Faulty gene linked to asthma, diabetes and depression

According to the World Health Organization, over 350 million people suffer from depression, making it the single largest cause of disability worldwide.

Identifying a single biological cause for depression has proved elusive, but researchers from the University of Adelaide have found a physiological link between asthma, heart disease and depression that all leads back to a single faulty gene.

Pouring over thousands of peer-reviewed studies, a team from the university’s Discipline of Psychiatry has found a faulty gene — PXMP2 — that is linked to cardiovascular and metabolic conditions, supporting a hypothesis that depression and cardiovascular diseases may share molecular pathways.

“With the shared pathways between cardiovascular disorders and depression, we suggest that faulty regulation of the PXMP2 gene may play a role in depressive disorders via specific metabolic pathways,” said the paper’s lead author, Professor Bernhard Baune. “Depression is much more complex than most people think, and it includes dysfunction at multiple biological levels, from genes to brain regions, and blood circulating through the body.”

Professor Baune’s team re-analysed a wealth of existing data, concentrating on the genes that appeared in multiple studies, identifying 57 differently expressed genes in the brain and 21 in the peripheral tissues. Professor Baune explained: “What we saw was overlap in genetic expression between the brain and peripheral tissues that strongly implicated a link between depression and cardiovascular disease.

“Our research on genetic networks also showed support for the wide range of theories that different genes may play a role in depression, including those involved in regulation of serotonin, melatonin and the immune system, among many others. Even so, PXMP2 represents a very strong, new target for future research programs.”

It has long been known that there is a high incidence of comorbidity between depression and chronic somatic diseases including diabetes, asthma and cardiovascular disease. This research supports the hypothesis of overlapping mechanisms involved in the pathophysiology of these non-psychiatric diseases and depression.

“PXMP2 is robustly expressed during depression,” said Professor Baune. “However, to the best of our knowledge, neither this faulty gene in particular nor its related functions in metabolism have ever been investigated in relation to mood disorders of any kind.”

This research has been funded by the National Health and Medical Research Council (NHMRC) and will appear in the journal Neuroscience & Biobehavioral Reviews.

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