the selective serotonin reuptake inhibitor fluoxetine (FLX) is often the first line of treatment. Given that FLX readily crosses the placenta, a fetus may be susceptible to the disruptive effects of FLX during this highly plastic stage of development. Here, we demonstrate that a 6-day FLX exposure to a fetus-relevant concentration at a critical developmental stage suppresses cortisol levels in the adult zebrafish (F 0 ). This effect persists for three consecutive generations in the unexposed descendants (F 1 to F 3 ) without diminution and is more pronounced in males. We also show that the in vivo cortisol response of the interrenal (fish “adrenal”) to an i.p. injection of adrenocorticotropic hormone was also reduced in the males from the F 0 and F 3 FLX lineages. Transcriptomic profiling of the whole kidney containing the interrenal cells revealed that early FLX exposure significantly modified numerous pathways closely associated with cortisol synthesis in the male adults from the F 0 and F 3 generations. We also show that the low cortisol levels are linked to significantly reduced exploratory behaviors in adult males from the F 0 to F 2 FLX lineages. This may be a cause for concern given the high prescription rates of FLX to pregnant women and the potential long-term negative impacts on humans exposed to these therapeutic drugs.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.009
Threshold uncertainty score0.019

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.075
GPT teacher head0.369
Teacher spread0.295 · 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 source (direct Gemma or distilled Codex), 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

Citations110
Published2018
Admission routes2
Has abstractyes

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