Another methodological issue that can obscure and complicate

Another methodological issue that can obscure and complicate the assessment of the diet-mental health relationship relates to the covariance between health behaviours such as diet, physical activity and smoking. As these health behaviours are all associated with depression in a bidirectional manner, as well as being correlated with each other, teasing apart the relative contribution of each to the variance in depression and understanding how each interacts with each other can complicate the interpretation of the results of observational studies. As such, caution should be employed in such interpretation. Similarly, while sensitivity analyses and study design attempt to assess reverse causality (e.g. Jacka et al., 2015a) and residual and unmeasured confounding by other important factors, such as socioeconomic position (Jacka et al., 2014a), the limitations of observational study designs must always be recognised. Less commonly-utilized statistical approaches to data analysis, such as structural equation modeling, may help to mitigate some of the most pernicious issues relating to residual confounding in observational studies (Westfall and Yarkoni, 2016). Animal experiments also offer an important contribution to our understanding, as they rsk inhibitor allow for manipulation of diet in a controlled way; however, animal and human biology and nutritional needs differ substantially and the limitations here are also clear.
Intervention Data in Humans The European PREDIMED study (Estruch et al., 2013) represents the largest dietary intervention attempted to date. In this study, older adults with elevated risk factors for cardiac events were randomised to one of three dietary conditions: one of two forms of a Mediterranean diet or a ‘low fat’ control condition, based on American Heart Association dietary guidelines. Participants received individualised and group support for dietary change and adherence, as well as being provided with some relevant foods. The primary outcome of PREDIMED was cardiovascular events and the study was successful in showing that a Mediterranean diet could protect against such outcomes (Estruch et al., 2013). However, although not statistically powered to assess de novo depression as an outcome, post hoc analyses of the self-reported depression data from PREDIMED suggested a non-significant trend towards the prevention of depression by the Mediterranean diet supplemented with nuts (OR=0.78 (0.55–1.10)), and this was statistically significant in those with type 2 diabetes, who comprised approximately half the study sample (OR=0.59 (0.36–0.98)) (Sanchez-Villegas et al., 2013). In another randomised prevention trial, dietary coaching used as a control condition was unexpectedly equivalent to problem-solving therapy in both preventing clinical depression (Stahl et al., 2014) and improving health-related quality of life (Jimenez et al., 2015) in disadvantaged older Americans. While these preliminary findings suggest that dietary interventions or improvement may be useful for preventing depression, up until recently there were no rigorous intervention studies explicitly designed to take a dietary approach to treatment in populations with existing mental disorders (Opie et al., 2015a). We have now just published the first study to do so and the results are noteworthy. In the SMILES study (O\'Neil et al., 2013; Jacka et al., 2017) we aimed to investigate the efficacy of an adjunctive dietary improvement program for the treatment of major depressive episodes using a 12-week, parallel group, single blind randomised controlled trial design. The intervention comprised the ‘ModiMedDiet’, which is rich in vegetables, fruit and whole grains, with an emphasis on increased consumption of oily fish, extra virgin olive oil, legumes and raw unsalted nuts. However, in contrast to traditional Mediterranean diets, it advocates for moderate consumption of red meat (Jacka et al., 2012b) and dairy. Participants, most of whom were already receiving psychotropic medications and/or psychotherapy, received seven individual dietary coaching sessions of approximately 60min each, delivered by an accredited dietitian, and the control group received manualised social support (‘Befriending’) to the same schedule and intensity. The results were notable, with the intervention group demonstrating significantly greater improvement between baseline and 12weeks than the control group with a very large effect size (Cohen\'s d −1.16: 95% CI: −1.73, −0.59) and a number needed to treat (NNT) of 4.1 (Jacka et al., 2017). Secondary outcomes were also concordant with the primary outcome measure and all effects were independent of any changes in BMI, self-efficacy, smoking rates and/or physical activity. Finally, dietary adherence correlated strongly with improvements in mood. These results provide the first RCT evidence for dietary improvement as a treatment strategy for treating major depressive episodes, as well as providing intervention evidence supporting causality. Importantly, the study also tells us that working with patients with mental illness to help them to achieve dietary improvements is feasible, despite the fatigue and reduced motivation often associated with depression. On the other hand, the relatively small sample size and the inability to blind participants to group allocation are clear limitations to this study, which now requires replication using larger study samples.