Testing Hypotheses in Schizophrenia and Related Psychoses: From Genetic Underpinnings to Real-World Evidence

[eng] INTRODUCTION: Schizophrenia is one of the most complex and severe mental illnesses, affecting approximately 1% of the world's population. Characterized by a diversity of symptoms and a chronic course that often results in significant functional impairment, schizophrenia poses particular challenges in terms of both diagnosis and treatment. Despite multiple investigations, the precise pathophysiological mechanisms are still not fully understood, and current treatments are often suboptimal. HYPOTHESIS: 1. Individuals with a higher burden of polygenic risk score (PRS) for schizophrenia will present with more severe clinical symptoms and a greater likelihood of requiring clozapine treatment. 2. Most patients with schizophrenia in the real world would not be eligible to participate in standard randomized clinical trials (RCTs) due to common exclusion criteria, and these excluded patients will have worse outcomes over the course of their illness. 3. Long-acting injectable antipsychotics are more effective in preventing relapse in real-world settings compared to oral formulations. 4. The prevalence of neuroimaging alterations in patients with early-onset psychosis (<18 years) is higher than in community controls. 5. People with mental disorders are tested for COVID-19 less often than people without mental disorders. OBJECTIVES: 1. To examine whether PRS for schizophrenia can stratify people with schizophrenia and related psychoses based on their clinical severity. 2. To describe the characteristics of the real-world schizophrenia population that is not represented in traditional RCTs due to exclusion criteria and to compare their clinical outcomes with those of RCTs-eligible patients. 3. To compare the efficacy and effectiveness of antipsychotics for the prevention of relapse in schizophrenia, synthesizing data from RCTs and real-world evidence, with a particular focus on long-acting formulations versus their oral formulations. 4. To assess the prevalence and significance of brain magnetic resonance imaging (MRI) abnormalities in patients with early-onset psychosis (<18 years) compared to community-based controls. 5. People with mental disorders are tested for COVID-19 less often than people without mental disorders, and they test positive more often compared to people without mental disorders.