Principal Investigator Prof. Veronica O’Keane
Research Title: “Mapping the experience of Depression in the Brain and Body.”
Meath Foundation research funding awarded 2019
A research project which she and colleagues carried out in Dublin, has shown that depression is a disease, Prof. Veronica O’Keane, Professor in Psychiatry at Trinity College, Dublin and Consultant Psychiatrist at Tallaght University Hospital and the HSE, told the symposium.
She said their research had shown the clinically depressed group had higher cortisol levels, their right amygdala, which mediates negative emotions, was enlarged and the size of their hippocampus (or memory centre) was reduced.
Their study had also shown that the size of the amygdale was related to the cortisol levels.
Prof. O’Keane, was speaking on “Mapping the experience of depression in the brain and body.”
The researchers worked in Tallaght University Hospital, the HSE and the Trinity College Institute for Neurosciences. The work was carried out in the TCD Institute and published in Biological Psychiatry.
Using neuroimaging, the study looked at the emotional, somatic and cognitive feeling people experienced when depressed, how these experiences mapped on to the body in the shape of stress systems and how they mapped on to the brain in terms of brain centres for stress, emotion and memory.
“The amygdala is the integrative centre for emotions, emotional behavior, and motivation in the brain and the novel finding from our studies that the size of the amygdala was related to the cortisol levels, was very interesting. The more stressed or depressed people are, the more likely they are to have negative emotions. So, we measured their cortisol levels and they were higher in the depressed group. We also found that the memory centre, the hippocampus, was shrunken in people with depression.
“So, overall, there were two messages from the studies. The first was that the size of the emotional centre, that mediates bad and negative emotions was increased in depression, which correlates with stress levels. And the second finding was that the hippocampus, the memory centre, the cognition centre, was reduced in size in people with depression.
“We also found that the more severe the depression was and the longer the person was depressed, the more shrunken the hippocampus became. Clinically that’s very important, because we should be encouraging our patients to seek active treatment for depression.
“When our research appeared in Biological Psychiatry, a very high impact journal, they also devoted the editorial to our work. I think that was because the editors liked the idea that we were finally saying that depression is a disease, not just something that happens and goes away. If it is there for a long period of time, it can damage your memory. So, it is important to treat depression.
“I think a lot of studies in depression and in psychiatry in general, look at symptoms, and sometimes the reality of those symptoms doesn’t necessarily strike home to us. If somebody has a pain in their abdomen, everybody can identify with that. But I think that maybe with depression, we don’t focus sufficiently on what the patient is actually experiencing.”
I think this goes back to Freud, who, as you know, was a neuro-psychiatrist. People stopped looking at the brain at that point and since then, there has been a tendency to look at psychiatric illnesses as if they all had a developmental origin. The psychiatry journey in America and Britain was highly influenced by Freud and they went in a very psychoanalytical direction.
“When I was a young person, it would be a very strange thing to be known as a biological psychiatrist. That was really prior to neuroimaging techniques which have enabled us to visualize the brain.
Prof. O’Keane said the experiences in depression fell loosely into three categories – emotional, somatic and cognitive – and you could separate out patients in terms of these functions.
She then discussed how the experience of depression mapped onto the body and in many ways the experiences of depression were those of extreme stress.
“Memory is really what is disrupted in depression. Now, if your memory is disrupted or impaired in any way, your ability to learn, and your ability to function even at the level of a conversation, would be impaired. If you are having a conversation and are having problems with your short-term memory, you may forget what you are talking about by the time the conversation ends.”
She said the hypothalamus was the exit point for all the influences that were going into the brain, the sensory influences, memories, the current life stressors with which people were trying to cope. The hypothalamus also controlled the cortisol release in the body.
People had an increase in cortisol in the morning when they woke up to enable them to get up, look after the kids and go to work or whatever. So, the cortisol level was high in the mornings and then hopefully tapered off in the evenings, enabling people to sleep.
“However, if you’re depressed, your cortisol levels do not go down. They are higher in the morning and that’s why you wake earlier, and they stay higher during the day. So, depressed people are significantly different to healthy people at this point because when the rest of us are struggling to wake up, they’ve been awake for hours.
“We decided the best way to measure whether a person had the hormone profile of a depressed person was to look at the stress hormones that were present when they woke up in the morning.
“We think about emotions as being something separate to stress, but what creates the emotions in our body is the same system that creates the hormones. But instead of going out through hormones, it goes out through our nervous system and that enervates the heart, which is why when people feel stressed, or when they feel sad, they may lose their appetite, have butterflies in their stomach, have a pounding heart.
“However, it’s important to say that some emotions are non-specific – people could have a pounding heart because they were happy, or excited, or because they were really fearful.”
Prof. O’Keane said if somebody was actually severely depressed, they were more likely to respond to treatment. If they were resistant to anti-depressants they probably were not actually clinically depressed.
“I would say, now, within the cohort of highly resistant, sick, depressed patients, we’re like every other discipline. You know, we have some patients where treatment is palliative and some patients who are in hospital the whole time, but the vast majority of patients are treatable.
“I would say again, people don’t really understand that the treatments that are there for depression are hugely effective. We have done a five years study with Thomas Frodo, who was doing similar work. He looked at people five years following their initial presentation and all but one patient out of 30 had got better, or significantly better. They weren’t all in remission, but they were doing well.”
Prof. O’Keane said she was deeply grateful for the body of work that the Meath Foundation had very generously funded. “It enabled me to do the foundation work that led me to get other grants. At this point, we’ve completed four PhDs, three Laidlaw scholarships and we’ve published 15 papers on this area. This work presented today is funded by the HRB and by the Meath Foundation, and without the Foundation, I don’t think this work would have got to the point it is at now.”
She also wanted to thank the REDEEM team, which had worked with her on the study. They were Chloe Farrell, Chai Jairajm Leonardo Tozzi, Niamh O’Leary, Erik O’Hanlon, Darren Roddy, Amy Adair, Clara Mai Fitzsimon, Andrew Harkin, Tomas Frodl and Martina Hughes.