It was a patient with psychosis who shaped Camilo de la Fuente’s professional career. Who would lead him to become obsessed with unraveling the link between certain brain alterations and that loss of contact with reality, to design new ways to predict the success of schizophrenia treatment, and to revolutionize its approach. It was a patient with psychosis who would lead him to become the renowned neuroscientist he is today. “I was doing a psychiatric internship, and I was fascinated. It made me ask questions, also on a philosophical level: Why does this patient hallucinate this and another hallucinate something else?” he explains.
Fueled by the desire to better understand the complex relationship between the psyche and the brain, the young man would seize a unique opportunity. At the time, the National Institute of Neurology and Neurosurgery had the first high-field MRI machine in Mexico City. “I arrived as a master’s student in the Neurology department, and they gave us the chance to use the equipment. And that’s where I sayed. It was a coincidence of life,” he recalls.
Now 53 years old, De la Fuente was just one year old when he arrived in Mexico in 1973 with his parents, Chilean exiles. “My father was a congressman in the [Salvador] Allende government; we had to flee because of the military coup. Our plane was the last one carrying refugees to leave,” he says. That flight severed diplomatic relations between Mexico and Chile, and ended his father’s scientific career overnight. He describes his father as “a very peculiar person” who studied Internal Medicine and later “conducted pioneering research in Gynecology.” De la Fuente inherited his scientific vocation and passion.
Pioneering studies
In 2000, De la Fuente began applying spectroscopy techniques to better understand the chemical processes underlying psychosis, something that had never been done before in Mexico. The results revealed neurochemical alterations that were impossible to detect clinically, providing a new understanding of the mechanisms of early psychosis, which may be an early sign of schizophrenia.
It’s estimated that of the million people living with this disorder in Mexico, about 250,000 don’t receive the necessary care — neither pharmacological nor psychiatric. And many of those who do receive treatment don’t respond to treatment.
“The vast majority of antipsychotic medications act at the dopamine receptor level. They completely or partially block a receptor for this neurotransmitter, and after a few weeks, certain symptoms improve,” he explains. “Why does a hallucination improve when a dopamine receptor is blocked?” “Nobody knows that. But the effect of antipsychotics, which have been available for 70 years, is known.”
These drugs, however, act only on certain symptoms of schizophrenia. The so-called positive symptoms, which distort reality: hallucinations, hearing voices that aren’t real, a sudden interest in religious or metaphysical themes, seeing strange and meaningless things that others don’t, delusional ideas, “this feeling of being persecuted, for example. These are the symptoms that improve,” explains De la Fuente. Then there are the negative symptoms: “isolation, lack of will to do things, and cognitive symptoms: attention and concentration problems. The medication doesn’t do much for these,” he clarifies.
To better understand the effects of antipsychotics, he decided to focus on studying what was happening in the caudate nucleus, a brain region of great importance in psychosis. This is precisely where the drugs act, blocking a dopamine receptor — a key chemical in the brain’s reward system, whose imbalance underlies various neurological and psychiatric disorders. Through pioneering imaging studies in Mexico, De la Fuente investigated its relationship with another key brain neurotransmitter: glutamate.
Previous research had linked the development of schizophrenia to alterations in the glutamatergic neurotransmission system, suggesting that dysregulation in the interaction between these two substances could explain the emergence of symptoms. “Based on this, it seemed logical to analyze, through spectroscopy studies, how glutamate was positioned at a site where medications act,” explains the neuroscientist.
A unique early intervention clinic in Mexico
Those early studies revealed that where there was a lot of dopamine, there was a lot of glutamate. “That was the first big clue,” he reveals. Following the results of that discovery, the Manuel Velasco Suárez National Institute of Neurology and Neurosurgery created the Experimental Psychiatry Laboratory, which De la Fuente now directs. There, his team develops imaging markers to guide treatment selection for first-episode psychosis.
In this outpatient emergency clinic, early care is provided to all kinds of young people with psychotic symptoms through a comprehensive approach — a service unique in Mexico. “And it’s free,” says De la Fuente. Patients undergo CT scans “that can give us clues about the existence of any structural alteration. Inflammation markers are also checked, which provide a wealth of information about an infection,” he explains.
Approximately 8% of patients who present with psychosis have a secondary cause. “It can be caused by a brain defect, an autoimmune disease, a thyroid problem… To make a good diagnosis, everything must be thoroughly examined, because the easiest way is to label it schizophrenia,” explains the expert.
Patients who come to his service also undergo an MRI to measure glutamate levels and a neuropsychological study within 24 hours. “Treatment begins that same day and is followed up. Something that isn’t done anywhere else in the country,” says the neuroscientist, proud of his contributions to clinical research on a disorder that remains so little understood.
What is known about schizophrenia is that experiences of abuse or trauma during childhood can increase the likelihood of developing it, as can living in a large city or having to migrate — possibly due to stress and discrimination. Poverty can be both a consequence and a cause in genetically predisposed individuals. If one parent has the disorder, the likelihood of it appearing in offspring rises by 17%; if both parents are affected, susceptibility in children increases to 50%. Prevalence is similar between sexes, but in men it typically appears earlier, between ages 16 and 25, and in women between 20 and 30. The reason for this is unclear, though hormonal factors have been suggested, reveals De la Fuente.
Prompt treatment after the first acute episode is crucial, as most of the neurophysiological changes related to the disorder occur at that stage. Early intervention is precisely the key to De la Fuente’s clinic, whose findings open unprecedented possibilities for personalized treatment and illuminate a path to tackle two major challenges in Mexico: “implementing primary care models in the country, and above all, this emphasis on differential diagnosis,” he points out.
The ability to provide patients with optimal treatment from the start represents a paradigm shift in effective intervention for young people experiencing psychosis. “And they don’t always have schizophrenia. A term that is incorrect,” the neuroscientist asserts.
In his view, under that label are “different conditions that medicine still cannot distinguish. There may be ten patients with the same diagnosis who are nothing alike. Some with hallucinations but cognitively intact; others with severe cognitive problems but no delusions.”
For this reason, he argues, one of the major challenges is understanding the causes of the various symptoms of psychosis. “And if we don’t understand it, we shouldn’t call it schizophrenia, but something else. We need to study the neurobiology of psychotic disorders carefully, because even among doctors, there is a large gap in knowledge. Problems that aren’t schizophrenia are often diagnosed as such, which creates even more stigma,” says De la Fuente, who last year received the prestigious Global Schizophrenia Award from the Schizophrenia International Research Society. He is the only Mexican to have won it.
An accolade that would have made his father, now deceased, very proud. “For him, it was very meaningful to see that I was dedicating myself to what his own career, cut short by exile, could not achieve,” he confesses.
A dictatorship halted one scientific career but fostered another — one that is revolutionizing our understanding of a crucial scientific field: deciphering what sets us apart from other animals and exploring the corners of the brain where our sense of self, the human mind, resides
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