TEDxPrague 2010 - Cyril Höschl - Vrozené vs. naučené

Good afternoon. The main question that doctor hears the most often when parents bring an insane child is: doctor, please, where did it come from to our family? Who did the child take after? Footnote: it must be from my husband's side. Or in a better case: who is responsible for that? Where did we make a mistake? And the answer is very difficult, but it's worth a while. . The question if when two blonde parents have a child with black hair means that the father has to be a postman was already answered by Gregor Mendel, the founder, the father of genetics, abbot of an augustinian monastery in Brno in 19th century, when he cross-bred his famous peas. And this example is extremely simple and I think that everybody will understand. If you imagine that a quality, a gene for the quality, for example the colour of the pea petals is either red or white and so the gene has these two variations, and the red is so called dominant, which means that it's enough if you "buy" it either from dad or mum and you will have red petals. Whereas white is so called recessive, it won't be evident unless you buy it from both mum and dad. So when the problem is set like this and this is how it works in nature, then everybody in the next generation has red petals. But when these two red have children afterwards, there's probability 1 : 3 that those two recessive genes will meet there and so from time to time, a blonde child appears or white petals. This is called a genealogical tree, this is how genetics started and began to study relation between different features, even character, mental disorders and a possible genetical burden by watching how does the disorder appear in different groups, for example in families. And it was claimed that the more people are related the more shared genes they should have if it's genetical and there should be a bigger probability, that there will appear something that is set by these genes. This way, they found out for example, that when you are an identical twin and your sibling has schizophrenia, the probability that you will have it as well is almost 50%. If you are fraternal twins, the probability is only 17%. And so on. When you are only an uncle and a nephew or niece down to general non-related population, which is from half to 1 per cent. This dramatical increase leads everybody immediately to the conclusion: yes, schizophrenia is genetically given disorder, because the more related we are the bigger risk we have. But that is only a half of the message. The other half of the message is that more than a half of the identical twins doesn't have schizophrenia and yet they have 100% of the same genes. How is that possible? If it was genetically given, they would always have to have it, because they have all the genes identical. But they don't. So both is truth. The problem of these genealogical studies is that there is the danger of wrong interpretation. When you look at the 60s in Germany and you compare the increase of number of nesting storks with the increasing birth rate, as a scientist, you can make a conclusion that children are brought by a stork. This is how science works. Because some saw through, they started assessing not the population risk, but molecular biology and progress in genetics and they were allowed to observe with lab methods the genetical risk and specific genes, that we look at and study whether the schizophrenia patients have them or not. The signal that we get this way is there, but it is very weak, and it was a huge disappointment, considering the millions it cost and the effort and grants and I don't know what else... Moreover, and this is from our institute, the identical twins, these are two brains of identical twins, siblings that have 100% of the genes same even have different hardware. You can notice that the left one has much bigger chambers, that's the black thing, and these are spaces between brain gyri, and conversely has less of brain matter, that's the light thing, than the right one. NAAS, that's n-acetyl aspartate, is a substance that my colleagues examined by magnetic resonance spectroscopy, and this substance is directly responsible for neurone density and their power. And it is a slight difference, but statistically it's bigger in the right one. And one twin had schizophrenia, and the other didn't have schizophrenia. And they have the same genes. So now what? It seems, and this is pointed out by Rudolf Uher, an ingenious Czech who works at King's College in London, that genes don't cause disease as Mendel thought about the peas, that there was a gene that produced red petals, so here would be a gene that would produce schizophrenia. Or that there is some environment, psychoanalysts would claim that childhood traumas, or infectologists that viruses or so, teachers that bad upbringing, and so on. That environment influence leads to some disease. The reality, and that is becoming clear and is the reason why it's worth speaking about it, is that environment influences the way in which the genes apply, how they express. And conversely, the genes influence the sensitivity to the environment impacts. So all of this is true, but it's more complicated than everyone originally thought. It was nicely studied by Michael Meaney, a psychiatrist at McGill University in Montreal, who says: imagine that you have one gene, one and the same gene, here marked as X, which during an individual's childhood gets to environment A. Environment A causes the gene to express, which means it replicates, it is active, and leads to creation of protein, and there is plenty of it. Conversely, in environment B, which acts differently, it is not active, does not replicate, and as a result, these two individuals are completely different, although they have the same gene. Now this is about the identical twins. Because the way how the gene works is influenced by the environment. Michael Meaney studied this by brilliant experiments, he observed laboratory rodents, you can imagine rats, and their maternity behaviour. Maternity behaviour among rodents is licking. Rats, hamsters, and so on, when they have babies, they lick them. In English slang, it's even said licking and grooming, they also lick fur, and it's shortened LG, so when you're on date, you can LG. Licking and grooming. And he found out, when he was just observing mothers, that some lick quite little, others lick much. And, of course, the most of them licks just accurately. But those that lick accurately were of no interest for him, he observed only those that licked very little and those that licked much. And he found out that children of those that licked little have too many stress hormones, while they have less of them. On the other hand, the gene for glucocorticoid receptor, the one that provides feedback when you're under stress and can switch off stress axis, expressed only slightly, although it should be there. Also the ability to suppress the stress axis is much better among the heavily licked. Even more, the fear is much bigger among the lightly licked than those heavily, and conversely curiosity, exploratory activities, intelligence, the ability to find a way in a maze is much better than among the heavily licked, nota bene it is measured by so called novelty suppressed feeding, which is an experiment that makes use of rodents' fear of light and open space, so they are starved out and food is then put to an open, lit space, and you measure time how long it takes until they gather courage to fetch the food. If you give them diazepam, they go earlier. What's interesting about it? It's interesting that the pattern of those lightly licked, that means stress, fear, unconcern and worse performance in maze, or among the heavily licked resistance, courage, curiosity, better performance in maze, is the same among mothers and their children, and when these children become mothers, then among them and their children... We inherit genes, so is there a gene for licking children and also be brave and intelligent? Or is the bravery and intelligent only because they were licked so during childhood? Now comes the punch line and Michael Meaney's genius, which is always in the absolutely easy experiments, and we all are angry that something so evident was discovered by this Canadian and not by us. It is an adaptive study, in which he switched them, so no mother had her child, so there were children heavily licked from heavily licking mother, heavily licked from lightly licking mother, lightly licked from heavily licking and lightly licked from lightly licking. Then he looked at the behavioural patterns they had, and he found out that they were according to how their mother licked them, not which genes they inherited. And this is a greatly important discovery in nature and nurture. They even demonstrated how this happens. It is a way from caress, through serotonin 5-HT7 receptor, protein kinase to nerve growth factor that pulls in various enzymes, histone acetyltransferase, demethylase, I won't bother you with that, which demethylate and acethylate genetic code, and the acethylated genome works better and better produces receptors for stress hormones and pre-programmes the person to be resistant against stress. And the mothers, through licking them from the first moment, switch their children's genes for the whole life. Then it is decided what would become of them and what they can resist. Now, let's get back to human world, we're almost at the end. Let's take e.g. depression, which we all imagine as hopelessness, we don't want to live anymore, we'd better end our lives. This is studied in three domains: One is activation of stress axis -- we've already discussed that. Second is depletion of monoamines -- that is psychopharmacological domain -- a the third is psychological -- these are depressive cognitive schemes which all inter-relate and create bad temper, biologically and psychologically. If you want to hear what depressogenic cognitive schemas are, a nice example is given by Paul Salkowski, one of the founders of cognitive behavioural therapy: In the morning, on your way to work, you step into a dog poop. If you're controlled by depressogenic cognitive schemas, you say: "That's exactly me, this could only happen to me, the whole day's gonna be like that, that's my whole life, I wish I'd never been born!" If you're controlled by anxious cognitive schemas, you say: "Now I'll have to go back to clean it up, in the meanwhile, the bus runs away, I'll come late to work, he'd say I have attendance problems; if I don't go back, he'd say I have a problem with hygiene, oh, he's about to fire me anyway." You speculate, don't sleep at night, etc. If you're controlled by paranoid cognitive schemas, you say: "Of course, that was the neighbour's dog, call the police, put him to the court." And then there is the fourth option, that's the psychotherapist, he says: "Isn't it a lovely day today that I haven't forgotten to wear shoes?" If you prescribe antidepressants, you're cutting heads off this multi-headed dragon on a biological level, if you treat by cognitive behavioural psychotherapy, you cut them off elsewhere, anyway, you decrease the depression, all this based on a genetic vulnerability that was proven by Caspi in Science several years ago, and it can be nicely seen on a relationship between neuroticism, which is a genetic feature, and depression's progress under some stress. This horizontal axis shows how much stressed you are, that's from Kettler's work from 2000 American Journal of Psychiatry, where you can see that the bigger life pressure, traumas, strokes of fate, the bigger probability, risk of developing depression. However, it also matters how neurotic you are in term of neuroticism measured by tests. And it even seems, especially among women, that being neurotic means having equal or higher risk of developing depression than woman that is heavily tested, but not as neurotic. So, there is, it seems, something like a dual quantifier. Result: Not genes, not life events, can explain reasons of main psychological disorders, but when put together, they fit like LEGO bricks, and it starts to give a meaningful signal. That's the message I wanted to say. So, genetic set plus some infection, mother's viruses during pregnancy, toxoplasmosis, plus smoking weed in puberty, plus some factor that we maybe don't know, equals schizophrenia. The same plus stress, strokes of fate, deaths of relatives, equals depression. Or: genes and bad social learning equals anxiety. Or: genetic set and environment, such as whisky stillroom near in Baikal area, increase chance of developing alcoholism. It seems it holds that either you're quite immune, and then there have to be big strokes of fate, or you're very vulnerable, and then nothing has to happen to give the same result. Let's finish with a paraphrase that relationship between genes and behaviour is similar to one between body height and ability to play basketball. You can be high, it gives you advantage, but if you're an oaf, have five dioptres and can't even hit the garbage bin, it won't help you much. On the other hand, you can be smaller, quicker, have good shot and run fast -- so this is how it is with our genetic set and our ability to achieve something in life. Thank you.