Why do people with mental health conditions like depression, schizophrenia, or anorexia often face higher risks of heart disease, diabetes, or other physical health problems?
Part of the answer lies in lifestyle and the side effects of medications. But new research led by Dr Dylan Kiltschewskij, from the University of Newcastle and HMRI’s Precision Medicine and Health research program, suggests there may be something deeper at play: an inherent link written into our genes.
Dr Dylan Kiltschewskij
The study, published in international journal Molecular Psychiatry, built a ‘genetic atlas’ linking ten major mental health conditions to hundreds of blood-based metabolites. These metabolites range from dietary fats to blood sugars and amino acids. Using the largest genetic datasets available, with up to two million participants, the researchers asked do these blood metabolites share underlying biology with mental health, and do they play a causal role?
Metabolism and the mind
Mental health conditions are not exclusively illnesses of the brain and mind.
“People living with conditions like depression and schizophrenia often also develop metabolic problems such as obesity, diabetes, or abnormal cholesterol levels,” Dr Kiltschewskij says.
“This contributes to poorer physical health, predisposes individuals to heart disease and greatly contributes to shorter life expectancy compared to people without a mental health condition.”
Traditionally, these connections have been explained by non-genetic factors such as unhealthy diets, reduced exercise, barriers to health care and the side effects of medications. But emerging genetic studies have shown that mental and metabolic health share common biological roots that could open new avenues for diagnosis, treatment and prevention.
What the research found
By combining large-scale genetic data on 249 metabolites with 10 mental health conditions, 1,100 significant connections were observed. These connections were uncovered through genetic markers, specifically tiny changes in the DNA sequence, that are shared between some metabolites and mental health conditions.
“As an example, we found that some fatty acids shared genetic signatures with schizophrenia, potentially indicating there are common biological pathways influencing both,” Dr Kiltschewskij says.
“While these correlations suggest shared biology we need to dig deeper to confirmcausation.”
Exploring causality
To test for causality, researchers would normally need to conduct a randomised controlled trial, where participants randomly receive a treatment or a placebo to determine if a metabolite is beneficial for mental health. However, this is time consuming, costly, and not scalable across the breadth of metabolites that were identified.
To overcome these challenges, Dr Kiltschewskij says he used complex statistics to mimic a clinical trial using genetics.
“Instead of randomly giving participants a treatment or a placebo, we look at genetic markers that control blood levels of certain metabolites, exploiting the fact that these are randomly distributed in the population.”
In doing so, the research found evidence for some metabolites causally influencing mental health, including:
High-density lipoproteins (HDL, or “good cholesterol”) and anorexia nervosa
We found evidence that certain aspects of HDL (e.g. size, lipid content) may increase the risk of anorexia. This adds a genetic layer to previous clinical findings that people with anorexia often have unusually high HDL levels.
Low- and very low-density lipoprotein (LDL / VLDL, or “bad cholesterol”), depression, and PTSD
Some of these metabolites were linked to higher or lower risk of these conditions.
Omega-3 fatty acids and ADHD
We found genetic evidence that omega-3 fats, including DHA (docosahexaenoic acid), may play a protective role, echoing previous clinical trials showing some individuals benefit from omega-3 supplementation.
Shared genetic signatures between these metabolites and brain structure were also found. For example, lipids associated with depression and ADHD were also linked to differences in thickness of the cerebral cortex, hinting at a possible pathway from metabolism to brain biology to mental health conditions.
Why this matters
This work highlights specific blood-based metabolites that may serve as biomarkers, measurable traits that help predict risk or guide treatment. Importantly, Dr Kiltschewskij says, many metabolites are clinically actionable, meaning they can be influenced through diet, lifestyle or existing medications.
“For instance, if omega-3 fatty acids are protective for ADHD, or if specific lipid traits contribute to depression or PTSD, this opens the door for new approaches to prevention and therapy. Similarly, identifying lipids linked to anorexia could help develop better screening tools or interventions.”
Looking ahead
Of course, these findings don’t mean we should all rush to change our diets or cholesterol levels. Genetic studies point towards potential biological mechanisms, but clinical trials are needed to confirm whether targeting these pathways can improve mental health.
Still, the message is clear: the mind and body are deeply intertwined, and by studying them together, new ways of reducing the heavy burden of psychiatric illness may be discovered.