Ziogas, A. | Search bioRxiv

bioRxiv2023

Fatty acid desaturation and lipoxygenase pathways support trained immunity

Infections and vaccinations can induce long-term enhanced responses of innate immune cells to heterologous stimuli, establishing a de facto innate immunological memory termed trained immunity. Monocytes exposed to the Bacillus Calmette-Guerin (BCG) vaccine, have a trained immunity phenotype, characterized by an increased biosynthesis of different lipid mediators (LMs) derived from long-chain polyunsaturated fatty acids (PUFAs). Pharmacological and genetic approaches showed that long-chain PUFA synthesis and lipoxygenase (LOX)-derived LMs are crucial for the BCG trained immunity responses of human monocytes. Furthermore, monocytes of healthy individuals vaccinated with BCG are enriched in 12-LOX products. The elucidation of the lipid metabolic pathways that promote innate immune memory contributes to our understanding of trained immunity and may help identify therapeutic tools and targets for the modulation of innate immune responses.

immunology↗

bioRxiv2023

Emotion-induced frontal α asymmetry predictsrelapse after discontinuation of antidepressantmedication

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSOne in three patients relapse after antidepressant discontinuation. Thus, the prevention of relapse after achieving remission is an important component in the long-term management of Major Depressive Disorder (MDD). However, no clinical or other predictors are established. Frontal reactivity to sad mood as measured by fMRI has been reported to relate to relapse independently of antidepressant discontinuation and is an interesting candidate predictor. MethodsPatients (n=56) who had remitted from a depressive episode while taking antidepressants underwent EEG recording during a sad mood induction procedure prior to gradually discontinuing their medication. Relapse was assessed over a six-months follow-up period. 35 healthy controls were also tested. Current source density of the EEG power in the band (8-13Hz) was extracted and alpha-asymmetry was computed by comparing the power across two hemispheres at frontal electrodes (F5 and F6). OutcomesSad mood induction was robust across all groups. Reactivity of -asymmetry to sad mood did not distinguish healthy controls from patients with remitted MDD on medication. However, the 14 (25%) patients who relapsed during the follow-up period after discontinuing medication showed significantly reduced reactivity in -asymmetry compared to patients who remained well. This EEG signal provided predictive power (69% out-of-sample balanced accuracy). InterpretationA simple EEG-based measure of emotional reactivity may have clinical utility in the management of antidepressant discontinuation. FundingSwiss National Science Foundation project grant 320030L_153449 / 1 to QJMH, Stiftung Deutsche Depressionshilfe to HW and QJMH, a Deutsche Forschungsgemeinschaft (DFG) grant (WA 1539/5-1) to HW, EMDO Stiftung to QJMH and the Rene and Susanne Braginsky Foundation and Clinical Research Priority Programme "Molecular Imaging" at the University of Zurich to KES.

neuroscience↗