A half-century of participant observation in psychiatry. Part I. Schizophrenia.

In three articles, I discuss the 50 years of my work in psychiatry, in the formula of so called participant observation. The first one is about schizophrenia. I present important events of the pathogenesis and diagnostics in a recent half-century and my attempts to contribute to the research. Significant for clinical description was distinguishing the positive and negative symptoms of schizophrenia. The evidence for subcortical dopaminergic hyperactivity associated with positive (psychotic) symptoms, and prefrontal dopaminergic hypoactivity, responsible for mental deficits and cognitive impairment, has been obtained. Inhibition of the dopaminergic system (blocking of dopaminergic receptors D2) isthe main therapeutic mechanism of antipsychotic drugs. Neurobiological and genetic data also pointed to the role of the glutamatergic system in schizophrenia, which prompted trials of pharmacotherapy. For more than 30 years, the neurodevelopmental hypothesis of schizophrenia, assuming the interaction of genetic and environmental factors, leading to the first psychotic episode, has been the most important pathogenetic concept. In the 1990s, under my direction, neurobiological studies on schizophrenia were performed in the context of positive and negative symptoms and differences vs. mood disorders. Verification of the niacin test, apossible diagnostic aid in schizophrenia, was also made. In the recent two decades, molecular-genetic studies in schizophrenia, also using cognitive endophenotypes and eye movements, have been performed. The association of the polymorphism of various genes with schizophrenia or its endophenotype has been demonstrated, frequently, the first time in the world. In recent years, I directed a team implementing the Polish versions of new scales for the assessment of negative symptoms of schizophrenia.