期刊
TRANSLATIONAL PSYCHIATRY
卷 12, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41398-022-02217-0
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资金
- Stanley Medical Research Institute [12608000475347]
- National Health and Medical Research Council (NHMRC) Australia [07TGF-1102]
- NHMRC Senior Research Fellowship [566529]
- Colonial Foundation [1080963, 1027532, 566593, 1060996]
- Irish Health Research Board research grant [HRB ILP POR 2019-005]
- Wellcome Trust Innovation Flagship Award
- Health Research Board (HRB) [220438Z/20/Z]
- Science Foundation Ireland (SFI) [HRB/HRA/PHR/2015-1293]
- European Regional Development Fund [16/RC/3948]
- FutureNeuro industry partners
The present study found a long-term association between omega-3 polyunsaturated fatty acids (PUFAs) and changes in complement and coagulation proteins in the blood. Increasing omega-3 PUFAs can alleviate symptom severity and improve cognition in individuals at clinical high risk through modulating effects of complement and coagulation proteins.
Preliminary evidence indicates beneficial effects of omega-3 polyunsaturated fatty acids (PUFAs) in early psychosis. The present study investigates the molecular mechanism of omega-3 PUFA-associated therapeutic effects in clinical high-risk (CHR) participants. Plasma samples of 126 CHR psychosis participants at baseline and 6-months follow-up were included. Plasma protein levels were quantified using mass spectrometry and erythrocyte omega-3 PUFA levels were quantified using gas chromatography. We examined the relationship between change in polyunsaturated PUFAs (between baseline and 6-month follow-up) and follow-up plasma proteins. Using mediation analysis, we investigated whether plasma proteins mediated the relationship between change in omega-3 PUFAs and clinical outcomes. A 6-months change in omega-3 PUFAs was associated with 24 plasma proteins at follow-up. Pathway analysis revealed the complement and coagulation pathway as the main biological pathway to be associated with change in omega-3 PUFAs. Moreover, complement and coagulation pathway proteins significantly mediated the relationship between change in omega-3 PUFAs and clinical outcome at follow-up. The inflammatory protein complement C5 and protein S100A9 negatively mediated the relationship between change in omega-3 PUFAs and positive symptom severity, while C5 positively mediated the relationship between change in omega-3 and functional outcome. The relationship between change in omega-3 PUFAs and cognition was positively mediated through coagulation factor V and complement protein C1QB. Our findings provide evidence for a longitudinal association of omega-3 PUFAs with complement and coagulation protein changes in the blood. Further, the results suggest that an increase in omega-3 PUFAs decreases symptom severity and improves cognition in the CHR state through modulating effects of complement and coagulation proteins.
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