First-episode mild depression in young adults is a pre-proatherogenic condition even in the absence of subclinical metabolic syndrome: lowered lecithin-cholesterol acyltransferase as a key factor

Background: Major depression is classified into distinct subtypes: simple (SDMD) and major dysmood disorder (MDMD). MDMD patients exhibit elevated atherogenicity and decreased reverse cholesterol transport (RCT). However, comprehensive data regarding lipid metabolism is absent in first episode (FE)-SDMD. Objectives: In this case-control study, plasma lipid levels, lecithin-cholesterol acyltransferase (LCAT), free cholesterol, ApoA1, ApoB, and ApoE are compared between academic students with first episode SDMD (FE-SDMD) (n=44) or SDMD (n=64) and control students (n=44), after excluding those with metabolic syndrome (MetS). Results: LCAT is decreased, and free cholesterol and ApoE increased in subjects with SDMD and FE-SDMD as compared with controls. There were no significant alterations in high-density lipoprotein cholesterol (HDLc), apolipoprotein (Apo)A1, RCT, ApoB and triglycerides in SDMD. LCAT, free cholesterol and atherogenicity indices are significantly associated with suicidal behaviors and the SDMD phenome. The effects of LCAT on those phenome features is completely mediated by free cholesterol and brooding. SDMD and FE-SDMD patients without signs of subclinical MetS show lowered LCAT and increased free cholesterol as compared with normal controls. There are significant interactions between the SDMD and FE-SDMD diagnosis and subclinical MetS, which result in decreased HDLc and RCT, and an increased ApoB/ApoA ratio. Discussion: FE-SDMD and SDMD are pre-proatherogenic states, because of decreased LCAT, and increased free cholesterol and ApoE, and their intersections with subclinical MetS. These aberrations may drive atherogenicity, and activation of peripheral and central oxidative, neuro-immune, and degenerative pathways. Individuals with FE-SDMD should be screened for increased atherogenicity risk by measuring LCAT, free cholesterol and ApoE. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was supported by the 90th Anniversary of Chulalongkorn University Scholarship under the Ratchadaphisek Somphot Fund (Batch#47), and the Ratchadaphisek Somphot Fund (Faculty of Medicine), MDCU (GA65/17), Chulalongkorn University, Thailand, to AV; and the Thailand Science Research, and Innovation Fund at Chulalongkorn University (HEA663000016), and a Sompoch Endowment Fund (Faculty of Medicine) MDCU (RA66/016) to MM. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The research project (IRB no.351/63) was approved by the Institutional Review Board of Chulalongkorn University's institutional ethics board, Bangkok, Thailand, which follows the International Guideline for Human Research protection as required by the Declaration of Helsinki, The Belmont Report, CIOMS Guideline and International Conference on Harmonization in Good Clinical Practice (ICH-GCP). All participants signed the appropriate institutional informed consent forms before data collection. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes MM will reply to reasonable requests for the dataset used in the current study after it has been fully utilized by all authors.