Argyris Stringaris, MD, PhD, FRCPsych, is a Professor and Senior Investigator at NIMH who researches and treats depression and related conditions in young people. He is a Professor of Clinical Psychiatry at Georgetown University.
Professor Stringaris is an expert in depression, in his open-minded and pragmatic approach, he doesn’t have an ideal term for depression but feels that patients deserve more clarity in their diagnosis and prognosis. He leaves psychiatrists thinking about the complexity of the disorder and asks us to be more open-minded in research, training and clinical practice. Here, he explains a little about what the current term is not giving us, or what it is.
He continued to talk on the matter with our editor.
Is therapy being correctly administered in this umbrella term of depression?
“In the absence of clear alternatives, we need to continue with what we have. We must be aware of the large heterogeneity involved in depression. If you diagnose me with depression, which is the first episode of depression for me, it is very hard initially to know if this will be a single episode of depression or a series of recurring problems. About 50% of persons who have a first episode of depression, only have this single depressive episode. Therefore, imagine the implications this has on how aggressively you should treat someone in these initial stages. Apparently, the rate of spontaneous remission is higher in young people. This gives you a sense of the difficulty we are facing in treating depression, specifically in young people. Basically, we need to ask what does the diagnosis means for prognosis and for choice of treatment? We need to clearly improve this and we need to invest a lot of effort in improving this. This may involve breaking down depression into subgroups or thinking of other ways of doing so, at the moment, there are not some fantastical alternatives”.
Where are we with using biomarkers to complement the self-report in the diagnosis of depression?
“Fundamentally, in medicine, the human report of human suffering is at the epicenter of the evaluation. There’s not much point in having a biomarker without this self-report. It must correspond somehow to what the person tells us about how they feel. The self-report is, thus, fundamental. A biomarker is helpful in those cases where it can tell us something about the future of this patient, which the current self-report cannot tell us. The current self-report is very cheap to implement and is useful, but can we develop a blood test, or can we scan a brain that can tell us something relevant for this individuals future and prognosis. This is the key. These types of biomarkers do not yet exist. There are many studies on neuroimaging and other techniques that are trying to capture predictions of the future of some patients. We are quite good at a group level, what we haven’t yet managed to do is to use markers to predict on the individual level. For this to happen, we need different designs with relatively large samples, which is increasingly happening, and new techniques in prediction, for example, taking lessons from machine learning and computational psychiatry, and we need to be very rigorous about it. This is going to take considerable time to achieve”.
Understanding the reward system in depression
“There is an approach to depression that sees a pathology of rewarded sensitivity. There is some merit to it, a key symptom in depression is anhedonia, basically a lack of interest in things that use to be pleasurable or an inability to derive pleasure from things that use to be. People have extrapolated from that by trying to find the area in the brain that underlies this kind of abnormality. Of course, not all patients diagnosed with depression experience anhedonia as a leading symptom. But anhedonia as a symptom is a predictor of worse outcome after treatment and prognosis in general. It is an important symptom, but it is very rare to find a depressed patient who is unable to drive any pleasure. One of the fascinating things in depression is that we have comorbid additional problems that indicate an excessive reward seeking behaviour, for example, those who eat excessively, or drink a lot of alcohol or take drugs, or those who have pathological gaming behaviour. The comorbidity of depression tells us that it’s not just about a part of the brain missing or a lesion to therefore have this pathology of reward, it’s more than that, there is something else going on, specifically, a reward dysregulation. We don’t know what this means, or how this is happening. What we do know, more and more through our computational psychiatry models is that the way we report our feelings is very much dependent on the history of rewards in our environments. But there is the issue of different rewards for different people, what may be rewarding for one person may not be rewarding for another person, and this is something we need to grapple with in this field. It is a very promising field, but again we need to be careful as what we define as reward, what we define as punisher for example”. He goes on to explain how stressful early life events can also influence the reward system. “Others, and our group, have shown that the reward system is impacted upon by early life events. At least the two are longitudinally associated. What we see is that individuals with early life difficulties, on average, are more likely to show aberrations in the reward system. It probably rewires the reward system in ways in which we are yet to fully understand. We do have evidence from the animal literature to support this, but more is needed to fully understand it”.
What is the future of mood disorders?
“What is necessary is that we need big investments from governments and other organisations to tackle the knowledge gaps in mood disorders. The investment in metal health is generally very low compared to other medical disciplines. But investment alone will not do the trick. We need to, as a discipline, embrace complexity. We shouldn’t throw out all the evidence gathered over the history of depression, but clearly something else needs to happen. We need to embrace the complexity by learning from other disciplines, in particular, computational disciplines such as mathematics, statistics, machine learning, and data science; these are extremely important to incorporate into our research efforts. I would also argue that these aspects should be incorporated into the training of young psychiatrists, so they understand the language of these disciplines and learn from them, incorporating them into the future of psychiatry. On the other hand, we need to be bottom-up and very open-minded by listening and learning from the patient. Rather than having our own sealed categories, we need to go back and build our concepts from the bottom up, which will help us and make the outcomes in our trials, the measurements we do, more meaningful for people, and that’s ultimately why we do all this. The patients need to have a say. This is a difficult process, and it will take some years, but the expansion in these directions will be extremely important”.
Professor Argyris Stringaris will give his keynote presentation at 11h00 CET on Friday 25th June 2021 online at the ESCAP Expert Day. Register now.
