"Understanding the genes involved in OCD opens the door to precision therapies"

This is a study carried out by the International Consortium for Psychiatric Genomics, of which the Bellvitge University Hospital is a part, which collects for the first time a sufficiently large sample of people with OCD to be able to study in depth the genetic factors involved in this disorder .

We knew, as a starting point, that it is a polygenic inherited disorder, meaning that many genes are involved and each one contributes a small increase in risk. However, this study confirms that the genes most implicated in the risk of developing OCD are not randomly distributed throughout the human genome. We have been able to detect up to 25 genes specifically associated with the risk of developing this disorder, concentrated in approximately 30 loci, or chromosomal regions. These genes are particularly expressed in certain neurons and brain areas related to decision-making, memory, and higher-order cognitive functions.

This work confirms that OCD is a disorder involving hundreds or thousands of genes that are expressed in complex brain circuits, whose interaction contributes to its development, and it has been possible to identify in which regions of the chromosomes the greatest genetic risk is concentrated.

Approximately 40% of the risk of developing obsessive-compulsive disorder (OCD) has a genetic basis, but until now we were completely unable to identify which genes were involved. This study has finally allowed us to detect the genes implicated in the development of OCD and understand their impact on brain connectivity circuits. This opens up the possibility of significantly improving prognosis and treatments through precision medicine, similar to the advances made in the field of oncology.

We have been able to detect up to 25 genes especially associated with the risk of having this disorder, concentrated in approximately 30 chromosomal regions.

On the one hand, we can begin to design drugs. If I know, for example, that some of the genes associated with the risk of developing OCD are related to the synthesis of certain proteins in a specific area of ​​the brain, I can try to find a drug that stimulates the synthesis of those proteins. In other words, for the first time, we will be able to design drugs by understanding the root of the problem. And then, in psychiatry, a very interesting field is now opening up: neuromodulation . If we can detect the altered genes and study which brain regions they are most prevalent in, we can determine which brain regions might be beneficial to stimulate with these types of therapies.

There are many different factors. We know that hormonal changes , especially estrogen levels in women, can act as factors that promote the onset of OCD or worsen symptoms: the year before or after the first period, during the menstrual cycle, during pregnancy, and especially during the postpartum period. On the other hand, we know that some infections caused by different germs and bacteria can also promote the onset or worsening of obsessive symptoms, leading to neuropsychiatric conditions called PANS (pediatric autoimmune neuropsychiatric syndrome).

And then, in general, some situations that have to do with changes in the level of responsibility (starting a new job, becoming independent, starting to live with a partner…) can influence the appearance of the disorder; or also traumatic childhood situations , such as sexual abuse, mistreatment, abandonment or harassment.

A significant finding is that over 40% of people are able to associate the onset of their obsessive-compulsive disorder with some kind of trigger. This doesn't necessarily mean a direct cause-and-effect relationship, but these factors can explain why it starts at that time and not another, or why it manifests with certain symptoms and not others.

This is an achievement of the advocacy groups for individuals and families who have been very persistent in highlighting and advocating for this need, alongside professionals. Of all mental disorders, obsessive-compulsive disorder (OCD) is probably one of those with the longest delays between the onset of symptoms and when a person seeks help , receives a diagnosis, and begins treatment. In adults, the average is between seven and ten years, and in children it is somewhat shorter, but it depends on whether parents can detect the symptoms. This delay has several explanations: some people are unaware that this is a disorder, believing they are simply quirks or idiosyncrasies; others, despite understanding that what they are experiencing is not normal, are unaware that it is treatable and that they could receive help; and some people do not seek help out of shame.

It is important that clinicians have experience and training in OCD to recognize less common obsessive symptoms such as fears of contagion and rituals involving washing and disinfecting. It is also important that they not be alarmed if the person talks about aggressive or sexual obsessions, and that they understand that these are very common symptoms of obsessive-compulsive disorder. And the earlier the detection, the sooner we can offer treatment and improve the person's prognosis.

Although there aren't many studies on the subject, early diagnosis and intervention , as with any mental disorder, are crucial. Keep in mind that we're talking about the onset of OCD—childhood, adolescence, early adulthood—when the brain is still very permeable, very malleable. It's a brain still with a great capacity for change and adaptation. If I intervene early, the chances of a positive response are much higher than if I let it persist in my brain for ten, fifteen, or twenty years. Simply put, regarding behavioral therapy , if I've been performing a ritual for many years, for my brain that's almost a habit. We all know how difficult it is to change habits, so imagine how much harder it is when they also have an obsessive component.

We demand that all centers in Spain have programs to address the first episodes of obsessive-compulsive disorder. If I can treat someone within the first two years, the likelihood of improvement is much higher.

It is crucial to make a correct and early diagnosis and offer effective treatment as soon as possible. This has been greatly achieved in psychosis, and it is what we are demanding for OCD: that all centers in Spain have programs for addressing the first obsessive episodes. If I can treat someone within the first two years of the onset of their obsessive symptoms, the probability of improvement is much higher.

In virtually no other mental disorder are those affected as caricatured as in obsessive-compulsive disorder. I don't think anyone laughs at people with depression, and we all know how serious eating disorders can be or what people with bipolar disorder can suffer. But OCD has been a largely ignored disorder that has barely been discussed for a long time, and cinema has primarily portrayed it through caricature.

Obsessive-compulsive disorder (OCD) can be extraordinarily debilitating and disabling . People with OCD have perfectly preserved reasoning and judgment abilities, but there is one specific area where they completely lose control. They may think they are catching a disease, that they are responsible for making a mistake with terrible consequences, that they might sexually or physically assault a loved one, that something bad will happen if they don't touch, repeat, or say something. If I have a persistent intrusive thought telling me I'm guilty of something terrible that's going to happen to me or my loved ones, any of us in that situation would do what they do: try to soothe the discomfort. This involves starting to ritualize and begin to avoid.

OCD can be extraordinarily debilitating. Some people are unable to do anything; they can't eat, they can't dress themselves, they can't leave their homes.

The most severely affected people I've seen can't even get out of bed, because just opening their eyes and deciding whether to step out with their right or left foot can trigger a brutal level of anxiety. Some people count how many times they blink, breathe, or swallow… Imagine the consequences. There are completely incapacitated individuals who can't do anything—they can't eat, they can't dress, they can't leave their homes. Although it's a very multifaceted disorder, and many people with milder symptoms will respond very well to treatment, 5 to 10% will have extremely severe forms of the disorder , and these are also highly resistant to all standard treatments . That's why it's so important that we design specific treatment programs for them.

Maria dels Àngels Giralt Ruiz

Chairwoman

Associació TOC Catalunya

"OCD is a very serious disorder, which is often trivialized"

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Over the years, we've learned that if we want to advance research into such complex disorders, it's essential that we coordinate with different centers internationally. Currently, artificial intelligence opens up a vast field for analyzing the genetic and neuroimaging data of thousands of people. If we can use machine learning techniques to analyze this data, we can detect patterns that we may not have noticed before.

In this sense, I believe that future directions lie, on the one hand, in obtaining genetic and neuroimaging data from as many people as possible and analyzing it with machine learning techniques to begin understanding how genetic and environmental factors translate into brain function. On the other hand, this will allow us to transform our approach at the therapeutic level; that is, to begin designing molecules that will repair malfunctioning areas or to start stimulating neuromodulation from the outside. I believe these are essentially the aspects we need to focus on.