{"doi":"10.1101/2020.02.10.927012","title":"Alterations in Acylcarnitines, Amines, and Lipids Inform about Mechanism of Action of Citalopram/Escitalopram in Major Depression","abstract":"Abstract Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and response to citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled into the Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) were profiled at baseline and after 8 weeks of treatment. After treatment, we saw increased levels of short-chain acylcarnitines and decreased levels of medium- and long-chain acylcarnitines, suggesting an SSRI effect on β-oxidation and mitochondrial function. Amines – including arginine, proline, and methionine-sulfoxide – were upregulated while serotonin and sarcosine were downregulated, suggesting an SSRI effect on urea cycle, one-carbon metabolism and serotonin uptake. Eighteen lipids within the phosphatidylcholine (PC aa and ae) classes were upregulated. Changes in several lipid and amine levels correlated with changes in 17-item Hamilton Rating Scale for Depression scores (HRSD 17 ). Differences in metabolic profiles at baseline and post-treatment were noted between participants who remitted (HRSD 17 ≤7) and those who gained no meaningful benefits (<30% reduction in HRSD 17 ). Remitters exhibited a) higher baseline levels of C3, C5, alpha-aminoadipic acid, sarcosine and serotonin; and b) higher week-8 levels of PC aa C34:1, PC aa C34:2, PC aa C36:2 and PC aa C36:4. These findings suggest that mitochondrial energetics – including acylcarnitine metabolism, transport and its link to β-oxidation – and lipid membrane remodeling may play roles in SSRI treatment response.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":120244,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9468,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":557270,"name":"Ahmed T. Ahmed","orcid":"0000-0003-4349-4509","position":1,"is_corresponding":false},{"id":245215,"name":"Sudeepa Bhattacharyya","orcid":"0000-0003-3493-6029","position":2,"is_corresponding":false},{"id":232153,"name":"Xianlin Han","orcid":"0000-0002-8615-2413","position":3,"is_corresponding":false},{"id":244573,"name":"Rebecca Baillie","orcid":"0000-0003-3966-6320","position":4,"is_corresponding":false},{"id":244565,"name":"Matthias Arnold","orcid":"0000-0002-4666-0923","position":5,"is_corresponding":false},{"id":557271,"name":"Michelle Skime","orcid":"0000-0001-7863-3017","position":6,"is_corresponding":false},{"id":110390,"name":"Lisa St. John‐Williams","orcid":null,"position":7,"is_corresponding":false},{"id":32984,"name":"M. Arthur Moseley","orcid":"0000-0001-9907-738X","position":8,"is_corresponding":false},{"id":51712,"name":"Paul M. Thompson","orcid":"0000-0002-4720-8867","position":9,"is_corresponding":false},{"id":244570,"name":"Gregory Louie","orcid":"0000-0002-3267-7070","position":10,"is_corresponding":false},{"id":353614,"name":"Patricio Riva‐Posse","orcid":"0000-0002-5887-0557","position":11,"is_corresponding":false},{"id":58338,"name":"W. Edward Craighead","orcid":"0000-0001-9957-0027","position":12,"is_corresponding":false},{"id":275887,"name":"William M. McDonald","orcid":"0000-0002-7187-5424","position":13,"is_corresponding":false},{"id":88836,"name":"Ranga Krishnan","orcid":"0000-0002-3661-8449","position":14,"is_corresponding":false},{"id":69367,"name":"A. John Rush","orcid":"0000-0003-2004-2382","position":15,"is_corresponding":false},{"id":70828,"name":"Mark A. Frye","orcid":"0000-0001-6997-4215","position":16,"is_corresponding":false},{"id":58339,"name":"Boadie W. Dunlop","orcid":"0000-0002-4653-0483","position":17,"is_corresponding":false},{"id":270363,"name":"Richard M. Weinshilboum","orcid":"0000-0002-4911-7985","position":18,"is_corresponding":false},{"id":75183,"name":"Rima Kaddurah‐Daouk","orcid":"0000-0003-1858-5732","position":19,"is_corresponding":false},{"id":244569,"name":"Siamak MahmoudianDehkordi","orcid":"0000-0002-6843-1718","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-18T23:14:33.640077Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}