Depression breakthough: Major depressive disorder linked to major diseases

Summary: Major depressive disorder has been linked to at least 22 distinct diseases, including asthma, coronary heart disease, and an increased risk of E. coli infection.

Source: University of South Australia

Major depressive disorder – referred to colloquially as the ‘black dog’ – has been identified as a genetic cause for 20 distinct diseases, providing vital information to help detect and manage high rates of physical illnesses in people diagnosed with depression.

Assessing risk factors between depression* and 925 diseases, a study from the Australian Centre for Precision Health at the University of South Australia found a causal relationship between depression and a range of respiratory, heart and digestive diseases including: asthma, coronary heart disease, high cholesterol, oesophagitis, gastroenteritis, E. coli infections, and urinary system disorders.

UniSA researcher, Anwar Mulugeta, says understanding the relationship between depression and other diseases can reduce the incidence of comorbidities – the presence of one or more additional conditions occurring with a primary condition – and improve the lives of millions of people worldwide.

“Data shows that people living with serious mental diseases, like depression, have much higher rates of physical illness than those in the general population,” Mulugeta says.

“But until now, these studies have been complicated by the possibility of other confounding factors, or even reverse causation where the physical condition is assumed to cause depression.

“This research puts the ‘chicken and egg’ conundrum to rest, showing that depression causes disease, rather than only the other way around.

“Importantly, this research signals that an individual diagnosed with depression should now also be screened for a defined set of possible comorbidities, enabling much better clinical management and significantly improved outcomes.”

Published in Molecular Psychiatry, the study is the first to use MR-PheWAS analyses to screen for a causal link between depression and a range of diseases. MR-PheWAS is a method that uses genetic data to explore causal associations between a risk factor (depression) and a range of disease outcomes. In this study, researchers assessed data from 337,536 UK Biobank participants to confirm the range of diseases affected by depression.

This study was led by Professor Elina Hyppönen, Director of the Australian Centre for Precision Health, who says appreciating the link between depression and distinct comorbidities has important implications for individuals, practitioners and policymakers.

“Today, nearly half of the population is estimated to experience a mental health condition in their lifetime,” Prof Hyppönen says.

“Understanding the connections between depression and other diseases is critical to ensure people with depression receive the support they require. The more we can look at the individual patient as a whole, the better their outcomes are likely to be.

“Our results suggest that it is important to look beyond the obvious, and that we need to screen and effectively manage depression-related comorbidities if we want to minimise the longer-term negative implications on health.

This shows a depressed looking woman

“It’s also important to focus on diet and encourage healthy lifestyles in this context. It was concerning to see that depression was associated with multiple inflammatory and even haemorrhagic gastro-intestinal complications, which may be due to side effects from medications used to treat depression, or even due to the greater occurrence of e-coli infections, both of which could be prevented.

“Through this study we provide critical evidence to help navigate the complexities of depression and its comorbidities, with the ultimate goal of delivering customer-centric treatment strategies for people suffering from this debilitating disease.”


* Depression is a common illness with more than 300 million people affected worldwide. It is the leading cause of ill health and disability worldwide, with more than half of the costs of depression directly or indirectly related to comorbidities. The economic burden of depression in Australia is more than $9.1 billion each year.


University of South Australia
Media Contacts:
Annabel Mansfield – University of South Australia
Image Source:
The image is in the public domain.

Original Research: Closed access
“Association between major depressive disorder and multiple disease outcomes: a phenome-wide Mendelian randomisation study in the UK Biobank”. Anwar Mulugeta, Ang Zhou, Catherine King & Elina Hyppönen.
Molecular Psychiatry. doi:10.1038/s41380-019-0486-1


Association between major depressive disorder and multiple disease outcomes: a phenome-wide Mendelian randomisation study in the UK Biobank

Depression affects all aspects of an individual’s life but evidence relating to the causal effects on health is limited. We used information from 337,536 UK Biobank participants and performed hypothesis-free phenome-wide association analyses between major depressive disorder (MDD) genetic risk score (GRS) and 925 disease outcomes. GRS–disease outcome associations passing the multiple-testing corrected significance threshold (P < 1.9 × 10−3) were followed by Mendelian randomisation (MR) analyses to test for causality. MDD GRS was associated with 22 distinct diseases in the phenome-wide discovery stage, with the strongest signal observed for MDD diagnosis and related co-morbidities including anxiety and sleep disorders. In inverse-variance weighted MR analyses, MDD was associated with several inflammatory and haemorrhagic gastrointestinal diseases, including oesophagitis (OR 1.32, 95% CI 1.18–1.48), non-infectious gastroenteritis (OR 1.25, 95% CI 1.06–1.48), gastrointestinal haemorrhage (OR 1.26, 95% CI 1.11–1.43) and intestinal E.coli infections (OR 3.24, 95% CI 1.74–6.02). Signals were also observed for symptoms/disorders of the urinary system (OR 1.36, 95% CI 1.19–1.56), asthma (OR 1.23, 95% CI 1.06–1.44), and painful respiration (OR 1.28, 95% CI 1.14–1.44). MDD was associated with disorders of lipid metabolism (OR 1.22, 95% CI 1.12–1.34) and ischaemic heart disease (OR 1.30, 95% CI 1.15–1.47). Sensitivity analyses excluding pleiotropic variants provided consistent associations. Our study indicates a causal link between MDD and a broad range of diseases, suggesting a notable burden of co-morbidity. Early detection and management of MDD is important, and treatment strategies should be selected to also minimise the risk of related co-morbidities.

Gut microbes influence severity of intestinal parasitic infections … › releases › 2018/03

Mar 9, 2018 – A new study indicates that the kinds of microbes living in the gut influence the severity and recurrence of parasitic worm infections in developing countries. The findings suggest that manipulating the gut’s microbial communities may protect against intestinal parasites, which …
The Parasite Ate Your Depression | Psychology Today › blog › evolutionary-psychiatry › the-…

May 26, 2011 – Parasites and commensal organisms may be essential for our immune …. The health of the human gut microbiome has been shown to impact …
Anxiety? Depression? Is Your Gut Microbiome to Blame? | Viome › blog › anxiety-depression-your-gut-microbiome…

Jun 12, 2018 – Your Gut Microbiome – The Missing Link In Anxiety and Depression … gut include bacteria, viruses, yeast, parasites, fungi, bacteriophages and …
Reconceptualizing major depressive disorder as an infectious disease › pmc › articles › PMC4215336

by T Canli – ‎2014 – ‎Cited by 29 – ‎Related articles

Oct 21, 2014 – I suggest that major depression may result from a parasitic, bacterial, ….. Mind-altering microorganisms: the impact of the gut microbiota on …

Abstract · ‎Background · ‎Conclusions
From gut dysbiosis to altered brain function and mental illness – NCBI › pmc › articles › PMC4879184

by GB Rogers – ‎2016 – ‎Cited by 241 – ‎Related articles

Apr 19, 2016 – Major depressive disorder (MDD) is typified by markers known to be influenced by the microbiome. For example, depression-associated …

Missing: parasites ‎| Must include: parasites
How parasites and bacteria could be changing the … – The Conversation › how-parasites-and-bacteria-could-be-changing-the-…

Jan 25, 2017 – This parasite can’t complete its lifecycle in humans, but we can be infected … But it was recently shown that the gut microbes that break down food … anxiety or depression by administering a “healthy” microbiome, and recent …
Are the bacteria/parasites in your gut affecting your thinking … › posts › are-the-bacteria-parasites-in-your-gut…

Jun 9, 2012 – When oral antibiotics were discontinued, bacteria in the gut returned to … factor (BDNF), which has been linked, to depression and anxiety.
Could You Fight Off Worms? Depends on Your Gut Microbes : Goats … › sections › goatsandsoda › 2018/04/07 › could-you-fig…
Apr 7, 2018 – Nearly 25 percent of people are infected with worms. New research suggests that gut microbes may be able to help in waging war against the …

Missing: depression ‎| Must include: depression
Microbiota and parasites | | › … › Medical Advances › Research in the news

Nov 13, 2018 – Changes in our gut bacteria have been implicated in several mental health disorders, such as schizophrenia and depression, but it’s unclear …
How parasites and bacteria could be changing the … – The Independent › LIFE › PULSE › Healthy Living

Jan 30, 2017 – Parasites could play a role in a range of illnesses, including dementia ….. anxiety or depression by administering a “healthy” microbiome, and …