It is a concern that is especially known to everyone who has had to enter a psychiatric consultation. Will the day come when mental disorders are measured, partially or completely, with objective parameters? Will psychiatrists stop interpreting subjectively, improvising and operating through trial and error? They are not simple questions; nor wastelands. These are questions that, although timid and late, are managing to emerge from their traditional ivory towers: laboratories, universities and research circles. But will they ever be able to reach mental health clinics? To take a look at the psychiatry of the future, it is necessary to talk about personalized medicine and precision psychiatry.
Personalized medicine is a medical approach that aims to incorporate as many individual parameters or variables as possible into diagnoses and treatments. That is, going from a generic treatment for anyone who has a specific symptom or disease to one adapted to the person. It is not something new; has always tended towards this model. Hippocrates, in the 5th century BC, already worked like this, sensing what proportion of blood, phlegm, yellow bile or black bile was altered in each patient. Claude Bernard, in the 19th century, stated: “A doctor is not a doctor for living beings, not even for humanity, but a doctor for the person; and even more, a doctor for an individual in certain particular morbid conditions, in his idiosyncrasy.”
The incorporation of fully objective variables to this personalization intention is more recent. A good example of this is the framingham study, a research project that began in the city of the same name in the State of Massachusetts, United States, in 1948, and that has not yet concluded! Thanks to their results, cardiologists are able to stratify their patients into different cardiovascular risk groups, and thus predict the probability of events such as a myocardial infarction. To do this, they take into account clinical variables (such as blood pressure), environmental variables (such as smoking) and biochemical variables (such as cholesterol). Currently, in areas such as oncology, knowing the genetic lineage of the cancer in question is much more decisive for treatment than describing its symptoms or even its exact location. The definition of these groups based on particular biology, defined beyond external symptoms or phenotypes (from the Greek phanein“appear”, “show”), allows us to know what happens to each person and choose the best treatment for them.
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And what role does psychiatry have in all this? Mental disorders and objective measurements. Psychiatry and analytics. Aren’t these great oxymoron couples? Indeed, the couch has traditionally been associated with that which is subjective. Starting with psychoanalysis: what does this dream, or this symptom, mean to you? Or, entering any query today, how is your mood? This approach is not necessarily bad, nor is it necessarily good. That’s it: subjective, and also very current.
On the other hand, in our collective imagination, the laboratory embodies all those parameters labeled as objectives: grams of glucose per deciliter of blood; millimoles of sodium per liter of blood. All of them immutable, measured with undeniable precision, reliability and validity. Something typical of so many other medical specialties.
This is where we come in with precision psychiatry. This term, coined for the first time in 2015 by Dr. Eduard Vieta, stands as the reflection of this personalized medicine, applied to the study of mental disorders. There are various variables that have come to the fore with a clear message: “I am the one who will let you know what is happening to the patient”; “I’m going to tell you how to treat him.” But many times we cannot trust them. Most have been rejected outright, others have been left aside, and some are still there, trying to persuade us. I am thinking, for example, of genetic analysis techniques, such as cytochrome P450 genotyping, which have been established with more or less success and are currently used to predict the tolerability of certain drugs. I am also referring to polygenic risk scores, in which the influence of hundreds of different mutations on the development of a certain mental disorder is studied. And, in a more mundane way, I also think about all the data that will soon be collected through our smartphone: quantity and quality of sleep, daytime activity pattern, among others.
One way or another, no one is aware that these immense, almost infinite sets of data will require new and more powerful statistical analysis tools. Indeed, it seems the time for artificial intelligence and the newly arrived computational psychiatry; tools that, from their black boxhelp us interpret what the human mind seems to lack sufficient algorithmic power for.
Now that we have reached the year 2023, scientific progress seems to have reached levels that were unimaginable until recently. One of the most promising lines of research are extracellular vesicles (ECVs), microscopic fat droplets that are continuously released from all the cells in our body and contain molecular information (proteins, nucleic acids and lipids) from their place of origin. The important point, our narrative turn, is that in recent years we have learned to isolate from the blood those that come from the brain, make them “explode” and analyze their content. This, in turn, provides us with live information about what is specifically happening in our neurons: are they inflamed? Is there an alteration in their glucose uptake? Is it rather a problem in the function of their mitochondria, or of any other of its components? The vesicles function as a kind of liquid biopsy, providing us with data directly from our king organ. And the thing is that, until now, many of the parameters that we measured in blood were general, systemic, and could be telling us about problems that had their origin in other places; perhaps in the kidney, perhaps in the liver, but always sowing some confusion. VECs modify the landscape of variables that we can capture and use; a turn that is not only more precise in the quantitative field, but also different qualitatively.
In short, this new way of measuring, terribly more specific and, therefore, more scientifically valid, will greatly facilitate the transition from psychiatric phenotypes (patterns of thoughts, emotions and behaviors, as when we say “major depressive disorder”) to endophenotypes either biotypes (our biological characteristics). Thus, through the endophenotyping of patients with mental disorders (especially severe ones), we will be able to stratify them into biological boxes and it will be easier (and more consistent) to limit pharmacological treatment. A blood test may be decisive in determining the right psychiatric medication. A change that, in queries, could take the following format:
Reason for consultation: “Doctor, I feel so bad that I am unable to leave the house, and we have already tried five drugs.”
The doctor, currently: “I understand, let’s change the drug” (the next to the corresponding clinical guide, prepared according to clinical trials designed according to the phenotypes).
The doctor, in a few years: “I understand, let’s ask for an analysis, let’s analyze your endophenotype and let’s choose the treatment based on the results.”
Imminent revolution? Don’t know. But it is evident that there is a new player in the personalized medicine card game: precision psychiatry. And, although young and inexperienced, he has, perhaps, the best hand. Take a seat and hold on; the show is going to start.
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