The heart of the matter: in search of causal effects of depression on somatic diseases

The question of whether depression is a causal factor in somatic diseases remains unanswered despite decades of research. In an extensive umbrella review of systematic reviews and meta-analyses, Machado et al. (BMC Medicine 16:112, 2018) found significant associations between depression and all-cause and cause-specific mortality. However, as the authors clearly argued, these results do not prove causation. The next logical step is to study the potential effect of depression and other mental disorders by placing emphasis on temporality (associations over time) and specificity (unique associations) of associations between a comprehensive set of mental disorders and somatic diseases. A data-driven approach in large samples could uncover disease development trajectories to provide a route for researchers and clinicians to improve medical outcomes in vulnerable patient groups.