DMT and harmine responses in monocyte-derived microglia- like cells from patients with treatment-resistant depression
Year: 2026
Type: preprint
Abstract: Purpose To examine cytokine, surface-marker, and morphological responses to N, N-dimethyltryptamine (DMT) and harmine in lipopolysaccharide (LPS)-challenged monocyte-derived microglia-like cells (iMGs) from patients with treatment-resistant depression (TRD). Methods This exploratory study used assay-specific subsets of a cohort of four healthy controls and seven patients with TRD. The principal pharmacological assays used TRD-derived iMGs. Parallel cultures were compared under control conditions, LPS alone (100 ng/mL, 24 h), or LPS followed by DMT (90 µg/mL) or harmine (35 µM) for 3 h. Cytokine transcripts and surface-marker positivity were evaluated in four donors, and high-content imaging in three. Results DMT increased IL10 expression relative to LPS alone (mean difference, 0.4088; 95% confidence interval, 0.1546–0.6629; Tukey-adjusted p = 0.0134). LPS increased IL6 relative to control (adjusted p = 0.0305), whereas neither compound significantly reduced IL6 after adjustment. CD86 and CD200 positivity showed no significant condition effects. Process number showed an overall condition effect (exact Friedman p = 0.017), without significant drug-versus-LPS contrasts after Holm correction. Conclusion IL10 transcription is a candidate response measure for replication. Small donor samples, the absence of matched healthy-control pharmacological assays, and concentration-selection limitations prevent inference about disease specificity, generalized anti-inflammatory activity, or clinical efficacy.
Source: Research Square
Authors: Francisco Cid Coelho Pinto, Fátima Cássia Evangelista Oliveira, Hilda Tahim Souza, José Brito Vieira Neto, Isabelle de Fátima Vieira Camelo Maia, Sérgio André Souza Júnior, Fábio Oliveira Silva Ribeiro, Alyne Rodrigues Araujo Nobre, Claudio Costa dos Santos, Islay Lima Magalhães, Caio Andrade Oliveira, Deysi Viviana Tenazoa Wong, Claudia do Ó Pessoa, David Freitas Lucena, Maria Francilene Souza Silva, Danielle S. Macedo
Language: English
Subfield: Biological Psychiatry
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7225798354