Principal Investigator Prof. Veronica O’Keane
Research title: “A study of depression in late adolescents in Tallaght: Brain Imaging, stress systems and Response to treatment”
Meath Foundation research funding awarded 2013
If a pregnant woman is stressed, high cortisol can be transferred into the baby in utero while the baby’s brain is developing, with the result that babies born to depressed women may have dysregulated stress systems, Prof. Veronica O’Keane, TCD Professor of Psychiatry and Consultant Psychiatrist at Tallaght Hospital told the Symposium.
She presented work on The REDEEM Project – a collaboration among the Psychiatry and the Obstetric Services, the Children’s’ Hospitals and Trinity College Institute for neurosciences (TCIN) – which is examining the brain and stress systems during prenatal life and infancy; and also examining young adults with first onset depression.
The funding for the preliminary work came from the Meath Foundation and the project is now also funded by the HRB and the NCRC.
“We are looking at cortisol levels and inflammatory markers in depression in pregnant women and young adults who present for the first time with depression. We are also looking at epigenetics,” she said.
One of the reasons she became interested in the aetiology of depression was the inability to separate out a disease state from what happened to the individual.
“I became interested in how adversity in life predisposes one to depression, how it modifies your physiology so that the majority of people if exposed to sufficient adversity will become depressed. If you wonder if you are depressed or not, you are not because if you are it hits you like a rock. It is a very significant and distressing change in your emotion; it affects your sleep, appetite, motor activity, cognitive difficulties and can lead to suicidal ideation. These symptoms may not be present at all times and most of them can be “reversed” and still retain the definition of depression.
“I admitted a traveller in his 40s and he told me two of his brothers and three of his male first cousins had hanged themselves. Suicide is very prevalent in the traveller community. There are some travellers whose parents and grandparents have killed themselves through suicide.
“Stress is very central to depression. Our stress levels are always changing to cope with stressors and then return our bodies to a baseline level of stress: this is how we adapt to a changing environment. With depression the levels of cortisol, our main stress hormone which is controlled by the brain, does not go down in the evening. It remains high at all times, so depressed people don’t sleep.”
Prof. O’Keane said she became interested in the idea that memories of stressful events from our childhood were modifying our brains, so we were producing high cortisol levels at all times. Cortisol levels also suppressed inflammation but in the case of people who had been depressed for a long time cortisol stopped working on the inflammatory system.
“Our neuroimaging findings to date are as expected – the hippocampus is smaller in young depressed brains, probably because of stress that has been imposed on them. They have poorer cognitive activation during emotional tasks, their inflammatory system is not functioning.
“Patients exposed to high cortisol levels for a long time suffer brain cell death. We found that when patients were doing emotional tasks they had a difficulty in switching their brains from thinking about the emotional tasks to working things out, whereas non depressed people were able to drop the emotional aspect and move on to the task. Cortisol levels were high and flattened in depressed people, their cortisol levels did not change on awakening because they had remained high all night and there was a higher level of inflammation in our depressed group.”
Prof. O‘Keane said the brain was always vulnerable to being damaged but the developing brain, up until people reached their mid-twenties, was more vulnerable. As children grow up their stress systems are also being modified and if they have been exposed to adversity, sexual abuse or neglect their stress systems became “set” at a higher level. As they developed into young adulthood they may become unable to bring down their cortisol levels and their systems could become permanently damaged.
“We are looking at treating depression assertively to modify these stressors and help people become less stressed in later life.
“I would like to thank the Meath Foundation which gave me money for this body of work and led to our getting a Health Research Board grant which we have just been awarded. This would not have been achieved without the project being initially funded by the Meath Foundation,” said Prof. O’Keane.