Fetal Hypoxia and Structural Brain Abnormalities in Schizophrenic Patients, Their Siblings, and Controls

Abstract

STRUCTURAL BRAIN abnormalities are robust correlates of schizophrenia, but their causes have not been conclusively established.^1-3 Neuromotor and cognitive deficits in preschizophrenic children^4-6 and cortical laminar neuron displacement in schizophrenic patients at autopsy^7-10 suggest that at least some of the anatomical changes associated with schizophrenia are neurodevelopmental in origin.¹¹ Genetic influences in schizophrenia are substantial,¹² but the mode of inheritance is complex. It involves at least several genes¹³ and certain neurally disruptive environmental exposures, such as obstetric complications (OCs).^14-27 Of the many types of OCs found to predict schizophrenia, fetal hypoxia has shown the strongest association, accounting for a greater proportion of liability than exposure to infections during gestation, fetal growth retardation, and other obstetric factors.²⁷ Because no study using objective birth records has found that hypoxic OCs are more frequent in the first-degree relatives of schizophrenic patients than in the general population,^17-24 these complications do not appear to be consequences of genetic liability to schizophrenia. It is also unlikely that these early influences cause schizophrenia on their own because more than 90% of individuals who experience fetal hypoxia, even in its severe form, do not develop schizophrenia.^17,18,25,26 Hypoxic OCs must thus act additively or interactively with genetic factors in influencing disease liability.²⁷