Psychology and Neuroscience of Affective Disorders PDF

Module: Psychology and Neuroscience of Affective Disorders Week 3: Biological alterations of affective disorders Topic 1: The role of the gut microbiota in affective disorders (Part 2 of 4) Lecture transcript Viktoriya Nikolova, PhD student Department: Centre for Affective Disorders, Academic Psychia...

Module: Psychology and Neuroscience of Affective Disorders Week 3: Biological alterations of affective disorders Topic 1: The role of the gut microbiota in affective disorders (Part 2 of 4) Lecture transcript Viktoriya Nikolova, PhD student Department: Centre for Affective Disorders, Academic Psychiatry Slide 4 In this part we're going to look at the differences in the composition of the gut microbiota between people with and without affective disorders. This comes from observational studies in which we take two samples from a group of patients, and compare that to demographically matched healthy controls. This comparison is done using sequencing methodologies, most commonly 16s rRNA sequencing. So what this does is that it sequences. It analyses the rRNA gene, that is present in almost all bacterial species. So by targeting particular regions of the gene, we can target specific bacterial populations that we know are present in the human gut. And when we talk about composition of the gut microbiota, we generally mean two things. Its overall diversity, that is, how many different species are there, and the abundance of individual microbes. That is, how much of each species is there. Slide 5 Generally speaking, the more diverse the microbiota is, the more beneficial for health. But what does that mean? Have a look at this figure Panel A, which comes from the recommended reading list. What this shows is the two main factors in calculating diversity, © King’s College London 1 richness, and evenness. So if we only look at the top half, richness, what we see is that the more rich in species, the more numerous species there are, the more diverse the environment is, and therefore the better. However, if we're only looking at richness we might not get the full picture. For example, if we said there's a student at King's College, London, from every single nationality in the world, we may think this is amazingly diverse. However, if we also account for evenness, which means how evenly are these different nationalities represented within the community, we will see perhaps a different picture, one that is less diverse, which would be natural. So this is the case in the gut as well. We don't want only higher richness of different bacteria, we also want higher evenness, so that it's not dominated by any single species that may be either good or bad. Once we have measured these factors, we can then compare the diversity of the microbiota between groups, that is between patients with affective disorders and healthy controls, for example. And this is shown below in Panel B. And what we would expect to see is that in patients with any condition really, diversity is significantly reduced compared to healthy controls. And what we also expect to see that's shown on the bottom right panel is that symptom severity is negatively correlated with diversity. So the lower your diversity, the worse your symptoms are. And for example, in patients with gastrointestinal conditions where the gut is the primary location of disease, this is very much the case, and it's very clear to see. Slide 6 And the other thing that we compare in terms of good composition is bacterial abundance, that is, is the microbiota of people with anxiety, for example, containing higher or lower levels of some bacteria compared to healthy people? This figure is from the same paper, and it shows the results from this type of analysis. So as you can see, some bacteria decrease or increase in depression, these are the blue arrows. And some are decreased or increased in anxiety, those are the red arrows. The picture is showing the bacteria according to their taxonomic rank from phylum, all the way down to genus. And below genus is only species which is not shown in this graph. Slide 7 So what is happening in affective disorders specifically. So several small studies have found altered microbial composition in patients with depression, and what it means in terms of diversity. They have found decreased diversity and specifically this was found for richness of species. These studies have also found a reduction in levels of bacteria such as bifidobacterium and faecalibacterium. Bifidobacterium is one that you may have heard about because it's a common ingredient in many probiotics and supplements that are available on the market. And generally has health related properties and benefits. And faecalibacterium is a very prevalent good microorganism that has anti-inflammatory properties, and it also is involved in the production of short chain fatty acids, specifically butyrate. What these studies have also found is increased diversity in specifically pro inflammatory bacteria, and that the levels of these bacteria are also increased in patients with depression. Slide 8 And what about bipolar disorder? Here we can see the results of a recent systematic review examining 13 case control studies of gut microbiota composition in bipolar disorder and 2 © King’s College London healthy controls. They in fact found very similar things to what I showed you in the previous slide about depression. They found decreased diversity in bipolar disorder compared to healthy controls, and similarly reduced levels of anti inflammatory bacteria and increased levels of pro inflammatory bacteria. Slide 9 Now let's take a step back and look at the bigger picture. Let's look at depression, for example, in the wider context of psychiatric conditions. Are the abnormalities that we see in depression and the ones that we saw in bipolar disorder unique to these conditions? And also another step back we need to take is from individual studies just like the ones in the previous slides, that are small scale studies, and look at the wider literature. And why is that important to do? Because small sample studies can sometimes produce inflated and non-representative results. So, for example, many of these studies come from populations in East Asia. And then, when some come from, for example, America, there can be big differences in population characteristics. So as I mentioned in the first part of this lecture, many factors can impact the microbiome, including geographical location, diet, lifestyle habits, which can vary a lot between East Asian populations and, for example, American populations. Slide 10 So this is a paper that we published in JAMA Psychiatry in 2021. And what we did is we summarised all case control studies that were available at the time throughout the spectrum of psychiatric disorders. So these were 59 studies, and we performed a meta analysis of all the diversity findings. So we put all of these together, and what we actually found was there were no significant differences in overall diversity, which is not really in line with what I mentioned earlier about the decreased diversity in these conditions. The only exception was, in fact, bipolar disorder, where the findings on diversity, even though from fewer studies, remained consistent. So this really does show you that it's important to look at studies as a whole, rather than just focus on small scale studies. And in terms of microbial abundance, we looked at this according to disorder subtype. And what we found is that, the differences between patients and healthy controls are not really distinct according to disorder subtype. So we saw a transdiagnostic pattern between depression, bipolar disorder, schizophrenia, and anxiety. So this corroborates the findings that I mentioned in previous slides that some anti inflammatory butyrate reproducing bacteria were depleted, and some pro inflammatory bacteria were enriched. Slide 11 Perhaps it's useful for you to think about, why is it that we're not seeing disorder specific patterns? Is it because there's a big biological or perhaps even genetic overlap between these conditions, or are there other shared features? Like for example, depression is a feature of several of these conditions. It's in fact, part of the diagnostic criteria for bipolar disorder and schizophrenia. And it can also be highly co-morbid with pretty much every mental health condition. 3 © King’s College London