Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Burden of Comorbidities in Major Depressive Disorder

There is a casual link between major depressive disorder (MDD) and a broad range or diseases, suggesting a burden of comorbidity, and new study found. Researchers used information from 337,536 UK Biobank participants and performed hypothesis-free phenome-wide association analyses between MDD genetic risk score (GRS) and 925 disease outcomes. They found:

  • MDD GRS was associated with 22 distinct diseases in the phenome-wide discovery stage, with the strongest signal observed for MDD diagnosis and related comorbidities including anxiety and sleep disorders.
  • In inverse-variance weighted Mendelian randomization (MR) analyses, MDD was associated with several inflammatory and hemorrhagic gastrointestinal diseases.
  • Signals were also observed disorders of the urinary system, asthma, and painful respiration.
  • MDD was associated with disorders of lipid metabolism and ischemic heart disease.


Mulugeta A, et al. Association between major depressive disorder and multiple disease outcomes: a phenome-wide Mendelian randomization study in the UK Biobank. [Published online ahead of print August 19, 2019]. Mol Psychiatry. doi: 10.1038/s41380-019-0486-1.


The study by Mulegeta et al. is an interesting approach that attempts to determine which medical diseases are not only associated with major depressive disorder (MDD) but also may be caused by MDD itself. In other words, the authors feel that MDD may be a disorder that causes esophagitis, gastroesophageal reflux disorder, asthma, hypercholesterolemia, and others. They point out that patients treated with serotonergic antidepressants will have more tendency towards bleeding (a known side effect) and this may confound the esophagitis finding. Keeping this confound in mind, having MDD likely means you are on an antidepressant and the latter could be the causative agent. Regardless, psychiatrists may want to increase monitoring of MDD patients for these other medical conditions if these typically primary care-oriented patient complaints are noted in psychiatric sessions. —Thomas L. Schwartz, MD; Senior Associate Dean of Education, Interim Chair/Professor of Psychiatry, SUNY Upstate Medical University.