World first study uncovers genetic link to post natal depression

Author: University Hospitals Coventry and Warwick

Date: Jul 2013

The first evidence of a genetic predisposition to post natal depression (PND) due to variants in genes of the hypothalamo-pitutitary-adrenal (HPA) axis has been discovered by a team of specialists at University Hospitals Coventry & Warwickshire NHS Trust (UHCW) and Warwick Medical School.

Research led by Professor Dimitris Grammatopoulos, Professor of Molecular Medicine and Consultant in Clinical Biochemistry and Molecular Diagnostics at UHCW and Warwick Medical School, has proven a genetic variation can lead to women becoming up to five times more likely to suffer from PND.

His paper, which has been published by the Journal of Psychiatric Research, was based on his recent study of 200 pregnant women. He and a team of specialists (Miss Neelam Engineer and Dr Steve Smith) from the Departments of Obstetrics and Biochemistry identified that an overwhelming majority of women who went on to develop PND had at least one of two molecular signatures – variations in a person’s DNA – which increase the risk of PND.

Up to 15% of women are reported to suffer from PND, yet medics believe this figure could be much higher as many severe cases of the ‘baby blues’ go unreported.

Previous studies have identified multiple molecular signatures linked to depression. Professor Grammatopoulos tested some of these variations and has now isolated two variations specifically linked to PND, which are triggered by hormonal imbalances during pregnancy.

During pregnancy, the HPA axis becomes disregulated due to increased levels of oestrogen. This can lead to higher levels of cortisol or increased sensitivity to hormones, which has been linked to depression. Usually the axis will recalibrate itself after delivery but, with some women, the axis cannot do so, leading to PND. It is not known why this happens, but the study suggests that this sensitivity might be genetically programmed.

Table 1: Genetic variations linked to depressive symptoms

The Edinburgh Post Natal Depression Score (EPDS), a 10 question survey which is currently the most commonly used means of diagnosing PND, was used to determine whether the symptoms were present during and after pregnancy throughout the research.

The team is now looking to demonstrate a link between the genetic variants, increased cortisol levels and PND – providing a biomarker to more accurately detect changes in HPA axis sensitivity in women with high genetic risk.

Professor Grammatopoulos said: “PND is a complex condition influenced by everything from a woman’s financial situation to the level of support she is given.

However, our research shows there is more to the baby blues than environmental factors alone and has a strong genetic component. This discovery has the potential to revolutionise our care for expectant mothers by screening them before the devastating symptoms of PND set in.

The team at UHCW aim to establish a three-step process for caring for pregnant women:

  1. DNA screening used to determine the genetic risk of PND
  2. A specific biomarker such as increased cortisol then used to identify changes in the HPA axis
  3. Tools such as the EPDS questionnaire used to correlate with symptoms of depression and genetic bio markers

Professor Grammatopoulos added: “At the moment, women only go to their GP once their symptoms are already severe. This new process will help identify, provide early support and if necessary, treatment, and even prevent the illness.

This innovative research can lead to development of a new patient pathway. This is a fantastic example of how personalised medicine can transform the way healthcare is delivered.

Professor Dimitris Grammatopoulos and his team at UHCW are now conducting the next phase of their research, recruiting approximately 1,500.

Women can still sign up for the next stage of research and can register their interest by emailing Professor Grammatopoulos and Miss Neelam Engineer: They must be pregnant with no current history of depression or other mental illness.

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Last revised: 2 July 2015

Next review: 2 July 2018