Depression is the leading cause of disability worldwide and is associated with a 10-year reduction in life expectancy.^1,2 Achieving and maintaining remission, the goals of treatment for this recurrent disease, improves functioning, reduces suicide risk, and leads to greater clinical stability.³ Patients who have not responded to at least 2 different antidepressants in the current depressive episode are considered to have treatment-resistant depression (TRD).⁴ Patients with treatment-resistant major depressive disorder (MDD) experience relapse at a higher rate than do those with treatment-responsive MDD. Even when patients with TRD respond to treatment, the overall relapse rate while continuing treatment with the same antidepressant is high after 2 (65%; within 3.1 months) and 3 failed trials (71.1%; within 3.3 months).³ There is a substantial unmet need for effective treatments that can sustain antidepressant benefits for the population with TRD.

Some studies have pointed out that several dietary patterns could be associated with a reduced risk of depression among adults. This association seems to be consistent across countries, cultures and populations. The objective of the study was to compare and to establish the type of relationship between three diet quality scores and depression in the SUN (Seguimiento Universidad de Navarra) Cohort study. We performed a dynamic cohort study based on Spanish university graduates free of depression at baseline. Dietary intake was repeatedly assessed at baseline and after 10 years of follow-up with a validated semi-quantitative food-frequency questionnaire. Three previously described diet quality scores: Mediterranean Diet Score (MDS), Pro-vegetarian Dietary Pattern (PDP) and Alternative Healthy Eating Index-2010 (AHEI-2010) were built. Participants were classified as having depression if they reported a new clinical diagnosis of depression by a physician or initiated the use of an antidepressant drug during follow-up. Time-dependent Cox regression models with cumulative averages of diet and restricted cubic splines were used to estimate hazard ratios of depression according to quintiles of adherence to the MDS, PDP and AHEI-2010. One thousand and fifty one incident cases of depression were observed among 15,093 participants from the SUN Cohort after a median follow-up of 8.5 years. Inverse and significant associations were observed between the three diet quality scores and depression risk. The hazard ratios and 95 % confidence intervals for extreme quintiles (fifth versus first) of updated adherence to MDS, PDP and AHEI-2010 were 0.84 (0.69–1.02), 0.74 (0.61–0.89) and 0.60 (0.49–0.72), respectively. The dose–response analyses showed non-linear associations, suggesting that suboptimal adherence to these dietary patterns may partially be responsible for increased depression risk. Better adherence to the MDS, PDP and AHEI-2010 was associated with a reduced risk of depression among Spanish adults. However, our data suggested a threshold effect so that although the risk of depression was reduced when comparing moderate versus lower adherence, there was not much extra benefit for the comparison between moderate and high or very high adherence.