Antidepressants　are　among　the　most　commonly　detected　pharmaceuticals　in　aqueous　systems,　and,　as　emerging　organic　pollutants,　may　exert　negative　effects　on　non-target　aquatic　organisms.　Previously,　it　has　been　revealed　that　antidepressant　exposure　significantly　inhibits　the　growth　and　development　of　fish　during　their　early　developmental　stages.　Thus,　in　the　present　study,　we　aimed　to　identify　and　compare　the　underlying　mechanisms　of　action　of　different　antidepressants　at　the　transcriptional　level　using　zebrafish　(Dario　rerio)　embryos.　Through　high-throughput　RNA　sequencing　(RNA-Seq)　data　analysis,　32,　34,　and　130　differentially　expressed　genes　(DEGs)　were　obtained　from　zebrafish　larvae　after　120　h　of　embryonic　exposure　to　sublethal　concentrations　of　amitriptyline,　fluoxetine,　and　mianserin,　respectively.　The　expression　profiles　of　the　identified　DEGs　showed　similar　trends　in　response　to　the　three　antidepressant　treatments,　suggesting　consistent　toxic　effects　of　low　concentrations　of　these　three　drugs　on　the　regulation　of　gene　expression　in　fish.　Several　metabolic　and　signaling　pathways,　including　glycolysis/gluconeogenesis　and　the　insulin　pathway,　were　affected　in　the　exposed　fish　larvae.　The　expression　profiles　of　selected　DEGs　were　then　verified　by　the　qRT-PCR　method,　which　indicated　significant　positive　correlations　with　the　RNA-Seq　results.　Next,　we　determined　the　concentration-dependent　expression　patterns　of　6　selected　DEGs　in　fish　larvae　exposed　to　three　antidepressants　at　a　series　of　environmentally　relevant　concentrations.　The　results　revealed　a　significant　concentration-dependent　reduction　in　the　levels　of　dual-specificity　phosphatase　5　(dusp5)　mRNA,　as　well　as　a　non-concentration-dependent　gene　expression　inhibition　of　prostaglandin　D2　synthase　b　(ptgdsb);　the　circadian　rhythm-related　genes,　i.e.　those　encoding　nuclear　receptor　subfamily　1,　group　D,　member　1　(nr1d1)　and　period　2　(pert);　and　genes　encoding　early　growth　response　factors　(egr1　and　egr4),　in　the　antidepressant-treated　fish　larvae.　In　summary,　to　our　knowledge,　our　findings　demonstrate,　for　the　first　time,　that　the　three　different　categories　of　antidepressants　have　common　effects　on　the　gene　expression　involved　in　multiple　biological　processes　and　signaling　pathways　during　the　early　development　of　fish　and　thus　provide　information　for　characterizing　the　adverse　outcome　pathways　and　on　the　ecological　risk　assessment　of　these　pharmaceutical　pollutants　in　the　aquatic　environment.