Depression
HAM-D or BDI score
Major depressive disorder, or symptom severity on a named scale such as HAM-D or BDI. A bad week and a memory-task score are different objects.
SMILE used a structured interview plus Hamilton and Beck scores. Brush tracked symptom change in young adults with major depression. Yu required a diagnosis, ongoing medication, and a BDI above 9. Attention and memory tasks sit with cognitive performance. Rank motives sit with status seeking.
Also called major depression, MDD, depressive symptoms, HAM-D.
Connected relationships
Mendelian randomization · Contested
Alcohol intake→Depression
Higher Alcohol intake moves Depression only in some conditions. Read the mechanism.
Three Mendelian randomization files of alcohol on depression disagree: two ADH variants in 68,486 Copenhagen adults are null for antidepressant use, UK Biobank beer and spirits instruments raise major depression until insomnia and smoking enter the model, and ALDH2 plus ADH1B in 476 Chinese adults point the other way.
Randomized trial · Contested
Creatine supplementation→Depression
Higher Creatine supplementation moves Depression only in some conditions. Read the mechanism.
Toniolo 2019 found that 6 g a day of creatine monohydrate as an add-on for six weeks did not beat placebo on the change in Montgomery-Åsberg score among 35 people already treated for a bipolar depressive episode (P=0.560), while a secondary remission cut (score of 12 or less) favored creatine (52.9 percent versus 11.1 percent).
Randomized trial · Contested
Curcumin supplementation→Depression
Higher Curcumin supplementation decreases Depression.
Lopresti 2015 found that 500 mg of curcumin twice a day versus placebo did not separate on the Inventory of Depressive Symptomatology in the first four weeks among 56 adults with major depression, then showed a group-by-time interaction from week 4 to week 8 (P=0.045). The authors call that partial support.
Randomized trial · Moderate
Aerobic exercise→Depression
Higher Aerobic exercise decreases Depression.
Prescribed walking or jogging reduced depression scores in randomized trials of people with major depression. The programs looked similar to sertraline. Against a placebo pill, SMILE II's HAM-D gap did not reach significance. A year later, assigned arm no longer predicted mood.
Randomized trial · Contested
GLP-1 receptor agonist→Depression
A rise in GLP-1 receptor agonist does not identify a change in Depression.
In 3,377 adults with overweight or obesity and no known major psychiatric illness, weekly semaglutide 2.4 mg did not raise PHQ-9 depression scores versus placebo (Wadden 2024). A later trial in major depression found no change in symptom severity.
Meta-analysis · Low
Job strain→Depression
Higher Job strain increases Depression.
Madsen 2018's IPD-Work pool of 120,221 employees found a 27 percent higher rate of first hospital-treated depression after job strain (HR 1.27, 1.04 to 1.55). In Smith 2012, 3,735 Canadians free of depression who reported a rise in psychological demands had later depression odds of 2.36. Nobody assigned the job.
Observational · Low
Loneliness→Depression
Higher Loneliness increases Depression.
Hysing 2026 followed 10,460 Norwegian university students: those in the highest fifth of a 2022 Three-Item Loneliness Scale score, against the lowest fifth, had more CIDI major depressive episodes a year later (relative risk 2.02 in women and 2.64 in men after age and baseline Hopkins symptoms).
Randomized trial · Contested
Magnesium supplementation→Depression
Higher Magnesium supplementation decreases Depression.
Tarleton 2017 found that 248 mg a day of elemental magnesium as chloride, versus no treatment, cut PHQ-9 scores by 6.0 points among 112 primary-care adults with mild-to-moderate depression in an open-label crossover (95% CI -7.9 to -4.2). Barragán-Rodríguez 2008 found a similar drop versus imipramine in 23 older adults with diabetes and low serum magnesium.
Randomized trial · Moderate
Mindfulness-based training→Depression
Higher Mindfulness-based training decreases Depression.
Ritvo 2021 found that online mindfulness-based CBT plus monthly psychiatry cut Beck depression scores by 8.54 points versus psychiatry alone in 45 young adults with major depression. Cladder-Micus 2019's MBCT add-on in chronic treatment-resistant depression missed on the IDS-SR in intention-to-treat and still raised partial remission.
Randomized trial · Contested
Omega-3 supplementation→Depression
Higher Omega-3 supplementation moves Depression only in some conditions. Read the mechanism.
Lespérance 2011 found that 1,200 mg a day of EPA-heavy fish oil versus sunflower oil missed the primary Inventory of Depressive Symptomatology contrast among 432 Canadian outpatients in a major depressive episode (adjusted difference 1.32, -0.20 to 2.84); a planned no-anxiety slice moved, and two later pilots of 60 and 61 people do not settle the sign.
Randomized trial · Contested
Probiotic supplementation→Depression
Higher Probiotic supplementation decreases Depression.
Kazemi 2020 found that eight weeks of Lactobacillus helveticus and Bifidobacterium longum lowered the Beck Depression Inventory from 17.39 to 9.1 versus 18.18 to 15.55 on placebo in 81 completers with major depression. Akkasheh 2016 saw a similar Beck drop in 40 people.
Randomized trial · Contested
Rhodiola→Depression
Higher Rhodiola moves Depression only in some conditions. Read the mechanism.
Mao 2015 found that twelve weeks of Rhodiola rosea extract did not beat placebo on Hamilton change among 57 adults with mild-to-moderate major depression (-5.1 versus -4.6; groups P=0.79). Darbinyan 2008 reported that SHR-5 at 340 or 680 mg a day did move Hamilton scores versus placebo in 89 people.
Randomized trial · Contested
St John's wort→Depression
A rise in St John's wort does not identify a change in Depression.
The Hypericum Depression Trial (Davidson 2002) found that LI-160 St John's wort did not beat placebo on eight-week Hamilton change among 340 US outpatients with major depression and a baseline score of at least 20 (-8.68 versus -9.20, P=0.59). Sertraline, the active comparator, also missed that primary.
Randomized trial · Moderate
Sleep duration and regularity→Depression
A rise in Sleep duration and regularity does not identify a change in Depression.
In 126 adults with insomnia and major depression, adding internet CBT for insomnia to CBT for depression improved the insomnia score but not the depression score versus depression treatment plus a placebo sleep module.
Randomized trial · Moderate
Resistance training→Depression
Higher Resistance training decreases Depression.
Eight weeks of twice-weekly supervised resistance training lowered QIDS scores versus wait-list in 55 young adults. Depression was a secondary read of two anxiety-primary randomized trials.
Randomized trial · Moderate
25-hydroxyvitamin D→Depression
A rise in 25-hydroxyvitamin D does not identify a change in Depression.
Okereke 2020 found that 2000 IU a day of vitamin D3 versus placebo did not change the risk of depression or clinically relevant depressive symptoms among 18353 adults aged 50 and older in VITAL-DEP (hazard ratio 0.97, 95% CI 0.87 to 1.09). Rahman 2023 then found the same null on PHQ-9 in D-Health.
Sources
- MK Wium-Andersen et al. (2016). Increased alcohol consumption as a cause of alcoholism, without similar evidence for depression: a Mendelian randomization study.
- C Zhu et al. (2020). Alcohol Use and Depression: A Mendelian Randomization Study From China.
- D Qiu et al. (2024). Associations between dairy and alcohol consumption and major depressive disorder in a mendelian randomization study.
- RA Toniolo et al. (2019). A randomized, double-blind, placebo-controlled, proof-of-concept trial of creatine monohydrate as adjunctive treatment for bipolar depression.
- AL Lopresti et al. (2015). Curcumin for the treatment of major depression: a randomised, double-blind, placebo controlled study.
- JA Blumenthal et al. (1999). Effects of exercise training on older patients with major depression.
- M Babyak et al. (2001). Exercise treatment for major depression: maintenance of therapeutic benefit at 10 months.
- JA Blumenthal et al. (2007). Exercise and pharmacotherapy in the treatment of major depressive disorder.
- CJ Brush et al. (2022). A randomized trial of aerobic exercise for major depression: examining neural indicators of reward and cognitive control as predictors and treatment targets.
- DJ Yu et al. (2023). Comparison of moderate and vigorous walking exercise on reducing depression in middle-aged and older adults: A pilot randomized controlled trial.
- BM Hoffman et al. (2011). Exercise and pharmacotherapy in patients with major depression: one-year follow-up of the SMILE study.
- JA Blumenthal et al. (2021). The role of comorbid anxiety in exercise and depression trials: Secondary analysis of the SMILE-II randomized clinical trial.
- TA Wadden et al. (2024). Psychiatric Safety of Semaglutide for Weight Management in People Without Known Major Psychopathology: Post Hoc Analysis of the STEP 1, 2, 3, and 5 Trials.
- S Badulescu et al. (2026). Semaglutide for the treatment of cognitive dysfunction in major depressive disorder: A randomized clinical trial.
- IEH Madsen et al. (2018). Job strain as a risk factor for clinical depression: systematic review and meta-analysis with additional individual participant data.