"The most significant factors determining the level of functioning in patients with schizophrenia are not delusions and hallucinations. They are what are known as negative symptoms. Their core includes motivational deficit, impaired volition, passivity, emotional blunting, and impoverishment of relationships. The severity of negative symptoms determines how independently an individual with schizophrenia will function and fulfill the roles that life brings. The cause of negative symptoms lies in changes in the brain that develop before the onset of the illness itself, but the biological nature of this phenomenon is not yet fully understood," explains Filip Španiel, head of the Research Center for First-Episode Psychosis at the National Institute of Mental Health (NUDZ).

Negative Symptoms and Untreated Psychosis

Researchers from the National Institute of Mental Health (NUDZ) conducted a study called ESO, examining a group of 80 patients to identify parameters predicting the severity of negative symptoms five years after the onset of the illness. The crucial parameter revealed was the Duration of Untreated Psychosis (DUP), which denotes the time between the first symptoms of the illness and the initiation of antipsychotic treatment.

"The relationship between the duration of untreated psychosis and negative symptoms is not new, as confirmed by numerous previous studies. However, our study provided a deeper insight into this relationship thanks to detailed data. Clinically, there is a steep relationship between the length of untreated psychosis and long-term negative symptoms, particularly if it is shorter than six months. Our findings suggest that changes likely occur in the brain during untreated psychosis with a lasting impact on the patient's life, which antipsychotics can halt within a certain time frame. If the DUP exceeds 6 months, its extension no longer plays a significant role. Negative symptoms beyond this threshold are approximately equally severe, regardless of whether the DUP lasts one or two years," says Dr. Španiel.

Every Week Matters

The results were surprising even for the researchers themselves: if the DUP was shorter than six months, each additional week of untreated psychosis led to a measurable worsening of negative symptoms five years after the onset of the illness. Furthermore, with each additional week of DUP extension within this critical window, the severity of negative symptoms worsened measurably in the long term. The study indicates that the first months after the onset of the illness are critical, and early treatment during this period can prevent long-term consequences.

Schizophrenia, with its impact on individual functioning, represents one of the most severe mental illnesses. Typically manifesting in early adulthood, it leads to permanent impairment of functional capacity and disability in 60% of patients due to changes in the nervous system occurring in the first years. This disease affects more than 24 million people worldwide. The National Institute of Mental Health has established one of the world's largest research databases focused on the earliest stages of schizophrenia. The ESO study longitudinally follows and examines patients with this diagnosis from the first hospitalization. Over the first five years of the illness, researchers conduct three thorough examinations, including magnetic resonance imaging, EEG, neuropsychological assessment, various scales, and blood sampling, to understand the disease's causes. Neuroscientists at NIMH utilize advanced neuroimaging techniques and state-of-the-art laboratory methods.

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