Cohort profile: Cell-omics Resource of the Australian Genetics of Depression Study (AGDS:Cell-o)

Purpose: Major depressive disorder (MDD) is recognised to be phenotypically heterogeneous, yet subtyping based on clinical features has remained elusive. Here, we investigate heterogeneity by antidepressantusage according to prescription records. We describe a new cohort, the Cellomics Resource of the Australian Genetics of Depression Study (AGDS:Cello), established to allow integration of individual differences in symptom and genetic profiles with cellbased assays. Participants: The study participants had previously enrolled in the AGDS (2016 to 2019). Briefly, AGDS recruited 22,263 people who selfidentified as having lifetime depression. Participants completed detailed online questionnaires (445 questions) which allowed diagnosis of lifetime MDD and characterisation of many other sociodemographic and clinical factors.14,471 AGDS participants consented to linkage with prescription data (Australian Pharmaceutical Benefits Scheme; 4.5 years July 2013 to December 2017). These participants were allocated to one of seven mutually exclusive groups based on their monthly prescription patterns. Four groups were defined based on sustained use of specific antidepressants: sertraline, escitalopram or citalopram, desvenlafaxine or venlafaxine, duloxetine. Two groups represent more difficulttotreat depression (DTD) where participants showed no sustained dispensing of a single antidepressant: one was defined by selfreported treatment (or recommended treatment) with electroconvulsive therapy and the other by augmentation of antidepressants with either lithium or antipsychotics. The seventh group had selfreported diagnosis of bipolar disorder as well as prescription history of lithium. In 2023 to 2025 a subset of AGDS participants were invited to enrol in AGDS:Cello selected based on their antidepressant group membership. Participants were blinded to their group assignment and, if they consented to participate, completed detailed questionnaires about their symptoms, how medication changed their symptoms, and medication side effects. Findings to date: Of 9,965 AGDS participants with an MDD diagnosis, at least one prescription record of antidepressants, genomewide genotype data and of inferred European ancestry, 5,762 (58%) could be allocated to one of the seven antidepressant use groups. Of 3,107 people invited to view our AGDS:Cello website, 713 consented to participate in the study (to date). The selfreported antidepressant usage of these participants were compared to their prescription group; there was good consistency despite there being ~7 years between the prescription records used to make the groups and recruitment into AGDS:Cello. This is an interim report based on questionnaire data available to July 31 2025; the report will be updated when the study recruitment is closed (October 1 2025). Future plans: Participants provided blood samples which were processed to harvest peripheral blood mononuclear cells (PBMCs) to allow lymphoblastoid cell line (LCL), induced pluripotent stem cell (iPSC), assembloid or organoid studies. We plan to collect cell-based biological measures representing the genomes of AGDS:Cello participants which can be associated with a breadth of selfreported measures collected in the AGDS baseline and followup questionnaires and the AGDS:Cello questionnaire.