Researchers at the University of Seville have analysed alterations in the cerebral cortex in people suffering from psychosis. Their findings show that psychosis does not follow a single trajectory, but rather its evolution depends on a complex interaction between brain development, symptoms, cognition and treatment. The authors therefore emphasise the need to adopt more personalised approaches that take individual differences into account in order to better understand the disease and optimise long-term therapeutic strategies.
Psychosis is a set of symptoms—such as hallucinations and delusions—that are common in schizophrenia and involve a loss of contact with reality. From their first manifestation, known as the first psychotic episode, these symptoms can appear and evolve in very different ways between individuals, thus making schizophrenia a particularly complex disorder.
The results of the study show that, at the time of the first episode, people with psychosis present a reduction in cortical volume, which is particularly marked in regions with a high density of serotonin and dopamine receptors, key neurotransmitters in both the pathophysiology of psychosis and the mechanism of action of antipsychotics. The data also suggest that both neurons and other brain cells involved in inflammatory and immunological processes may play an important role in the disease.
These structural differences tend to diminish during treatment, thereby suggesting that the rate of brain deterioration is attenuated by clinical intervention. However, more marked differences persist in people who receive higher doses of antipsychotic medication over time. This does not necessarily imply that the medication causes volume loss, but rather that those patients with more severe symptoms often require higher doses.
The study also confirms that these patients show cognitive impairments from very early stages. Throughout follow-up, many individuals experienced improvement in both symptoms and cognition, thus suggesting that clinical stabilisation may be accompanied by partial recovery of these functions. However, this improvement is less pronounced in those who require higher-dose treatments.
In the study led by Claudio Alemán Morillo and Rafael Romero García at the Neuroimaging and Brain Networks Laboratory of the University of Seville, and published in the British Journal of Psychiatry , magnetic resonance images were acquired to calculate the volume of different regions of the cerebral cortex in 357 patients with schizophrenia and 195 controls.
One of the most relevant aspects of the study is that the participants were evaluated over a period of ten years, thereby allowing an analysis of how the brain changes in the long term and how these changes are related to clinical symptoms and cognitive performance, including possible difficulties in attention, memory, or processing speed. In addition, the study applies a percentile-based analysis for the first time. Just as percentiles are used in paediatrics to identify deviations in weight or height, they can now be used to detect whether certain brain regions have atypical volumes.
The British Journal of Psychiatry
Medication and atypical brain maturation in psychosis associated with long-term cognitive decline and symptom progression
11-Dec-2025