Brain Development before Onset of the First Psychotic Episode and during Outcome of Schizophrenia

A circumscribed association between copy number variations and the diagnosis of schizophrenia or autism but not bipolar disorder supports the notion of schizophrenia and autism principally representing a disturbed brain development. Data of multiply affected families show certain brain structural (e.g. hippocampal) changes to also be present in their first-grade relatives with: out leading to psychopathological abnormalities. It thus can be concluded that there exist regional fronto-temporal changes in schizophrenia due to genetically early determined primary vulnerability. The transition of this vulnerability into a prodrome to the point of the fully developed disease is triggered by relevant environmental factors. Hippocampal brain structural changes do not base on neuronal loss, for which reason the underlying mechanism might be a reduction of neuropil and thus a disturbance of synaptic processes or even regenerative mechanisms. Thus, disturbed regenerative mechanisms might be linked to the course of schizophrenic psychosis: the more pronounced the negative symptoms, the more evident the impaired synaptic or neuronal plasticity. Based on initial data we speculate the disturbed synaptic/plastic processes to result from an impaired epigenetic regulation. This could explain how relevant environmental factors (pregnancy and birth complications, early childhood abuse or cannabis abuse) via risk genes might lead to a destabilized neuronal network which in the end could trigger schizophrenia symptoms on the behavioral level.