title: Curcumin and major depression: a randomised, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict treatment response and antidepressant mechanisms of change.
abstract: A recent randomised, double-blind, placebo controlled study conducted by our research group, provided partial support for the efficacy of supplementation with a patented curcumin extract (500 mg, twice daily) for 8 weeks in reducing depressive symptoms in people with major depressive disorder. In the present paper, a secondary, exploratory analysis of salivary, urinary and blood biomarkers collected during this study was conducted to identify potential antidepressant mechanisms of action of curcumin. Pre and post-intervention samples were provided by 50 participants diagnosed with major depressive disorder, and the Inventory of Depressive Symptomatology self-rated version (IDS-SR30) was used as the primary depression outcome measure. Compared to placebo, 8 weeks of curcumin supplementation was associated with elevations in urinary thromboxane B2 (p<0.05), and substance P (p<0.001); while placebo supplementation was associated with reductions in aldosterone (p<0.05) and cortisol (p<0.05). Higher baseline plasma endothelin-1 (rs=-0.587; p<0.01) and leptin (rs=-0.470; p<0.05) in curcumin-treated individuals was associated with greater reductions in IDS-SR30 score after 8 weeks of treatment. Our findings demonstrate that curcumin supplementation influences several biomarkers that may be associated with its antidepressant mechanisms of action. Plasma concentrations of leptin and endothelin-1 seem to have particular relevance to treatment outcome. Further investigations using larger samples sizes are required to elucidate these findings, as the multiple statistical comparisons completed in this study increased the risk of type I errors.
authors.affiliation: School of Psychology and Exercise Science, Murdoch University, Perth, Western Australia 6150, Australia. Electronic address: a.lopresti@murdoch.edu.au.
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Lopresti
authors.affiliation: Impact Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia; Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
authors.affiliation: Brainlabs B.V., Deventer, The Netherlands.
authors.forename: Marc J M
authors.initials: MJ
authors.lastname: Meddens
authors.affiliation: School of Veterinary and Life Sciences, Murdoch University, Perth, Western Australia 6150, Australia.
authors.forename: Garth L
authors.initials: GL
authors.lastname: Maker
authors.affiliation: Brainlabs B.V., Deventer, The Netherlands.
authors.forename: Eddy
authors.initials: E
authors.lastname: Arnoldussen
authors.affiliation: School of Psychology and Exercise Science, Murdoch University, Perth, Western Australia 6150, Australia.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Drummond
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism* / Q000652:urine; D003474:Curcumin / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012463:Saliva / Q000378:metabolism; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D003474:Curcumin
keywords: Biomarkers; Clinical trial; Curcumin; Depression; Turmeric