The biology of schizophrenia as a neurodevelopmental disorder

Abstract

Schizophrenia is a severe psychiatric disorder. Increasingly, research suggests that disturbances in brain development are a major cause of schizophrenia. However, not much is known about the underlying pathological biological processes. It is important to unravel this in order to understand the disease and develop new therapies. That is why Amber Berdenis van Berlekom has investigated specific molecular and cellular processes during brain development that play a role in schizophrenia. Brain development was looked at from different perspectives using both established and innovative translational techniques.

In part 1 of this thesis, research is performed using brains of deceased patients with schizophrenia. The aim here is to investigate changes in the number of connections between brain cells (synapses) and epigenetic differences in the gray and white matter of patients with schizophrenia.

Part 2 focuses on studying very early brain development in relation to schizophrenia. Here cerebral organoids are used, small 3D brain structures grown in a petri dish, which resemble the developing human brain. The research focuses on two environmental factors during pregnancy that are associated with an increased risk of schizophrenia: infection and nutrition.

The research in this thesis has identified specific molecular and cellular features related to brain development in schizophrenia. However, contradictions and heterogeneity have also been found, showing that replication and deepening are of great importance to unravel the biological underpinnings of schizophrenia.