How our genes affect stress response

South Australian researchers are leading an international effort to determine how our genetic make-up affects our responses to stressful situations and the likelihood that this will lead to major depressive disorder (MDD).

The South Australian Health and Medical Research Institute’s (SAHMRI) Mind and Brain Theme has identified a particular gene that appears to indicate individuals who are more likely to cope so poorly with stress that it leads to clinical depression.

Professor Ma-Li Wong of Flinders University said, “We have obtained animal data that support this concept, and it provides a possible brain pathway that explains it.”

Over 40% of mental illness disability is linked to depressive disorders — the second most common form of ongoing disability after lower back pain. Major depressive disorder affects around 3.5% of the global population, with rates reaching as high as 15% in the developed world. Almost 60% of people who die by suicide have reported incidences of MDD.

Part of an international collaboration, the current research was published in Molecular Psychiatry and drew on initial analysis of a Mexican-American sample population. That research determined that genetic variations of the PHF-21B gene could increase the risk of depression.

Professor Wong explained: “By taking a DNA sample, analysing it for rare gene variants that cause change in the amino acid sequence of proteins and comparing the genetic data from many people without depression with those with depression, we can figure out whether the function of some genes could be related to increased risk for depression.”

The second population analysed was a European and Australian sample that Professor Bernhard Baune of the University of Adelaide contributed. Amongst this group only rare variations on the PHF-21B gene were linked to increased risk of MDD.

Professor Wong, who is the Senior Principal Research Fellow and Head of the Pharmacogenomics Research Program at SAHMRI, said: “Variants of the PHF-21B gene contribute significantly to differences in the levels of expression of this gene in several brain areas, including the hippocampus, which is a brain region important in regulating a person’s mood and stress response. Therefore, this gene could help modulate our mood and reaction to stress.”

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