The association between TNF-α and major depression, although the volume of existing research for this inflammation marker is equal to or even greater than that examining IL-6 or CRP, was less convincing: the overall effect size was smaller, the findings in sensitivity and subgroup analyses were less consistent and, importantly, the association was attenuated in higher quality studies and studies controlling for obesity. This evidence concerns the gene IL6 and obesity due to melanocortin 4 receptor deficiency.